What is going on everybody, my name is John Hammond and this is the very first hack the box machine video that I'd like to showcase on my channel. I would like to start to do these just before these machines are retired, so when they are retired I can upload them and I'd like to hopefully produce and showcase how I solve some of these. I don't think they'll be the same quality as Ipsak. Shout out to you my friend, if you haven't seen this channel please go check it out, he does some phenomenal stuff. I'd like to try my hand at some of these so I wanted to showcase Help, this machine from Hack the Box. Help showcases the Help Desk software, which is some open source code to actually submit tickets and kind of manage some tech support, web portal, front end that has an older vulnerability and then we can do kind of a simple, cool, at least accessible, easily accessible kernel exploit to Provesk to root. So this machine's IP address is <IP_ADDRESS>, I'm going to go ahead and connect to my open VPN, have the certificate downloaded and ready so I can just roll. I'll go ahead and create a little directory to work with this and you may certainly do the same, I'm going to call this just YouTube Help and then we'll move into that directory. I like to personally take note of the IP address as its own file because I hate when I come back to this machine later, totally forget what the IP address is, I'm honestly too lazy just to go to the website so that's me. The first thing we should do is end map the box, you want to get an idea of what services are running on that machine. So I like to just simply use tack sc, tack sv and I use tack on just to get the end map version and I'll note that as like initial and then I'll paste in the IP address that I'm working on on the box, which in this case is <IP_ADDRESS>. So we'll wait for end map to return its results to us, in the meantime we can start to poke around at some of the services that we would kind of already expect to be accessible. In that case I can assume HTTP will be accessible for us and it is, it's just the Apache 2 Ubuntu default page so there's nothing particularly worthwhile and visible there. We can kind of traverse to some of those other low hanging fruit spots like robots.txt but that doesn't look like there's any results there. But okay, end map came back for us, looks like we have port 22 open which is SSH, we can review these version numbers if we'd like to. We know that okay port 80 has this Apache default page, actually has a port on, actually has a service on port 3000 open and accessible and that it looks to be node. We can take a look at that, looks like hi shiv, to get access please find the credentials with given query, that might be a single page application, it looks like it's working with JSON, that, that JavaScript object notation. So we can put that away for the time being and let's start to look at that actual port 80. What I'm going to end up doing is actually running a full port scan in the background. I'll use tack P, tack and then I'll call that script all ports. And I'm going to end up going to run Durbuster which I tend to like so I'll go ahead and use opt, let's fire up and Nautilus there, Nautilus opt, just so I can open the farm manager. Durbuster is what I want to end up using to enumerate the web pages on this website. So that is HTTP and the IP address. I'll browse to that list that I want to use, I like to just use the medium and I'll drag it out directory list 2.3 medium file extensions, I'll pump in like HTML, SH in case I get some shell shock stuff, text, JavaScript if we wanted CSS, etc. And then the default kind of option seemed to work just fine for me. And I see support and I hadn't seen that before, that doesn't look like a default Apache thing. So I figure let's go ahead and take a peek at support. If I go back to port 80, that original HTTP server, we can move to the support directory and we have helpdesk, helpdesk z looks like a web interface that doesn't really have anything to scroll on. This is the absolute page we can control you to check out the source for the web page. I see some leftover PHP code if client status is not equal to one. No comments or kind of hidden information inside of this text here. But let's poke around. Oh, it looks like more random PHP strings just kind of left floating around. Let's poke around the web page to see what we can do. Can we search in the knowledge base? Do like a attempt for SQL injection if we'd like. We're able to find anything relevant to your search. Let's try double quotes, still nothing. Login. Lost password. An email. We could create like a fake email if you wanted to, like a 10 minute mail or a real mail, stuff like that. I won. Is that an I or a one? I mean, that's a one in the middle, so those clearly have to be I's. That's a valid email address. Don't believe me. Submit a ticket. Knowledge basis where you just were, news, there's nothing there. There's no, doesn't seem to be a means to register. Okay, helpdesk software. I've just, I just moused over the disclaimer here and helpdesk a free helpdesk software that works. Helpdesk is a free PHP based software. It allows you to manage your site support with a web based support ticket system 2015 2016. Doesn't look like that copyright has been updated. But that's the real website. This is, this is the actual official thing. So I wish it would tell me some version information. We can go check out helpdesks on the interwebs. Google that here. Looks like there are some exploits and some information already being told to us here. What does Wikipedia tell me about this? Is there a stable version that's up and available? Is there even a Wikipedia page? I can't track one down for the specific software. That's totally fine. See if we can submit a ticket. If you can't find a solution to your problem, you can submit a ticket by selecting the appropriate department below. General is the only option we have. What's my name? Please subscribe a at a.com. Priority critical. Absolutely. This is extremely important. Subjects can be anything, message can be anything. Oh, it lets me upload something. Okay, so attachments. Well, I guess we could just add like a PHP shell or something. Let's go ahead and create one. I'm going to... Oh, that MAP scan finished. Looks like there was nothing new. We can probably go aggressive on this if we wanted to. Tech A, keep these things running in the background. Let's create just some like shells directory. And let's create a basic PHP shell dot PHP. So that will have our PHP opening and ending tags. And let's just use system of dollar sign get. And those you see as our variable. So that will just run the system function with an HTTP parameter, the get variable that we pass along to it. And that's going to be the C variable. So super simple. That would just print it out, right? Let's see if we can actually upload that. That's in CTF, hack the box, YouTube help. And that PHP shell uploaded. We have to fill out a caption that's kind of annoying each time. But I guess I understand. Submit this, please. Is that not a valid email address? Anything at anything.com. ZQIWV. File is not allowed. Okay, we can do some tweaks on that. We can actually modify it GIF 89A. And then add a semicolon in there to help it kind of look like a GIF file, right? If I were to run file on that, it would tell me, hey, that's a GIF image because that magic file header there, the magic number at the very, very start of the file looks like a GIF file. We can go ahead and try and upload that. Still keeping the extension there. RJ, you, this caption sucks, man. Submit. File is not allowed. Okay, whatever. Let's, we, let's, let's see. When we googled helpdesk, it looks like it already showed us some exploits that might be an option. Let's check on the end map scan. Okay, the aggressive stuff already finished. Running through it. Nothing extremely helpful. That's totally fine. All right. I have SearchSploit installed and accessible on my Ubuntu machine. If you want to get SearchSploit and you aren't running Cali, you can go ahead and get the exploit database, excuse me, exploit database SearchSploit from the GitHub repository. They have it accessible. And it's in their offensive security page here. You can get clone this and then totally run it and work with it. The SearchSploit is the script that you want to end up running. I have that stored in opt. But all that really is, is a command line avenue to access exploit database.com, right? And search for things as you would in the webpage. So I'll use opt exploit DB SearchSploit and it's totally showcasing stuff that I had done earlier to prep. So SearchSploit helpdesks, if we search for just a string of what we're really looking for, we can give it a service name. If you wanted to, a version number, if we had that information, I wasn't able to track that down in the source code. But let's just search for helpdesks and see if we have anything. We have an arbitrary file upload, which looked like we were just trying to do and less than 1.02 authenticated. So we aren't authenticated, we don't have an account or any credentials or users we can log in as. But this arbitrary file upload might be promising. We can go ahead and copy that and move mirror it right to our current location. So let's mirror that here. And now we have this 4030.py. Let's take a look at what that is. I'm going to move it to something that's like a better name, file upload.py. And let's see what that'll actually tell us. Okay, 2016 date. So kind of around that when we saw those copyright messages on the official website, helpdesks less than version 1.0.2 suffers from an unauthenticated suite shell upload vulnerability. The software and the default configuration allows upload for .php files. I think, oh, it does allow for .php files. So when we try to upload it, and it told me that file is not allowed, maybe it was lying to me. I think the developer thought it was no risk because the file names get obfuscated when they're uploaded. However, there's a weakness in the rename functionality of the upload file. Controllers GitHub evolution script. Oh, they actually showcased some of the some of the source code here for that submit to controller dot php in the line. Looks like it's available on GitHub. So we could totally track it down. By guessing the time the file is uploaded, we can get remote code execution. The file name that's stored on the server is set to an md5 hash of the attachments name with time appended to it. The dot in php is to append. And so it's kind of time based, right? It just adds it in with a period added in there and the file extension. So by guessing the time this file is uploaded, we can get RCE steps to reproduce. Go to that's the same form we were just that, right? Submit a ticket, submit a ticket, and action equals display form. Okay. That's it. Action equals display form. Once we've actually selected a department and or anything in the mandatory fields, attach your php shot up php and solve the caption submit your ticket, call this group with the base URL of the installation and the name of the file you uploaded. So looks like that md5 hash of the current time minus, so they're actually trying to figure out an offset or like a jitter, right? Of when, what was the correct second that that was uploaded? Let's take a look at that source code. Because if we're able to track that down. GitHub help desks. Looks like evolution scripts. When was this last updated, man? How old is this January 5 2016? Okay. So this looks like the real thing version 1.0.2. And that's what's referenced in that exploit script. Where did they go? They went to controllers and submit ticket controller, which is the one we're looking for. So let's control F for upload. Upload. Okay. Upload directory. Where is this? Let me just kind of get our bearings first. Display form, which is where we were at in our URL. If it's a confirmation, blah, blah, blah, blah, we're uploads. If we don't have any errors, so if error message is not set, and settings ticket attachment is equal to one, so if we supply the ticket attachment, the upload directory is equal to uploaddir.tickets with a forward slash. That's good to know. What is uploaddir? What is that being set to? Is that anywhere? Try to track down where that might be. There's a way to find inside of the repository, right? There's a way to search inside the repository. I should know these things. In this repository. Okay, cool. Uploaddir. In this repository. Save directory goes uploaddir. Uploaddir. Define uploaddir is equal to root path uploads. And we know it's going to go to tickets. So that's in globals. So let's make sure our script is right. I don't think it is. Help desk base URL, which will be the forward slash md5. So they're not even including it. They're not even including uploads tickets. So uploaddir. Let's say equals that's uploads and tickets plus our md5 hash. So we need to include that in. We'll concatenate in uploaddir. Good. And let's look at that code one more time. Let's see what that says. I think we were in submit to controller and upload. Remove that. If we attach stuff, filename.time is in there. File uploaded is equal to an array that's saved with the file name. That carves out the extension, grabs the file type and everything. Upload file is equal to the upload directory and that file name. So that uploaddir is critical. That is where it needs to go. And if move uploaded file, if not move uploaded file, attachment show step two is equal to true, error message equals error uploading file. If it did not have an error, then it tries to file verify, verify attachment. What does that do? The attachment that we supplied, message code, one invalid file extension or two file not allowed. That's what we saw. We saw that file not allowed. So maybe that verify attachment is doing something odd. Let's check. Verify attachment is the name of that function. They call it every now and again. Okay, this is an includes functions. It says function verify attachment. Verify attachment. Good. So it's getting the parts of the file and the file extension. And okay, that must be testing from a database. If the file type is in the databases, message code two was when it was not allowed. So there must be some file types that they're keeping track of in their database that they don't trust. But if we go back to where we were, that move uploaded file in PHP, that function already does it. Moves an uploaded file to a new location. It's already uploaded before it even checks or tries to verify if it's a valid and trusted extension. So it's already going to be present on the server, right? We can try and find out. Yeah. Okay. So let's, we don't need these arguments. Let's try and let's try and hard code what we would expect the stuff to be. We're going to end up having HTTP <IP_ADDRESS>. And then support is the name of it. It is 121, right? Cat IP address 121. And then the file name, I'm going to keep mine as PHP shell dot PHP. And then the upload directory we're adding in, the current time it tries to calculate, and then it tries to guess stuff within a current range. I think we have everything we need. Hopefully we'll be able to find something. It helped us base URL as it's forward slash and then add upload directory uploads tickets, the MD5 hash that we calculate based off the current time minus a few seconds. It's trying to track it down. And then it'll determine whether or not we found something. Sorry, I did not find anything. Okay. Let's try this. We can submit a ticket. Good old please sub, please sub at please sub.com, please sub, please sub. And let's add PHP shell, HBOHL. Submit. Oh, okay, whatever. Let me, let me start again. If you didn't like my cross-site request forgery token, let's do these. Oh, I need an actual email address. I started to do that in the message U E O R B and we'll attach our PHP shell. File is not allowed. Okay, it should still be uploaded because we just figured that out. Let's run file upload. I did not have it should bangline on that. So let's add one user bin environment Python. And then we should be able to run that. And it needs to be converted. Because we downloaded it. And it still needs arguments. It was testing for those. So we don't need to test for arguments anymore, because we're hard coding them in for our sake. And let's run this takes a little bit of time, right? Because it's going through those 300 seconds. So a couple minutes where it has a window that it could be uploading. And what we don't know whether our time or local time is the same as the server side time. So it has to guess a little bit. But maybe it'll be able to track something down. Okay, tells me sorry, I did not find anything. Okay, so let's go back to the drawing board. Everything looks right. The only thing I'm worried about is that time offset is that time jitter. So if we really wanted to, we could try and add time by going with it starting with like a negative number. Or let's amp it up, let's go like to 500 or something, and see if it'll be able to track something down. So let's go through that process one more time. Please sub, please sub, please sub. Or 5gz and let's upload our PHP shell up PHP submit, it's going and we have 500 seconds in there now. So when we crank on this, maybe it'll be able to find something. And there it goes. Okay, it found something. We have a link and we can go to this. And it has our gif 89. Can we run commands? So I'm going to change my percent sign. I'm sorry, question mark to say these are some variables that I want to pass in and c equals ID. And we get help, help, help, help as the user. Cool. So we have code execution. Now let's see if we can get a reverse shell, right? If we create, we can go get some of those pentest monkey reverse shell cheat sheets. Because that is just going to quickly give us a reversal code that we want. We can actually create one in PHP. We don't need to try and include some of this code in there. We can, we have that large PHP reversal. So it's going to end up being called if we are to create this. So let's go ahead and download this. Let's work with this. If you guys haven't seen this before, this is a more formal and clean PHP shell that if you actually have PHP shell that's being interpreted and ran, where am I going? I'm going to hack the box. It was going into Pico for a second. Sorry. YouTube help. So let's get this in PHP reversal tar or whatever. Go ahead and save it. Because this will allow us to have a reverse shell that's called back to us. And it's a little bit more stable than any of these kind of quick one liner cookbooks that reverse shell like pentest monkey will give us. Let's modify that though. We got to go ahead and extract it. So I'm just going to use the GUI to get that done real quick. And this is really the only thing that we need here. Let's rename this. It's actually, yeah, let's put it in the shells directory. Rename it to PHP shell. So now I want to modify that and actually work with it because we got to give it our IP address, right? It needs to know the reversal needs to know how it can reverse and call back to us, the attacker machine. So this IP and port we need to modify. Let's figure out our IP address. So if config and I'm on ton zero, that's my interface right now. I'm <IP_ADDRESS>. Yours may very likely be different. But let's use that as our IP address and let's change it to 9001. So if we listen on 9001 and we upload that script, once our other script or exploiter attack script finds it, it has already made a request and it should already be invoked. And that way that PHP code will activate and we'll get our shell. So let's upload that and then use the correct CAPTCHA submit files not allowed. We are listening up there. Now let's go ahead and run our file upload script, see if we can track it down, see if we get a catch. And if our reverse shell is activated once we find a correct time match for that file found. Okay, we found the page. We don't have a call back yet. Let's open up that page and see if we get anything. No, we don't. Okay, what's the matter? I must have done something wrong. Did I upload the right script? No, I did not. Because that's still let's give it a new file name. Maybe maybe I need to be cautious with that. Let's say PHP shell call it better PHP shell, right? And I actually want to modify that in our scripts. If you were using the command line arguments, you could just change that while you run it. But better PHP shell is kind of what we need for that. So now let's start over anything.com. And our attachment will now be better PHP shell LZ one HS submit those. It is uploaded even though it tells me file is not allowed. Let's go back to listen. And let's try and run our script again to track down our better PHP shell maybe that file name didn't want to create it because it was already existing or whatever the case may be. We figured you know what? Let's let's play it safe. Let's give a new file name and see what we get. So once we find it, given the time skew, will we get a reverse shell? Okay, that didn't find anything for me. So I must have missed something yet again. Better PHP shell is what we're looking for. Better PHP shell is the correct name. I assess you why we'll submit again. Try that one more time. Okay, so that one got it. Maybe it was little finicky. Maybe I failed the first time. But you can see up top side, I now have a reverse shell. So because I am in Z shell, if I try and use some of those techniques to get a bash shell going and the STT Y raw minus echo, it tends to trip up. So let's go ahead and use bash on this. I'll have bash run. And then I'll use my netcat lvnp to start my reverse shell within bash. We'll check the file upload script to see if we can actually get the callback. It should still be able to reach it. I think it's in that time skew. Okay, now we have a connection. So now I can use the regular Python syntax just as we did before. Now we can background this and use STT Y raw minus echo foreground that. And let's export term equal something like X term. So now I can hit Ctrl L and do whatever I need to do. We have home. We can move into help. And let's use word count to actually see if we can read that user.text file, which we can has 33 characters in it. So we know that is the hash that you could submit and get four points here. But now what do we do now that we are on the box, we kind of want to enumerate and figure out what more we can find out and how we can progress and escalate our privileges. Looks like we have the source code for help, or really that node modules thing that we were looking down. Before I dive into that, I kind of want to run through our lin enum script, the enumeration script, we can run on Linux. I'll move into the temp directory and I'll make kind of a home for myself. You can also move into devshm or shared memory, which is a cool good place to hide if you wanted to make a directory dot sub or whatever for subscribe. You can do that. So if you wanted to drag over lin enum, a cool technique is to use wget or just host it on your machine temporarily. So I created a dub dub dub directory so that I can host files. And then I'll use like Python simple HTTP server so I can pull them down. What I'll do is I'll copy opt lin enum, which I have again, lin enum is download and accessible, you can get it off GitHub if you'd like it, put it in here. And if we need to modify that, we can, we can specify set throw to true or search for passwords or keywords if you'd like to. That's a good idea to do. If you set thorough equal to one, and then keywords equal to something, you can certainly do that. Let me actually go modify that at the very, very top of the script. Let's say thorough equals one. And then I think it's keywords, keyword, you can say like password or something, whatever you'd like here. So now we can go ahead and download that if we start to host it. Let's do Python M simple HTTP server. So it's hosting on port 8000.  Was that right? Let's find out. I have config ton zero. Yes. <IP_ADDRESS>. Port 8000, which is apparently also being redirected on port 80 for some reason on my box. You can see Lynn enum.sh is something that we will show and it can be made available. So that means that on the other remote machine, we can totally W get <IP_ADDRESS>. Let's go to port 8000 Lynn enum.sh. So we'll download it. You can see I got it over on the other side here. And now it's present in this current directory. So what we can do is mark that as executable if we'd like to run it. Go ahead and run it. I like to pipe it to t just to get a log for it log.txt. And then it will go ahead and run through this enumeration script. There's a lot of information that this will dig out. And that will normally help you track down where should I go, what should I look at next? Are there set UID binaries? Are there some odd permissions on some of these directories? Are there other user accounts that are super user enabled or the things that I can run with pseudo that I wouldn't normally be able to do. And that takes some time. So given that this is thorough checks, it will go through everything and take a little bit more time. I don't know if I just lost display here or it's trying pretty hard to do something. Looks like it's trying hard to do stuff. But I'll let this run and we'll pull it out and examine it after I pause the recording. Okay, now that that's done, we have that log that's saved thanks to t. If we wanted to cat that out and view it, we absolutely could. That's still a little bit messy, especially because we won't be able to fit all of that in our buffer. And did I lose some of it? I might have. No, it looks good. But as you can see viewing it in nano kind of sucks because of all those control characters. So if we were to pull this down and we absolutely could, if whatever we wanted to pull up our own Python simple HTTP server on here, can we do that? Will it let us? Let's find out. It will. Okay. So we could very well just W get HTTP <IP_ADDRESS>. Let's get log. Remember port 8000, right? log.text. We'll pull it here. There's a lot of files. There's not a lot of files. It's only one file, but there's a lot of there's a lot of stuff in that file. So we can open that up in sublime text, but that also sucks to look at. So something that I found, at least it sucks because of these color codes, right? Because of those escape sequences, some that I ended up finding was remove or I told it was like strip colors. I saved it. I know I saved it, but there's a way I promise I saved it. Perl, remove colors, escape sequence, and Linux. Removing anti color codes. I saw this. And I had to do it earlier. And some other thing that we were exploring and poking at. But there's a Perl command to straight up rip it out. And there's also I saw someone post like a little little script to do it. I think this one liner should do it just fine. But clear reset said we'll kill it too. So if we were to said on log dot text, that should be perfectly fine now. We can just go ahead and say clean log dot text. My face is in the way. I realize I'm sorry. And now we can access that clean log that no longer has those codes in there. We can totally save that as an alias. And I think that's what I had done. Alias somewhere among these apparently many aliases that Z shell prepared for me. Thank you. I appreciate that. So if you want to review that in sublime text, we had a little bit more scroll and control f functionality, you certainly could. Again, just trying to showcase some some options. If you want to scroll through this, we could. But something that I noted that I picked up on kind of right as I started to peruse through this is that the kernel information 4.40116, it's always a good idea. Just to check if that kernel version is older outdated or actually has maybe some vulnerabilities that might let you do some dangerous stuff. So in this case, it's worth passing it to exploit DB, right? So we had opt exploit DB search exploit. And if we just pass in that in itself, know we got a couple of these Linux kernel noted here and less than 4.4.0116 that might still be worthwhile. So let's mirror this and take a look at it, see what it can do. Maybe that's going to be a kernel exploit that is a privesque. I'll actually run that again so we can see the rest of the description from that page. It says local privilege escalation. So okay, if we have a kernel exploit that works like that, let's take a look at this and see what we have. Subtle this guy. Oh, sorry, we should exploit DB copied over. Let's opt exploit DB search exploit and let's mirror that. So now we have this, and let's move that 4.442 privesque kernel exploit. Sure, this is from ZShell again auto suggesting from some previous stuff, privesque kernel exploit.c 16.04 kernel privesque. Looks like a lot of worthy bites and not a whole lot of comments as to what it does. So okay, we'll determine whether or not we can, whether it is vulnerable or it didn't get a root shell. So let's try it. You can copy and paste this and slip it in the box that way if you want to. Or again, you can just kind of bring this to your www directory. So you can share that and make it accessible from maybe your Python simple HTTP server you're pulling stuff down from. So now back on the box, I'm in that help account, right? We can go ahead and wget just as we had done before and set bradlinlinium.sh. Let's get that, what is it called, privesque kernel exploit. And now we have that in our current directory and we can play with it. So hopefully we can run GCC. Thankfully we can. So GCC will allow us to compile this C source code. Let's call it privesque or something as an output file. And there weren't any errors. So fingers crossed. Let's try and run privesque. And there we go. Spawning a root shell. Now we are root. A bit of a hack. I'm sure there are plenty of other methods and procedures to go away, to go about and solve this. I know that's what I dug out and found. So very, very cool. If you wanted to at this point, you can move to cd root. And you'll see that you have the root.txt which you can go ahead and grab the hash for if you'd like to, but I will not show it to you so you can snag it on your own. And that's that. That is the box. Helpdesk, the port service. Looks like had a little bit of a bug worthwhile and cool that we could dig through the source code and worthwhile that we had to kind of tweak and change that number range and finding the time offset. But we were able to track it down, able to get a reverse shell and then do a little bit of enumeration that normally in practice among other machines and some other stuff we would travel down and other scenarios, we could dig through that linenum.sh output more, but you could totally have just found that kernel version with uname tack A. And you would see that. And if you wanted to give that to search exploit, you certainly could. That would bring you down the same path we did just now. So well, I hope you guys enjoyed this. Hope you guys like this. This was kind of fun, kind of cool. Very, very first time I've been able to share a hack the box box on the channel. Hopefully I'll be able to get it in time before it retires and we'll keep doing some more of these. So thank you guys for watching. Thank you for listening. If you did like this video, please do like, comment and subscribe. There's a link in the description to join our Discord server. I'd be loving to see you. I'm running out of words. I'm bad at these. I'm bad at the outros. If you'd like to support the channel, I'd love to see you on Patreon. I'd love to see you on PayPal. Thanks so much. Until next time.


The capital of Cambodia's southwestern province of Kokong, Kokong City is a small provincial town that rests on the banks of the Kadopah River. The town is about 10 km from the international border crossing with Thailand and Chamomile, and until relatively recently was easier to access from Thailand than the rest of Cambodia due to poor road infrastructure. Now that Highway 48 is paved, the province is easily accessible from Phnom Penh and Sihanook Vail with regular bus services between the cities. Due to its long isolation much of the region is unspoiled and the drive to Kokong City provides some excellent views of the Cardamom Mountains, one of Cambodia's least developed regions. In the area surrounding Kokong has much to offer including mountains, jungles, rivers, islands, a zoo, casino and a lot more. The Cardamom Mountains are covered in pristine jungle with a number of waterfalls that offer a beautiful way to cool down after a long trek. Hiking and mountain biking are popular activities as are water sports such as snorkeling and kayaking. The coast is home to the largest mangrove forest in Asia which can be explored by boat from Kokong City. Trips are also available to Kokong Island, Cambodia's largest island with some of the best beaches in Southeast Asia. For the independently minded there are bicycles and motorcycles for rent in Kokong City giving you the chance to explore the city and wider province according to your own schedule. The city is also home to a large number of restaurants and bars and the riverfront comes alive after 4 p.m. with vendors selling food, beer and sugarcane juice. It's a great place to take an evening stroll, pick up something to eat and relax with a beer or two.


Everybody forced here upping 20 22 score football hobby six bucks number nine random team style The results on screen can be found anytime of late sports cards calm. I did drop you a link in chat Let's get to it every every card ships in this break. However With score having so much vet base. I'm pretty much gonna jump right past all that vet base and not skip through everything's gonna ship for your team But it is score vet base. I'm not gonna show all that. We'll go flip to the rookies though and inserts of course Good luck everybody. Thanks for joining. There's an auto facing the wrong way So I'm gonna show that first. It's a Carson strong rookie auto for the Eagles rookies here God's a Ghost bangles here on the fantasy stars a zappy auto Sam how it played today beat the cowboys a Kareem hunt number to 35 for the Browns Dude, well if this six boxer would take us like like three hours There are there are streams I do that people I mean some people enjoy that totally fine, but Dude, no way no way Not score anyway not score.  That's right, baby. That's what the auto there you go, Elan And a Jeffrey Simmons numbered to 50 gold zone Titans Kenny P auto to six that'd be kind of cool There's some big like autos linger in in this product. You've seen a few will probably see some nice ones in this break So Kenny pick it not you again and a Kevin Byer to 35 Titans Dante Culpepper Vikings auto Like that Knights legend right there. Let's go UCF Kenzie was like, that's why I got my masters. I was like you finished Yeah, I was like I didn't finish Crazy man Jonathan Taylor right side there This one goes chiefs by majority still One more auto coming Maybe another numbered card. I can't remember who do you guys think wins offensive rookie of the year Kenneth Walker, maybe? rookie auto giants Joshua Corbin I Think so too goes Jetsaw majority and James who Williams rookie nice number to 100 for the Lions showcase Here's a lot of cards for you. No way, dude. No way, you know, we would never find anyone do this job All the boom and paper bases go ahead and sleeve and top of the They probably put a stop to that quick Oh Yeah, I'm wearing Pat's hat it's probably the last day I wear one for a while So I was like, you know what I got a rocket today hasn't been a great season, but It was it was a season Now we get picked like 15 or something again Pat Pat's love picking there. Let me tell you Love picking at that spot probably picked our again next year his old bucket. There's Titans Sauce gardener rookie to 100 for the Jets When is the Marjax supposed to be back I'm pretty much coming back next week. They played the bangles Kate Aten bucks rookie auto tits one D on the red zone there you go bucks eight of 20 the brother Ravens they make the playoffs I mean Ravens with Laura dangerous. Thank you to anybody defense got better, too So we'll see we'll see how they do. We'll see how they do. We've got a tough test though Toe the line Devonte Adams Packers to 100 He probably would have won Quarterbacks normally get it easy Plus he's been looking good recently like really good Sausage is heavily favored in like halfway through the season, but it's definitely got closer. Yeah, who's the woollen Woollen, I mean, there's a lot of good defenders He's been up and down, but I mean he was he's been good recently Like that line's been great Mark Ingram the second Saints auto numbered 46 a 50 Hutchinson Carl Aftos was solid furious George Can you pick it base? There's a Bailey zappy bangles on that one Josh dogs definitely solid. Yeah, they just didn't have them long enough Tennessee surprise he still isn't with the Steelers Peer strong junior rookie auto number to 50 pats And a James Lofton Packers numbered to 50. Yeah, I just had a good year He was like the only player NFL history with like five sacks and three picks in one season like NFL history Which is crazy to me That seems like something Ray Lewis would have done before something Jetson majority there Cortland Sutton Baronco's auto to 50 as well a lot of numbered autos in this one. Oh, nice. That's what's up Tennessee players You get him Hedgen Hooker. He's next year It'd be pretty easy to PC UCF players. There's only like one a year if that Yeah, so it's like I was a good game. Yeah, keep it rolling here There's Ricky Otto Jaquan brisker Elway to 100 Broncos. Yeah, if he was healthy Dots and like Almost that almost like touchdown per game and the game and like it if you just count the obviously games he played They shouldn't yeah, they shouldn't Pick it I get it Usually give it to someone that's like Had a really good year You give it to Lawrence. Honestly come back player of the year Trevor Lawrence No, it was like players. I got hurt. Oh, is that is all they do? Yeah, it's like the NFL doesn't have most improved player though Come back I got like Chiefs majority on that one points card wild card random at the end I think Yes, I'm who's gonna be this year Brian Robinson jr. That makes sense Who else would be like a candidate? Other pick it there Yeah, Mike of course, man Yeah, Gary Wilson for sure. I thought he was great. I mean if they had quarterback consistency there We don't matter who it is if anyone was just consistent.  I don't think ever and we pulled two and three boxes so far Harold Andrew to 35 for the Titans that was damaged. I'll send a box and wrapper with this one got peeling on the bottom Titans, yeah, I mean he was there for a couple years big special teamer and he there He was the first team to use them as a running man. He went to the Bears Minnesota's Missy Houston Minnesota had no idea what to do with Cornel Patterson Backwards rainy moths just a base Nice a Kenny Pickett draft insert for a 50 Steelers Yeah, that's what everyone's saying earlier Like if the if the Seahawks lost then it would be whoever wins this is in but now Packers have that tiebreaker JJ Watts six of ten for the Cardinals Barclay Yeah, poor Barclay dude just got drafted by the Giants, which is awful. He's never had a good team around him until like kind of this year It's been hurt. Aiden Hutchinson rookie Otto Lyons Did you know it's how Barclay makes sense? They're both deserving That's like that's an award where you can just give out like they should give out like a few of them I don't know. I feel like if it's there, why not give out a few like it's not like MVP You know like one person should get it but It is about the story because if you come back and play great no one cares So if you're like going to the playoffs to prepare Or if you're like Gino and just bounced around after your whole career after Jets and Giants were just terrible. Who's with the Steelers to? Charleston Rambo Panthers rookie Otto, so you can do his senses is what happens Patterson realizes Can't do it always been a great return. He's one of the best returners. I would say ever I'm not saying the best, but he's one of the better ones of all time Yeah, too today, right Steelers auto Pat Friar muth Johnny Smith Pat's number to 100 Yeah, like it at the time they just don't know how to use them they won't you gotta play two plays a game pretty much Kirk Cousins MVP. Yeah, why not let's do it. I mean MVP is probably got to be my home, right? Commander's Otto Jonathan Allen. You've saved one MVP. I feel like Without it, it'd be terrible Yeah, it's gotta be Luke Keekley to 35 Panthers same with like The Vikings would be really bad without Jefferson. They'd be really bad. I think not really bad, but like they're not playoff good He like legit took over so many games this year He single-handedly destroyed the bills. I mean the bill shot themselves the foot But he also just like took over that game another picket base there There's another like Hey, that was that was the pick right yeah, it's red coming up There's a Jerome Betis auto for the Steelers 20 of 20 The bus It's almost like it was scripted.  Oh Oh Take a while your neck is gonna hurt Does he Yeah, if I had a sign of us, I'll sign at the Donnie Yeah, Hutchinson definitely doing well him and Walker kind of started off because isn't lean and they've both been really good down the stretch Good to see good to see He's been inconsistent, right? Chiefs auto Dante Hall another one of the best returners right there. I mean when I use this sort That's all I would do is listen to whatever podcast your music. I want it to All the time right here. Nothing else That's what Bryson would say As as tough as it is to say the games hurts missed is like just it's like the deciding factor I think Feel like it helped this case because they were like meh without him like his Like the play calling that's why they're watching every evil game to play calm teams so much Yeah, you couldn't run like the read option. I mean, it's a good offense because it's catered to him Like any good offense plays the quarterback strike Nico Collins to 10 for the Texans because I was like Because Someone in here last night was like Getting borderline like really upset because I said my home's MVP overhearts Darius lay jr. Eagles Otto nice sleigh He's had a good season. It wasn't Donnie So in a chat They were like they were like going off just just about it was getting like aggressive and like it was a borderline like spam chat It was so much chat And I was like dude. I was like My homes has that like the numbers like the number one to see them like it's just picking It's like if I'm being ticky tacky, you got to pick one MVP. I'm gonna go my homes over hurts barely Harold Landry Titans Otto, I'd like to see her too. I like to see someone other than my homes My home is gonna win multiple like he's gonna win more I don't know either it's AP right Associated Press They should switch all awards to where like every single player can vote no And they're like say like the cowboys Something I don't think I do something else Matt Ryan's all-time favorite player as a fowl fan that makes sense use your best player your franchise franchise history I mean as far as like what it meant because Dion was there for what five six years Plus I would I would imagine most people are younger It's like my favorite Patriot player won't be anyone before like the Tom Brady era It'd be Brady Brady and then after that rainy boss, I think wrong the jacks. She has a good pick right there. You jack is awesome It still is good doing pretty well with the Ravens I Go bra just because of everything I've seen him do like Saw him do for the Patriots is outrageous Reggie Robertson junior rookie Otto for the Titans Dwight Fredner 35 Colts Yeah, all the Eagles fans are saying Jalen hurts MVP. I get it. I get it. Trust me It is kind of a coin flip if he wins, I will be I'll be happy. I'll be satisfied. I'm not sad I'm just saying if I had to pick Yeah, like realistically and it is literally because he missed games as crappy as it is. He's deserving in My eyes it is a true coin flip of like Yes, yeah, above everybody Like Yeah, but like burrow against art of the season slow and Allen just he has a lot more turnovers on those other guys Yeah, I get that I'm just like if I'm being completely unbiased hot rookies Jalen a wider mire to 35 for the bills Yeah, well, I mean, it's not my home's fault that he's everywhere You like ESPN a bleacher report will show any my home is highlighted at any time. It's crazy. I get that but We also still have to realize that like There's not gonna be another player like this Like he's so unique Now the thing for him now is like how many championships can he win how many circles can he win?   Okay, but also like take my homes off the chiefs like we're having the same exact conversation It's really really even guys.  They're probably looking not super hot Like they're still a good team because Andy Reid coaches up a good team and they have good player personnel this decision-making and all that Bottom line. Let's see. Let's see a chiefs Eagle Super Bowl You're like man if the Eagles make it I do know I want to be playing the chiefs I Get that because last drive of the game ain't nobody I'm taking over my homes currently Even over Brady at this point Ronnie rivers Cardinals rookie Otto, I mean, I think a F almost into a Super Bowl says like as he probably ends up being better than paid I don't think it's automatic, but He's only been to once Talent wise, yeah, but I mean there's been a lot if we're talking about talent all the damn quarterbacks are more talented than Brady He's accurate and he's got a you know, he had decent arm strength when he was younger, but if we're talking like athletic ability Like quarterback talent like accuracy and decision-making I mean this is just making factor into like talent Brandon Graham strip sacks my home's final drive You'd be doing that. I don't know man. My home is probably escaped the pocket Brady couldn't Brady couldn't do it My home is just gonna catch a pass. That's what's gonna happen It's not good man, but both the top of both conferences is pretty stacked Talking legacy or like who's still the best? I think either way I'm going my homes. Honestly. I think I'm going home I Yeah, I like Hertz, but he doesn't have the arm talent the other guys have That's true, that's true. He's got easier path theoretically easier path could change but There's not really Kyler Gordon bears rookie auto got Trent Williams to 100 Niners I'm gonna say my home is just because he is the only one of those guys that has a Super Bowl victory already and He had what a 50 touchdown season in his first full season as a starter. He's the only one with an MVP, right? so far I'm gonna go my home. Just he's already got a lead on all Who do you like more as like a player? I still think Burrow just seems to have the like Like we're sometimes Alan will have a turnover Like we haven't seen that with burrow yet. It seems like Alan's more talent. I mean a lot more physically towns at quarterbacks than burrow burrow is not very mobile.  Caleb LB rookie auto for the Seahawks He is if you had to compare someone too great. He's like the modern break is Except in college. He was incredible I guess he's definitely more physical But he has that same style, you know pocket passer for the most part Yeah, my home was built different go in the homes over everybody the next 10 years Last auto rookie Packers Devontae why it's a 50 McVeigh it seems like he's really like truly 50-50 about coming back And I think it's like he's it looks he's gonna like retire and go into like TV at least for now I mean that could change because he's not even 40 yet. Are you just now for he's like early 40s. Oh No, man depends on that money, I guess He could go he could pretty much go to just about any team and be the head coach right away though Like I'm saying what what what the patch should do is as soon as the off-season starts Which I don't know when tampering starts, but talk to McVeigh right away He won't he won't who would go from LA and like Winning in Southern, California. It's a good in Massachusetts a wild card points random to everybody That's true I mean LA is a basketball town straight up basketball Yeah, four times whoever's up top gets it one two three and four William s w William s w. All right Auto recap here the Devontae Wyatt Caleb LB Kyler Gordon Ronnie rivers Damian Harris Reggie Robertson, Jr. Harold Landry Darius slay Dante Hall Jerome baddest Jonathan Allen Pat Friar Muth Charleston Rambo Aiden Hutchinson quarter L Patterson for the Pats Chiquon brisker Portland Sutton Pierre Strong jr. Mark Ingram Kate Otten Joshan Corbin Dante call pepper Patterson again for the Pats and Carson strong that is gonna do it Thanks again everybody mosaic coming up


Within this project, we find 16 susceptible genes for lupus for the Chinese population. Use polygenic risk score and machine learning to do the prediction. To do the prediction of the disease for the specific population, because we cannot use the genetic data of the European population to predict a disease in the Chinese population. I know someone's opinion may contradict yours. Where's my friend Alan? It's all about your perspective. Who are we and what is the nature of this reality? What's up everyone? Welcome to Simulation. I'm your host Alan Sokian. We are on site in the beautiful Westlake University in Hangzhou, China. We are now going to be talking about Chinese population genetics. We have Dr. Haofeng Zhang joining us on the show. Thank you so much for coming on our show. Yeah, thank you. I'm so excited. It was great getting a nice tour of your lab and what you guys are working on here. Congrats on all the progress. Those of you who don't know, Haofeng Zhang is principal investigator at Westlake University researching bioinformatic tools for the analysis of large genetic data and complex disease. And you can find the links in the bio. All right, let's start things off with one of our favorite questions we like asking our guests. What are your thoughts on the direction of our world? The direction of our world. Yeah, this question is too hard to answer, I think. As a scientist, what we want to figure out is how humans come from and how we go. I think it's such a big question we would like to work on. Yes. Not only on the nature, but also on the society or the human identity, I think. Yes. I don't have an exact answer. Where did we come from? Where are we going? This question is so big. I love the question. Yeah, I always wonder what are some of the main principles that we can embody to help us make sure that it's going in a positive direction. Right. What do you think maybe one of the key principles is? Maybe nature selection. I do research on complex disease, right? So the development of complex disease can be explained by nature selection. Oh, one kind of nature selection. That's negative selection. Yeah. Yeah. Yeah. Wow. So something that humans can potentially do is try and move further away from negative selection where there may be some of the things that cause suffering or disease or things like this and we can maybe move ourselves more in a direction of flourishing away from the complex disease, which is some of the stuff that you're trying to do is help us heal, help us eradicate things like osteoporosis and these types of things. Yeah. Let's talk about the journey. So who were you as a kid and how did you get interested in genetics and science? You mean who made me feel interested in genetics or science? Yeah. I think it's a long story and you know actually my father, he picked this, he helped me to choose my major when I finished my high school and he expected me to be a doctor and actually I majored in clinical medicine and I finished my MD degree in China and but after my MD degree I didn't actually become a doctor, I chose to do research because at that time I did research on genetics of skin disease like lotus and after my PhD, I continued to do genetics but not on skin disease but on the bone disease, bone health, like osteoporosis. So let's talk about as you find yourself getting more and more interested in you know in clinical medicine and then in population genetics and in helping people with disease. You made some pretty serious discoveries along the way and so the MD was from Binzhou Medical University and the Sandong University, Sandong Province in north of China. And then the PhD was from Anhui Medical University and let's talk about the first discovery so we have several of these discoveries that we're going to talk about. This one was about susceptibility genes for systemic lupus and you did this by a genome-wide study in China. So teach us about how you're finding this. So for example we to find this in order to find the susceptibility genes of lupus we need a group of cases patients and a group of controls health individuals and to compare the allele frequency of these two groups. If a SNP has a very different allele frequency between these two groups, we obsess that this SNP is associated with the disease. And within this project we find 16 susceptible genes for lupus for the Chinese population. Okay so you're given a population-wide genetic database and how many samples were in this one? Maybe a couple? How many samples did you have in this one? You mean this project? The lupus project? I think it's 3,000. Okay so you have 3,000 and so some of them have lupus. Yeah some of them have lupus. Almost a thousand had lupus. Yeah and 2,000 did not. And then what you were doing was you were looking at how did you find the you said 14 genes? 16 genes. 16 genes had the strongest susceptibility to having a SNP in them which is a variant in the genetic code. So an allele, two alleles for one SNP and how did you identify these 16 genes? You know that in the whole journal type, typing data, we have less than a million SNPs right? And we test this one million SNPs one by one, test the association with the disease one by one and find 16. Not exact 16 because the SNPs they have LD that means one SNP, if one SNP exists then another SNP will exist together. That's LD but these 16 SNPs they are independent SNPs. They have no LD with each other. And then you find out these areas of variants that are similar for people with lupus and that people without lupus the other 2,000 don't have the same variants that the ones with lupus do in those 16 genes. Actually it's the frequency difference between cases and controls. Frequency difference. A little frequency difference. Actually in controls they also have the allele but the frequency will be much lower. In cases the frequency will be much higher Interesting. Yeah let's let's let's the SNP. The SNP means the SNP didn't mean that it didn't mean it didn't exist in controls. It did exist in controls but a little the frequency much lower. Interesting yeah okay okay okay so the allele difference the allele frequency difference in the lupus was higher right okay okay and lower in the control that you have lupus okay okay interesting okay and then so then then it was our I'm curious for other discoveries as well is allele frequency difference a pretty good indicator of what a potentially a discovery of a variant in the disease is? Yes that's what we want to say that the allele frequency difference between cases and controls is a pretty good biomarker yeah yeah it's a biomarker yeah one of the top biomarkers is a allele frequency difference right interesting so when you get actually the SNP is the biomark the SNP is the biomarker yes and there's a there's a greater frequency of SNPs in patients with lupus yeah in this case yeah so for all of us that are getting our genome sequenced that we're we want the some of the things that we want to care about is our our allele frequency difference we want to that's that's something that's a big biomarker for okay yeah that's what we want to say let's let's let's uh we we let's we how we choose the SNPs how we choose the SNPs we choose the SNPs with very different uh allele frequency between cases and controls let's we choose these 16 SNPs they have very different allele frequency difference okay yeah so there's 16 specific SNPs that had the greatest allele frequency difference yes okay and then you hypothesized that those were the 16 SNPs that were related to the difference between healthy patients and lupus yes and it was correct like yeah like cool cool okay okay okay so so then it could potentially be that identifying SNPs in genomes and looking at allele frequency differences between healthy populations and the disease populations is one of the biggest ways to identify disease right yeah no okay and was now what were you doing in this next discovery discovering the north south population structure of chinese han population what is tell us about this uh in this project we include uh samples from ten different chinese population uh ten ten chinese population uh provinces provinces uh distribute from north to south we select ten province from south to north and to see the population structure um the population structure uh differences between these ten provinces and we we we discovered that uh there are two dimension distribution of the genetic structure yeah uh let's that means um um in north from uh liao ning that's a province from uh north east from liao ning to sandung them to uh uh hung the zhejiang them to guangdong the geography uh came proxy the genetic uh structure okay so so again you had a sample of yeah how large was the sample of it's six thousand six thousand from these ten uh provinces yes and five were in the north and five were in the south or um i think uh yes um also they have uh six thousand them i think is two thousand from north two thousand from south and also two thousand from middle middle yeah interesting yeah okay and then um when you were analyzing the genetics of those um six thousand what were you looking for to determine the difference between north and south han chinese because we we have already done the whole journal journal typing and this can provide the information of all the genetic information of all these samples and we do we conduct an analysis called principal component analysis this can identify the uh the the genetic component of the populations of the samples a principal component analysis yeah principal component analysis that's pca pca yeah it can identify the the specific genetic differences between yeah because we can use the principal component to uh the the value of the principal component to compare the values of these samples okay okay yeah okay and and the the big um the big difference is that you said there was some sort of a of a distribution between the clear distribution between who was south yeah yeah yes yes if we have a very big reference uh we we have uh ingredients from each uh province uh and the the sample size is big then we can build a this kind of reference yes and a new one come come here we can sequence them and to see which province he's come from yeah yeah yeah and then there was a postdoc that you were doing at McGill university that was in human genetics right and when you were doing that four years you made another discovery in 2012 to discover the susceptible genes for osteoporosis yes okay and this was fracture and thickness of bone in the Caucasian yes okay so explain this one to us as well uh it's uh it's uh it's osteoporosis related to trade a related disease right um the the final outcome of osteoporosis is fracture yeah uh so the just the just tg is the same as what we have done for the skin disease we also the design is also the same uh group of cases and a group of controls and to to see the uh the the uh a little frequency difference and for this project why um this this project uh published in nature because uh we find the rare genetic variant because in in in um the rare genetic variant is hard to find because they are rare you you know in in um for example in 1000 samples maybe the mutation only present in only one individuals so it's very rare it's hard to find so we find the rare genetic variant for osteoporosis yes yeah how out of a thousand samples are you able to find just one of the rare genetic mutations um this just example yeah actually it's not only one maybe several okay yeah because we do the genotyping we do the sequencing and the genotyping we know the the the the the we know the allele of each the uh interviews we know the allele of interviews yeah and then you find and then you know the ones that have osteoporosis and you see which allele variants yeah the rare genetic variant the rare genetic variants associated with osteoporosis yeah and versus the rest of people don't have that right and so then you're able to target that and say that that's probably the right and you maybe look at other people with osteoporosis and see that they have the same right okay right okay okay so then in 2015 these have the these kind did these happen at the same time the 1000 talents program by the chinese government and also the um the uk 10k project which one happened first the uk 10k project first yeah the because the uk 10k project they start from uh they started from 2010 and finished in 2015 so we published this paper in 2015 yeah okay and then in that uk 10k project in 2015 you found the rare variants for bone mineral density yes okay so you were teaching me about this um bones are made of calcium uh bone mineral bone mineral is made of calcium yes and then there's bone marrow inside that we were talking about as well yeah belief has a lot of the stem cells yes okay so the bone mineral density and this is in uh grams per square centimeter yes if it's too low you have higher propensity for osteoporosis yes higher fracture and fracture yeah which leads to fracture yeah bone weakness yes leads to fracture yes um yeah so how did you find out that that this density of of bone mineral was uh that you could figure out based on genetics density of bone minerals uh um yes because yes or no because bone marrow density have a very high habitability uh it's about from uh 15 to 85 percent um 50 to 85 percent yeah yeah of high habitability that means 50 percent to 85 percent of the bone mineral density variation can be determined by genetics yeah yeah but of course it's also influenced by uh by by by the environmental factors yeah so um so the answer is yes for no okay yeah okay so then um you were identifying in this uk 10k project specific is it again a allele variance yes yes for osteoporosis yes bone mineral density being right okay okay became the professor at hanjo normal university for two years in 2015 2017 and what were you doing when you were there um teaching genetics um part of my job is teaching also um research work and research yeah and research your papers have been cited 3400 times that's massive yeah it's a lot of citations yeah that's the total citation of my rotation yeah yeah yeah that's so cool and then um west lake university in march 2017 so you've been here over two years now right and you've been approaching two and a half yeah that's really cool it's now two and a half yeah yeah it's two and a half yeah and so and this has been slow growth process of of acquiring now 10 lab members there's seven phd students working at the lab yes and now this is going to be this deep dive there's so much cool stuff here so bioinformatic tools for the analysis of large genetic data and complex disease so you were teaching me about this you said that right now we have this issue with genetics where most of the whole genome sequences in the world are europeans yes yes and so the the reference that we have of these 30 million variants are are made for analyzing european yes yes so there's this idea of genetics for all right where you can have like you have 1.4 billion people in china another one point almost four in india right and you know so the idea is that can you make a a whole genome sequence reference of these 30 million variants for chinese people yeah and for indian people yes and for all these different countries in the world yeah so it's not just for european people yeah i like i love this so then you had this idea of having the west lake bio bank for chinese right w bbc right so teach us about why you're doing w bbc where you guys are at teach us about it yeah just like you said that most of the genetic data and now generated most of them are uh on the european populations so if we would like to do a prediction of disease we need to um derive the effect from the uh specific populations like if we want to predict disease for chinese population we need to derive the effect from chinese population so uh we that's why we want to do this wet lake bi bank for chinese to um this bi bank can be uh um can can produce a lot of data and to produce a lot of effect which can used to predict the disease i think yes okay so as we have more of these uh bio banks happening for different countries around the world you guys hopefully um going deeper into the chinese bio bank then we can better understand the formation of complex disease and we can help people live healthier yes their lives yeah okay so um where yeah let's talk about where you guys are at with that so um you've had you you're working with universities yes and so universities um are um are the blood samples from universities yes so do you guys take their do you guys take the blood samples to sequence it yourselves or do they sequence it and give you the data how does yeah um we take those samples and we uh sent out to companies they have us to sequence them got it and they return the data to us got it yeah okay so the university the blood from the universities goes to the company sequencing companies which then give you guys the data and then when you guys you have how many total um sequences 4500 plus the 6000 so teach us about the total right it's about 10k right 10 000 yeah yeah and four and a half thousand are whole genome sequenced and then six thousand are whole genome genotype yeah right okay and then now how are you then um studying the genetics of bone mineral density in this sample that you have so you're looking for the allele variants of osteoporosis yes okay yes um so the stress the suggestion is a little different from my previous study um in this study we didn't care about which gene it's associated with the disease we use the whole genome uh data to to do the prediction then we use the uh machine learning method to do this prediction also the uh polygenic risk score yes use polygenic risk score and machine learning to do the prediction okay okay so when you talk about polygenic risk score and machine learning apply to whole genome sequencing what do you find that gives you the understanding of osteoporosis uh in fact this project is still ongoing yes right um i uh just start my uh the laboratory in west lake for two years yes and it takes me a lot of a lot of time to collect all these samples and we just start this project hope hopefully we can uh gate uh work good results to help to predict the uh osteoporosis for the Chinese population yes yes i love the big vision that you have with it and this is one of the things about science and it needing to be better well funded and also have more world-class research places like west lake pop up because then you can have more scientists that are doing these long processes that take time that then it can have better computational resources right and better genetic data bank resources all this type of stuff to help you guys move the pace faster in scientific discovery right okay so one out of every thousand references variants that we have is genetic variants one out of every thousand genetic variants that we have is going to be some sort of a potential formation of maybe a disease maybe yeah it's possible yes okay okay so you can be more susceptible to developing the disease but not develop it right you're right yeah okay okay so i can have um high allele frequency difference and be susceptible to developing the disease but not develop yes so then it's okay to have um in a health some people in the healthy population have high amounts of variants but they don't develop the disease yes okay and then there are other people that yeah because this this is a probability it's a probability yeah this is a probability yeah these people who uh carrier this allele they are most susceptible to the gene to the disease but maybe he he didn't develop develop this disease at the end oh they died before they developed this disease yeah yeah i have let's say an uh an uh allele uh variants that um gives me maybe a 20 probability to develop a disease yeah something like that so it's like one in five it's a little bit lower so i don't have it yeah but you could go the other way and say that oops this fifth person got it the disease because they yeah yeah you can have and you can have different variants probability probabilities yes that's why we would like to do the prediction the prediction also a probability so if if a person who uh have uh at a higher susceptible to the disease then we for example osteoporosis then we can uh do the intervention of these uh patients or individuals yes to um to uh prevent the final outcome yes let's talk about um the interventions because if um i do have the allele variants and a high probability of developing a complex disease um what are some of the best things that are recommended for people right now for like osteoporosis yeah so for the osteoporosis um this uh i think the three three main factors can affect osteoporosis the first one the major one is the genetic fact right we already talked a lot the second one is the uh nutrition the third one is the exercise so um so the genetics now we can we we cannot for for the complex disease um it hard for us to edit it to edit the genetics the the genome so we can uh do uh modify the other two factors the nutrition and the exercise yes yeah so then the behavior changes towards better nutrition and more exercise can help um decrease the probability of developing a osteoporosis and then also down the line it is possible that we can go with something like CRISPR potentially yeah go and make the genetic edit that needs to happen in order to um also fix the disease of the osteoporosis yeah it's uh because this is a complex disease it's a complex trait yeah um it's not a single point yeah it's not a single point yeah uh uh where and can we're talking yeah like dozens yeah points right variants so if we go and change one of that right more than that right if we go and change all of those there's potentially effects five years ten years down the line that we're like oops yeah that could be the problem yes okay yeah right this is why biology simulations are very important because if you can simulate what doing those who knows 30 points of of change are it's forward to make it a healthier individual without the complex disease of osteoporosis can you fast forward 20 years and see if the person yeah yeah okay and can you do that millions of times to make sure after right there okay right yeah yeah right these are some of my favorite things these simulations okay because um hopefully we can get to the point where we can do it better and better um because then people can live healthier and not have to yeah experience complex disease right okay so um also uh at the lab is uh a bunch there's people doing different things here you have you have people looking at the genetic variants in the chinese population you have um a recent study that was finished on alcohol and blood pressure yes which i found to be very interesting um there's a very there's a very specific allele variants yeah for people that can not get drunk fast and people that get drunk too fast yeah which is a very interesting study because then some people will know it's like why do i keep drinking one glass of wine and i'm drunk already yes yeah stuff like that yeah because then you can know that it has to do with your genetics like it's very interesting right and the other ones are like i drink a whole bottle and i'm fine yeah why yeah yeah yeah sometimes we yeah it's cool to know that biology um and even something um like allele variants and this was only at a single point yes it's a single point yeah yes wow and um for for those that um are really interested it's rs 671 yeah rs 671 yes for those that are very interested in that variants that's cool and that was in a a sample of 2349 hanzhainese yes yes if it's a gg you can drink like like if it's a a you're gonna have trouble with right drinking a lot yeah yeah okay for myself i already genotype this my is a g okay so you're middle yeah i'm in the middle but um i cannot drink a lot so yeah and then um and there was also another interesting cultural aspect too with women where women are generally in China not drinking so much so um a lot of them in this study were yeah yeah even yeah if they had gg for drinking a lot they weren't drinking anyway right right yeah and then um another one is doing epidemiology of peak bone mass of chinese obviously so we actually actually we had a we had a good conversation about this before we started too um the number was um the number was quite high it was uh it was 1500 uh total mass of skeletal calcium in grams was 1500 for men between the ages of 20 and 40 yes so so basically that's the peak bone there's the peak bone yeah so so basically when you're a child um your uh total skeletal mass in calcium in grams increases very fast yes until you're like 20 yeah and then it like peaks around that 20 to 40 range like for men it's 1500 grams and for women it's closer to 1200 grams and then after 40 um both men and women start dropping yes and then women have a more significant drop because of menopause yes yes yes i found this to be so so interesting and because you were mentioning this earlier too there's a 50 to 85 percent heritability right of this right um so it's very likely that if your um if your parents have a lower amount of total skeletal calcium mass that you as well will have lower and so then i was asking you about this too is like okay so when you're doing this i mean is it possible that we can find um as you guys are doing this this uh dive into the epidemiology of peak bone mass of chinese is it possible that you can find um specific uh variants um for people that have a higher peak bone mass yeah versus ones that have a lower peak bone yes yes yes yes let's one of our design to in order to find the the genetic variant for the peak bone mass and why we want to do this is um you know most of the drugs treat on osteoporosis nowadays they are the drugs trying to slow down the loss of bone um if we can find a gene or a pathway who uh which is a determinant of the peak bone mass maybe we can find a drug target to increase the bone mass yeah because most of the drugs now they are their target is to uh decrease the bone loss yeah to slow slow down the bone loss yeah yeah interesting so we're in a sense we're fighting the osteoporosis with trying to slow down the uh the bone law the bone density loss yes and we could come up with another solution yeah which is targeting uh more bone density yeah to increase the bone density interesting yeah but we have to find the variants right first right and then we have to target the drug at um those variants yeah and figure out how to increase them right interesting so in a sense there's for only probably for a lot of complex disease there's a couple ways to handle it yes um and many of the ways we handle complex disease right now is like how do you take in uh molecular compound that uh usually affects more than just uh the targeted yeah area and uh it um fights it in a specific way and maybe there's ways that we can take something that um enables us to fight it in a more optimal way right so discovering those pathways to for more optimal combating complex disease yes yeah yeah like that okay so then um also using machine learning to predict the height of chinese men yes so then do you do you have um any like ideas about like these these are complex things like this is a not yeah probably yeah this is single right yeah this is another complex trait yeah um you know because we have this population and this population is at the main age of 19 and we have the height measurement we also have um the weight and other measurement and we would like to build a model to uh predict from genomics to height and if we have this model then new new uh bomb uh comes out if we then if we we uh have their DNA we can predict the height that they are 19 age yeah yeah yeah that's really interesting yeah yeah yeah yeah so yeah and as you get more and more of the um genetic samples you can have a greater greater accuracy right of the height right yeah interesting and height is more likely to be accurate than weight right yeah right weight is so um variable variable about what they eat how often they exercise all this kind of stuff yes but height you're pretty much going to end up being that yeah yeah interesting okay um interesting too that um for probably for those that are you know that are watching that are thinking well um there are likely lots of other scientists um around the world that that watch the program and um especially also you know PhD students etc um uh postdocs whatnot that are just trying to figure out um how do I leverage computational power onto um genetic data sets um and to find unique insights and so you know like you know you guys here if you guys want to you know come and look for opportunities westlake has lots of unique opportunities where they're looking for um people to do PhDs and postdocs yeah and uh be able to join a really powerful yeah of course of course yeah yeah I wonder you know once we leverage more computational power on um on challenges like this what unique insights we'll find like well how many you know variants determine height and where are they uh that type of stuff okay and that's just height that's one thing then there's you know there's all of the other well what about you know this one's really tough but like IQ that's yeah yeah yeah right that's a really interesting right right yes like is it possible to you know to predict something like that uh but that also determines a lot if you're sitting there doing uh like you know too much studying yeah yeah too much uh uh distractive material even if you had a higher propensity for IQ it might have um been lower yeah but uh it could also be the opposite where if you read a lot and if you worked really hard yeah um you could have you end up a little higher too yes yeah yeah this is this is all so interesting to me leveraging computational power on on genetic data yeah and then um okay so also there's um a surname and geography study and an ancestry and geography oh yes yes okay so what are you guys looking at there uh we um get our surname from our father right and we also uh get our uh white chromosome from our father and so we would like to see um um um a person who have the same surname of of me like Zen we I want we want to see how similar of our uh genome is between us yeah if we we have the same surname how what what proportional uh of the genome we share together yeah yes yeah so depending on your last name if it's the same you may have a higher no we cannot say that because uh for example uh uh people with the same name of Zen like me and other people who have a same name of Wang but I have uh more genetic similarity with them yeah yeah because oh these people who uh name of Wang he is my cousin or dancing then we can we may share more uh genetic yeah yeah yeah yeah okay interesting point yeah maybe someone born in your province near you with the different last name you have more in common with than someone with the same last name but from the south part of China yeah from the north part something like that yeah that's the interesting thing we want to do yeah yeah the research yeah yeah and then I was asking you about this too um the uh metagenomics in this in this sense you guys are doing proteomics yes on the 6000 yeah and then what do you guys want to find with doing metagenomics studies on the data researchers would like to link their microbiota to uh different disease also I think is to um um trying to do the intervention yes of all this disease so what we want to do is to link the microbiota to osteoporosis and to to see um because we we have genetic data we have um if we have another other data we can I think we can uh explain more of this disease right yes yes yeah yeah so the more you have these metagenomic data's proteomics microbiota all this type of stuff sequenced yeah you can potentially uh come in with a intervention through the microbiome yeah yeah you can do different interventions yeah yeah interesting to tackle complex disease yes your process and more okay and then what do you think that you know having these bio banks um what will be the big thing like if we have the 30 million reference for the variants um in chinese and then we do that for indian and african and you know your europeans already done south american blah blah blah you just keep going yeah what insights are you most excited about that bringing for chinese and for all these other populations around the world um let's the prediction of the disease to do the prediction of the disease for different for for uh for the specific population yeah if because we cannot use the genetic data of european population to predict uh disease in chinese population yeah yeah how much um overlap is there with um european population genetics with uh chinese is there you know out of these variants out of these 30 million variants yeah how many yeah in fact most of them are overlap most overlap yeah most of them are overlap well i mean um for the calmer variant most of them are overlap for common variants yeah for the rare uh each each population have their own unique rare genetic variant interesting and um for but uh like is osteoporosis rare yes no no no it's not no i mean i mean the i mean the rare genetic variant not the not the rare disease yeah yeah oh rare genetic variants yes most common genetic variants overlap yeah okay and rare genetic variants don't overlap yes what percentage do you think is common versus rare the more bigger of the uh population than the more rare genetic will be found larger populations have have more uh rare genetic and more rare genetic variants yes what would an ideal tool be like let's say 50 years 100 years down the line in the future what would your ideal tool be like for doing the most advanced bioinformatics um you mean the tools developed to do the um to analyze the genetic data to analyze genetic data and then to deal with complex disease yes to augment humans yes make us better yeah what would that tool look like 50 or 100 years down the line uh um yeah because the the genetic field moves fast um i think one thing is the prediction yeah the prediction tools to use a specific population to predict uh disease for that specific population yes so i think this tool can be a good one predicting disease yeah predicting disease but of course we need the reference we need the reference to do so yeah okay okay so it would be maybe something that's all in one that gets the genetic data that does the analysis that predicts the disease that gives recommendations right the whole kind of this okay yeah okay how do you think we can inspire more people around the world to work together if the data can be shared between um um research group or research group within one country or in different country yeah then i think the problem is the data sharing i think yeah yeah i like that answer so much we have a big problem with data silos across the world um across the big tech companies across the big governments across the medical institutions the research institutions etc and so yeah if we can more easily share data to provide unique insights yes yeah people's health into their education into their well-being right you know that's like let's figure out how to maximize doing that soon yeah i like that okay for young people what's an important skill that they need to know as we go into the exponential technology age for young people um young people at at which age young people in general today um i don't know if i can group at the young people um let's say those that are still in the school system yes school high school or yeah sure okay i think this question has different kind of answers in different country or in um with different cultures yeah right um because of education it is very different between like china india and the us right so yeah yeah is there something that you think china india the us and other countries around the world do you think that there's something that young people can learn that makes them just stronger for the future the the the basic thing is i think they should well educated right i think yes mm-hmm yeah i agree yeah i agree mm-hmm it's hard to say what is the best education system yeah we have act sat gaokao we have all these yeah systems but what about social intelligence and what about spiritual intelligence what about solving the sustainable development goals of the united nations mm-hmm so it's hard to exactly say what that is but i agree that the education yeah what do you think is the meaning of life oh so this this is another big question uh we should make our life more happier we should let our parents live better to we should have a happy family mm-hmm to provide a good education to our kids if we were overloaded by our daily life we maybe we have no time to think about the meaning of life right because we don't know the world after we die right so we should live a bad life when we are alive also think about our family of parents and them i think yeah this is exactly why we ask the question because if we don't think about why we're here and what the purpose of this is what my purpose is what is the nature of this reality that we're in then we forget these very first principle yeah questions yeah right right and then we just go and just do whatever right sometimes the economy or sometimes politics or media or whatever determine our life instead of right ourselves yes yeah yeah but in daily life we we always think about this the politics the economics that the also the project I need to finish right let's um if we overload by our the least kind of things maybe we forgot to think about the meaning of life yeah yeah exactly I appreciated how during the conversation we were both a little bit hesitant about the future of genetic engineering because to be to have this seventh generation principle so you have to think about what am I doing right now and how is it going to affect seven generations down the line yeah yeah so that you don't just say do that genetic edit and see what happens hope it's all good no so doing like biological simulations all these types of things to make sure that what we're doing is uh going to be healthy is very important um do you have uh that mentality that you carry with you about genetic engineering you're a little bit more conservative um about it um yes I I think uh scientific society they all I think they all have conserved attitude to this question to this yeah to the genetic editing yeah yeah yeah that I am starting to feel that more and more it's important to have open-mindedness uh and a little bit of liberalness to be able to run the experiments over time yeah and find out okay the healthy ones are are good that so we can start maybe implementing those but to um be very also um cautious about what could be some of the long-term effects of incorrect decisions right um can be very bad yes yes what do you think is the role of love in our world we care about our parents we care about our wife we care about children's yeah love is everywhere yeah do you think that this is a simulation I don't know I I don't know how to answer this question so yeah what do you think is the most beautiful thing in the world love why um because um because love is everywhere and love makes us care about this world care about people's around us yeah yeah with that more love we care more about each other in the world yes yeah huvong thank you so much for coming on to our show thank you thank you it's such a pleasure thank you thank you yeah incredible discoveries thank you thank you yes we're super looking forward to all of the next advancements that you're doing in population genetics and complex disease thanks everyone for tuning in we greatly appreciate it we'd love to hear your thoughts in the comments below on the episode let us know what you're thinking have more conversations with your friends your families co-workers people online about population genetics and about complex disease about all these other topics that we talked about on the show about genetics for all about creating these bio banks in china and in all these other countries around the world making better tools for analyzing these large genetic data sets the different very variants and genetics that we were talking about have more conversations about solving these complex diseases and living more healthy and happy lives also support the artists the entrepreneurs the organizations and leaders around the world that you believe in support them and help them grow you can find all of our links below so you can continue doing cool things like coming on site to beautiful places like wesley university and interviewing some of the great principal investigators here and go and build the future everyone manifest your dreams into the world we love you very much thank you for tuning in and we will see you soon peace that's a wrap good job good job thank you good job okay