Cell Death Discovery, Published online: 10 July 2025; doi:10.1038/s41420-025-02615-5
The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields)
Michigan may be best known as the birthplace of the American auto industry, but its innovation legacy runs far deeper, and its future is poised to be even broader. From creating the world’s largest airport factory during World War II at Willow Run to establishing the first successful polio vaccine trials in Ann Arbor to the invention of the snowboard in Muskegon, Michigan has a long history of turning innovation into lasting impact.
Now, with the creation of a new role, chief innovation ecosystem officer, at the Michigan Economic Development Corporation (MEDC), the state is doubling down on its ambition to become a modern engine of innovation, one that is both rooted in its industrial past and designed for the evolving demands of the 21st century economy.
“How do you knit together risk capital founders, businesses, universities, and state government, all of the key stakeholders that need to be at the table together to build a more effective innovation ecosystem?” asks Ben Marchionna, the first to hold this groundbreaking new position.
Leaning on his background in hard tech startups and national security, Marchionna aims to bring a “builder’s thinking” to the state government. “I’m sort of wired for that—rapid prototyping, iterating, scaling, and driving that muscle into the state government ecosystem,” he explains.
But these efforts aren’t about creating a copycat Silicon Valley. Michigan’s approach is uniquely its own. “We want to develop the thing that makes the most sense for the ingredients that Michigan can bring to bear to this challenge,” says Marchionna.
This includes cultivating both mom-and-pop businesses and tech unicorns, while tapping into the state’s talent, research, and manufacturing DNA.
In an era where economic development often feels siloed, partisan, and reactive, Michigan is experimenting with a model centered on long-term value and community-oriented innovation. “You can lead by example in a lot of these ways, and that flywheel really can get going in a beautiful way when you step out of the prescriptive innovation culture mindset,” says Marchionna.
This episode of Business Lab is produced in partnership with the Michigan Economic Development Corporation.
Full Transcript
Megan Tatum: From MIT Technology Review. I’m Megan Tatum, and this is Business Lab, the show that helps business leaders make sense of new technologies coming out of the lab and into the marketplace.
Today’s episode is brought to you in partnership with the Michigan Economic Development Corporation.
Our topic today is building a statewide innovation economy. Now, the U.S. state of Michigan has long been recognized as a leader in vehicle and mobility innovation. Detroit put it on the map, but did you know it’s also the birthplace of the snowboard or that the University of Michigan filed more than 600 invention disclosures in 2024, second only to the Massachusetts Institute of Technology, or that in the past five years, 40% of the largest global IPOs have been Michigan built companies?
Two words for you: innovation ecosystem.
My guest is Ben Marchionna, chief innovation ecosystem officer at the Michigan Economic Development Corporation, the MEDC.
Ben, thank you ever so much for joining us.
Ben Marchionna: Thanks, Megan. Really pleased to be here.
Megan: Fantastic. And just to set some context to get us started, I wondered if we could take a kind of high-level look at the economic development landscape. I mean, you joined the MEDC team last year as Michigan’s first chief innovation ecosystem officer. In fact, you were the first to hold such a role in the country, I believe. I wondered if you could talk a bit about your unique mission and how this economic development approach differs from efforts in other states.
Ben: Yeah, sure would love to. Probably worth pointing out that while I’ve been in this role for about a year now, it was indeed a first-of-its-kind role in the state of Michigan and first of its kind in the country. The slight difference in the terminology, chief innovation ecosystem officer, it differs a little bit from what folks might think of as a chief innovation officer. I’m not all that focused on driving innovation within government, which is what some other chief innovation officers would be focused on around the country. Instead, you can think of my role as Michigan’s chief architect for innovation, if you will. So, how do you knit together risk capital founders, businesses, universities, and state government, all of the key stakeholders that need to be at the table together to build a more effective innovation ecosystem? I talk a lot about building connective tissues that can achieve one plus one equals three outcomes.
Michigan’s got all kinds of really interesting ingredients and has the foundation to take advantage of the moment in a really interesting way over the next decades as we look to supercharge some of the growth of our innovation ecosystem development.
My charter is relatively simple. It’s to help make sure that Michigan wins in a now hyper-competitive global economy. And to do that, I end up being super focused on orienting us towards a growth and innovation-driven economy. That can mean a lot of different things, but I ultimately came to the MEDC and the role within the state with a builder’s mindset. My background is not in traditional economic development, it’s in not government at all. I spent the last 10 years building hard tech startups, one in Ann Arbor, Michigan, and another one in the Northern Virginia area. Before that, I spent a number of years at, think of it like, an innovation factory at Lockheed Martin Skunk Works in the Mojave Desert, working on national security projects.
I’m sort of wired for that, builder’s thinking, rapid prototyping, iterating, scaling, and driving that muscle into the state government ecosystem. I think it’s important that the government also figure out how to pull out all the stops and be able to move at the speed that founders expect. A bias towards action, if you will. And so this is ultimately what my mission is. There are a lot of real interesting things that the state of Michigan can bring to bear to building our innovation ecosystem. And I think, tackling it with this sort of a mindset, I am absolutely optimistic for the future that we’ve got ahead of us.
Megan: Fantastic. It almost sounds like your role is sort of building a statewide startup incubator of sorts. As we mentioned in the opening, Michigan actually has a really interesting innovation history even in addition to the advances in the automotive industry. I wondered if you could talk a bit more about that history and why Michigan, in particular, is poised to support that sort of statewide startup ecosystem.
Ben: Yeah, absolutely. And I would even broaden it. Building the startup ecosystem is one of the essential layers, but to be able to successfully do that, we have to bring in the research universities, we have to bring in the corporate innovation ecosystem, we have to bring in the risk capital, et cetera. So yes, absolutely, startups are important. And equally as important are all of these other elements that are necessary for a startup ecosystem to thrive, but are also the levers that are just sitting there waiting for us to pull them.
And we can get into some of the details over the course of our chat today on the auto industry and how this fits into it, but Michigan does a lot more than just automotive stuff. And you noted, I think, the surfboard as an example in the intro. Absolutely correct. We have a reputation as Motor City, but Michigan’s innovation record is a lot weirder in a fun way and richer than just cars.
Early 20th century, mostly industrial moonshot innovation. So first paved mile of concrete was in Detroit in 1909. A few years later, this is when the auto sector started to really come about with Henry Ford’s moving assembly line. Everyone tends to know about those details. But during World War II, Willow Run Airport sort of smack between Detroit and Ann Arbor, Michigan they had the biggest airplane factory in the world. They were cranking out B-24 bombers once every 63 minutes, and I’ve actually been to the office that Henry Ford and Charles Lindbergh shared. It’s still at the airport. And it was pretty cool because Henry Ford had a window built into the office that looked sort of around the corner so that he could tick off as airplanes rolled out of the hanger and make sure that they were following the same high rate production mentality that the auto sector was able to develop over the decades prior.
And so they came in to help make sure that you could leverage that industrial sector to drive very rapid production, the at-scale mentality, which is also a really important part of the notion of re-industrialization that is taking hold across the country now. Happy to get into that a bit, but yeah, Willow Run, I don’t think most folks realize that that was the biggest airplane factory in the world sitting right here in Michigan.
And all of this provided the mass production DNA that was able to help build the statewide supplier base. And today, yes, we use that for automotive, EVs, space hardware, batteries, you name it. But this is the foundation, I think, that we’ve got to be able to build on in the future. In the few decades since you saw innovations in sports, space, advanced materials, it’s like the sixties to the eighties. You said the snowboard. That was invented in Muskegon on the west side of the state in 1965.
Dow Chemical’s here in a really big way. They’ve pioneered silicone and advanced plastics in Michigan. University of Michigan’s Dr. Thomas Francis is the world’s first successful polio vaccine trials that were pioneered out of Ann Arbor, and that Big 10 research horsepower that we’ve got in the state, between the University of Michigan, Michigan State University. We also have Wayne State University in Detroit, which is a powerhouse. And then Michigan Tech University in the Upper Peninsula just recently became an R1 research institution, which essentially means those top-tier research powerhouses and that culture of tinkering matter a lot today.
I think in more recent history, you saw design and digital innovations emerge. I don’t think a lot of people appreciate that Herman Miller and Steelcase reinvented office ergonomics on the west side of the state, or that Stryker is based in Kalamazoo. They became a global medical device powerhouse over the last couple of decades, too. Michigan’s first unicorn, Duo Security, the two-factor authentication among many other things that they do there, was sold to Cisco in 2018 for 2.35 billion.
Like I said, the first unicorn in the few years since we’ve had another 10 unicorns. And I think probably what would be surprising to a lot of people is it’s in sectors well beyond mobility, it’s marketplace like StockX, FinTech, logistics, cybersecurity, of course. It’s a little bit of everything, and I think that goes to show that some of the fabric that exists within Michigan is a lot richer than what people think of, Motor City. We can scale software, we can scale life sciences innovation. It’s not just metal bending, and I talked about re-industrialization earlier. So I think about where we are today, there’s a hard tech renaissance and a broad portfolio of other high-growth sectors that Michigan’s poised to do really well in, leveraging all of that industrial base that has been around for the last century. I’m just super excited about the future and where we can take things from here.
Megan: I mean, genuinely, a really rich and diverse history of innovation that you’ve described there.
Ben: That’s right.
Megan: And last year, when Michigan’s Governor Whitmer announced this new initiative and your position, she noted the need to foster this sort of culture of innovation. And we hear that a lot that terminal in the context of company cultures. It’s interesting to hear in the context of a U.S. state’s economy. I wonder what your strategy is for building out this ecosystem, and how do you foster a state’s innovation culture?
Ben: Yeah, it’s an awesome point, and I think I mentioned earlier that I came into the role with this builder’s mentality. For me, this is how I am wired to think. This is how a lot of the companies and other founders that I spent a lot of time with, this is how they think. And so bringing this to the state government, I think of Blue Origin, Jeff Bezos’ space company, their motto, the English translation at least of it, is “Step by Step, Ferociously.” And I think about that as a lot as a proxy for how I do that within the state government. There’s a lot of iterative work that needs to happen, a lot of coaching and storytelling that happens to help folks understand how to think with that builder’s mindset. The wonderful news is that when you start having that conversation, this is one of those in these complicated political times, this is a pretty bipartisan thing, right?
The notion of how to build small businesses that create thriving main street communities while also supporting high-growth, high-tech startups that can drive prosperity for all, and population growth, while also being able to cover corporate innovation and technology transfer out of universities. All of these things touch every corner of the state.
And Michigan’s a surprisingly large and very geographically diverse state. Most of the things that we tend to be known for outside the state are in a pretty small corner of Southeast Michigan. That’s the Motor City part, but we do a lot and we have a lot of really interesting hubs for innovation and hubs for entrepreneurship, like I said, from the small mom-and-pop manufacturing shop or interest in clothing business all the way through to these insane life sciences innovations being spun out of the university. Being able to drive this culture of innovation ends up being applicable really across the board, and it just gets people really fired up when you start talking about this, fired up in a good way, which is, I think, what’s really fantastic.
There’s this notion of accelerating the talent flywheel and making sure that the state can invest in the cultivation of really rich communities and connections, and this founder culture. That stuff happens organically, generally, and when you talk about building startup ecosystems, it’s not like the state shows up and says, “Now you’re going to be more innovative and that works.” That is not the case.
And so to be able to develop those things, it’s much more about this notion of ecosystem building and getting the ingredients and puzzle pieces in the right place, applying a little bit of funding here and there, or loosening a restriction here or there, and then letting the founders do what they do best, which is build. And so this is what I think I end up being super passionate about within the state. You can lead by example in a lot of these ways, and that flywheel that I mentioned really can get going in a beautiful way when you step out of the prescriptive innovation culture mindset.
Megan: And given that role, I wonder what milestones the campaign has experienced in your first year? Could you share some highlights and some developing projects that you’re really excited about?
Ben: We had a recent one, I think that was pretty tremendous. Just a couple of months ago, Governor Whitmer signed into law a bipartisan legislation called the Michigan Innovation Fund. This was a multi-year effort that resulted in the state’s biggest investment in the innovation ecosystem development in over two decades. A lot of this funding is going to early stage venture capital firms that will be able to support the broad seeding of new companies and ideas, keep talent within the state from some of those top tier research institutions, bring in really high quality companies that early stage, growth stage companies from out of state, and then develop or supercharge some of that innovation ecosystem fabric that ties those things together. So that connective tissue that I talked about, and that was an incredible win to launch the year with.
This was just back in January, and now we’re working to get some of those funds out over the course of the next month or two so we can put them to use. What was really interesting about that was, it wasn’t just a top-down thing. This was supported from the top all the way up to and including Governor Whitmer. I mentioned bipartisan support within Michigan’s legislature and then bottom-up from all of the ecosystem partners, the founders, the investors advocating as a whole block, which I think is really powerful. Rather than trying to go for one-off things, this huge coalition of the willing got together organically and advocated for, hey, this is why this is such a great moment. This is the time to invest. And Governor Whitmer and the legislators, they heard that call, and we got something done, and so that happened relatively quickly. Like I said, biggest investment in the last two decades, and I think we’re poised to have some really great successes in the coming year as well.
Another really interesting one that I haven’t seen other states do yet, Governor Whitmer, around a year ago, signed an executive order called the Infrastructure for Innovation. Essentially, what that does is it opens up state department and agency assets to startups in the name of moving the ball forward on innovation projects. And so if you’re a startup and you need access to some very hard-to-find, very expensive, maybe like a test facility, you can use something that the state has, and all of the processes to get that done are streamlined so that you’re not beating your head against a wall. Similarly, the universities and even federal labs and corporate resources, while an executive order can’t compel those folks to do that, we’ve been finding tremendous buy-in from those stakeholders who want to volunteer access to their resources.
That does a lot of really good things, certainly for the founders, that provides them the launchpad that they need. But for those corporations and universities, and whatnot, a lot of them have these very expensive assets sitting around wildly underutilized, and they would be happy to have people come in and use them. That also gives them exposure to some of the bleeding-edge technology that a lot of these startups today are developing. I thought that was a really cool example of state government leadership using some of the tools that are available to a governor to get things moving. We’ve had a lot of early wins with startups here that have been able to leverage what that executive order was able to do for them.
Here we are talking about the MIT Technology Review to tie in an MIT piece here, we also started a Team Michigan for MIT’s REAP program. It’s the Regional Entrepreneurship Acceleration Program, and this is one of the global thought leaders on best practices for innovation ecosystem development. And so we’ve got a cohort of about a dozen key leaders from across all of those different stakeholders who need to have a seat at the table for this ecosystem development.
We go out to Cambridge twice a year for a multi-day workshop, and we get to talk about what we’ve learned as best practices, and then also learn from other cohorts from around the world on what they’ve done that is great. And then also get to hear some of the academic best practices that the MIT faculty have discovered as part of this area of expertise. And so that’s been a very interesting way for us to be able to connect outside of the state government boundaries, if you will. You sort of get out there and see where the leading edge is and then come back and be able to talk about the things that we learned from all of these other global cohorts. So always important to be focused on best practices when you’re trying to do new things, especially in government.
Megan: Sounds like there are some really fantastic initiatives going on. It sounds like a very busy first year.
Ben: It’s been a very busy first year couldn’t be more thrilled about it.
Megan: Fantastic. And in early 2023, I know that Newlab partnered with Michigan Central to establish a startup incubator too, which brought in more than a hundred startups just in its first 14 months. I wonder if you could talk a bit about how the incubator fits in with the statewide startup ecosystem and the importance of partnerships, too, for innovation.
Ben: Yeah, a key element, and I think the partnerships piece is essential here. Newlab is one of the larger components of the Southeast Michigan and especially the Detroit innovation ecosystem development. They will hit their two-year launch anniversary in just a couple of weeks, here I think. This will be mid-May, it will be two years and in that time, they’ve now got 140 plus startups all working out of their space, and Newlab they’re actually headquartered in Brooklyn, New York, but they run this big startup accelerator incubator out of Detroit as well and so this is sort of their second flagship location. They’ve been a phenomenal partner, and so speaking of the partnerships, what do those do?
They de-risk the technologies to help enable broader adoptions. Corporations can provide early revenues, the state can provide non-dilutive grant matching. Universities can bring IP and this renewable source of talent generation, and being able to stitch together all of those pieces can create some really interesting unlocks for startups to grow. But again, also this broader entrepreneurship and innovation ecosystem to really be able to thrive.
Newlab has been thrilled with their partnership in Southeast Michigan, and I think it’s a model that can be tailored across the state so that, depending on what assets are available in your backyard, you can make sure that you can best harness those for future growth.
Megan: Fantastic. What’s the long-term vision for the state’s innovation landscape when you think about it in five, 10 years from now? What do you envisage?
Ben: Amazing question. This is probably what I get most excited about. I think earlier we talked about the Willow Run B-24 bomber plant. That is what made Michigan known as the arsenal of democracy back in the day. I want Michigan to be the arsenal of innovation. We’re not trying to recreate a Silicon Valley. Silicon Valley does certain things, not trying to recreate what El Segundo wants to do in hard tech or New York City in FinTech, and all of these other things. We want to develop the thing that makes the most sense for the ingredients that Michigan can bring to bear to this challenge.
I think that becoming the Midwest arsenal of innovation, that’s something that Michigan is very well poised to use as a springboard for the decades to come. I want us to be the default launch pad for building a hard tech company, a life sciences company, an agricultural tech company. You name it. If you’ve got a design prototype and want to mass produce something, don’t want to hop coast, you want to be somewhere that has a tremendous quality of life, an affordable place, somewhere that government is at the table and willing to move fast, this is a place to do that.
That can be difficult to do in some of the more established ecosystems, especially post-covid, as a lot of them are going through really big transition periods. Michigan’s already a top 10 state for business in the next 10 years. I want us to be a top 10 state for employment, top 10 state for household median income for post-secondary education attainment, and net talent migration. Those are my four top tens that I want to see in the next 10 years. And we covered a lot of topics today, but I think those are the reasons that I am super optimistic about being able to accomplish those.
Megan: Fantastic. Well, I’m tempted to move to Michigan, so I’m sure plenty of other people will be now, too. Thank you so much, Ben. That was really fascinating.
Ben: Thanks, Megan. Really delighted to be here.
Megan: That was Ben Marchionna, chief innovation ecosystem officer at the Michigan Economic Development Corporation, whom I spoke with from Brighton, England.
That’s it for this episode of Business Lab. I’m your host, Megan Tatum. I’m a contributing editor and host for Insights, the custom publishing division of MIT Technology Review. We were founded in 1899 at the Massachusetts Institute of Technology, and you can find us in print on the web and at events each year around the world. For more information about us and the show, please check out our website at technologyreview.com.
This show is available wherever you get your podcasts, and if you enjoy this episode, we hope you’ll take a moment to rate and review us. Business Lab is a production of MIT Technology Review. This episode was produced by Giro Studios. Thanks ever so much for listening.
This content was produced by Insights, the custom content arm of MIT Technology Review. It was not written by MIT Technology Review’s editorial staff.
This content was researched, designed, and written entirely by human writers, editors, analysts, and illustrators. This includes the writing of surveys and collection of data for surveys. AI tools that may have been used were limited to secondary production processes that passed thorough human review.
Nature, Published online: 08 July 2025; doi:10.1038/d41586-025-02154-0
Expand biobank sampling to three or more generations
J Hazard Mater. 2025 Jun 23;495:139049. doi: 10.1016/j.jhazmat.2025.139049. Online ahead of print.
ABSTRACT
BACKGROUND: Chronic arsenic exposure is a global health concern linked to pulmonary diseases like fibrosis. However, its precise molecular mechanisms remain unclear. This study explored the effects of chronic arsenic exposure on a murine model (via diet) and BEAS-2B cells, focusing on oxidative stress, lipid peroxidation, mitochondrial dysfunction, and ferroptosis-mediated cell death.
METHODS: BEAS-2B cells were exposed to 1 μmol/L NaAsO₂ for 30 passages. Oxidative stress was assessed via ROS quantification, GSH depletion, and T-SOD activity. Lipid peroxidation was measured using BODIPY fluorescence and MDA levels. Mitochondrial dysfunction was determined by mtROS imaging and JC-1 staining. Ferroptosis was analyzed through GPX4 expression and TEM-based mitochondrial integrity. A 14-month murine model evaluated histopathology, metabolomic dysregulation, and gut-lung axis crosstalk.
RESULTS: Arsenic exposure significantly increased ROS, depleted GSH, and reduced T-SOD activity. Lipid peroxidation and mitochondrial dysfunction were evident, with more than 60 % decline in GPX4. Murine lung histology showed alveolar thickening, inflammatory infiltration, and elevated IL-6, TNF-α, and VEGF. Metabolomic analysis revealed disrupted lipid metabolism, correlating with ferroptosis markers (Acetyl-carnitine, L-Acetylcarnitine).
CONCLUSIONS: This was the first study to demonstrate ferroptosis as a key mechanism in arsenic-induced lung epithelial damage using a 14-month murine model and a 30-passage cellular model. We further demonstrated that ferroptosis induced by chronic exposure becomes functionally irreversible, as ferroptosis inhibition by Ferrostatin-1 failed to rescue GPX4 expression, unlike prior acute exposure models.
PMID:40614423 | DOI:10.1016/j.jhazmat.2025.139049
Ann Surg Oncol. 2025 Jul 3. doi: 10.1245/s10434-025-17738-3. Online ahead of print.
ABSTRACT
BACKGROUND: This study aimed to identify the most effective drug therapeutics for patients with the mesenchymal subtype of advanced gastric cancer (AGC). Extensive research employing diverse omics methodologies has unveiled a varied landscape of AGC. Recent progress in next-generation sequencing and other genomic technologies has facilitated a more intricate exploration of AGC at the molecular level. Nonetheless, the optimal treatment for patients with the mesenchymal subtype of gastric cancer remains elusive. Lei's molecular classification of AGC is based on gene expression profiles named "mesenchymal," "immunogenic," "classical," and "metabolic."
PATIENTS AND METHODS: Based on RNA-seq transcriptome, 234 patients were divided into four molecular subtypes: mesenchymal (n = 96), immunogenic (n = 37), metabolic (n = 61), and classic (n = 40).
RESULTS: Among those with mesenchymal-subtype AGC, compared with non-Apatinib group, the Apatinib treatment group demonstrated a significant increase in objective response rate (ORR 89.3% versus 69.3%, p = 0.038; odds ratio (OR) 0.269, 95% confidence interval (CI) (0.073-0.989)); overall survival (OS) 89.3% versus 60.2%, p = 0.010; hazard ratio (HR) 0.241, 95% CI (0.073-0.796)) and disease-free survival (DFS 78.6% versus 52.9%, p = 0.031; HR 0.400, 95% CI (0.167-0.956)). Furthermore, Apatinib significantly reduced the risk of death and recurrence in patients with mesenchymal subtype (OS: HR 0.129, 95% CI (0.030-0.563), p = 0.006; DFS: HR 0.340, 95% CI (0.138-0.833), p = 0.018). However, no significant differences were observed in the ORR, OS, or DFS between patients with metabolic and classical subtypes who underwent combination chemotherapy with additional Apatinib or camrelizumab.
CONCLUSIONS: Our analysis has revealed that, for neoadjuvant therapy in AGC, the mesenchymal subtype stands out as the ideal patient population benefiting from Apatinib.
PMID:40608168 | DOI:10.1245/s10434-025-17738-3
Nature, Published online: 02 July 2025; doi:10.1038/s41586-025-09096-7
The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.
Sci Rep. 2025 Jul 1;15(1):21173. doi: 10.1038/s41598-025-08986-0.
ABSTRACT
Effective clinical management of patients with cancer requires highly accurate diagnosis, precise therapy selection, and highly sensitive monitoring of disease burden. Caris Assure is a multifunctional blood-based assay that couples whole exome and whole transcriptome sequencing on plasma and leukocytes with advanced machine learning techniques to satisfy all three clinical testing needs on one platform. Caris Assure for therapy selection was CLIA validated using 1,910 samples. 376,197 tissue profiles along with 7,061 paired blood and tissue profiles were used to engineer features for three machine learning models. The MCED model was trained on 1,013 patients and validated on an independent set of 2,675 patients. The tissue of origin for MCED model was trained on 1,166 samples and validated using 5-fold cross validation. The MRD & Monitoring model was trained on 3,439 patients and validated on two independent sets of 86 patients for MRD and 101 patients for monitoring. For early detection, sensitivities for stages I-IV cancers (n = 284, 129, 90, 23 respectively) were 83.1%, 86.0%, 84.4%, and 95.7%, all at 99.6% specificity (n = 2149). The diagnostic first-line procedure for tissue of origin was determined for 8 categories with a top-3 accuracy of 85% for stage I and II cancers. Detection of driver mutations for therapy selection from blood collected within 30 days of matched tumor tissue, demonstrated high concordance (PPA of 93.8%, PPV of 96.8%) using CHIP subtraction. For MRD and recurrence monitoring, the disease-free survival of patients whose cancers were predicted to have an event was significantly shorter than those predicted not to have an event using a tumor naïve approach (HR = 33.4, p < 0.005, HR = 4.39, p = 0.008, respectively). The data presented here demonstrate a unified liquid biopsy platform that uses blood-based whole-exome and transcriptome sequencing coupled with artificial intelligence to address the important clinical needs in multi-cancer early detection, monitoring of MRD and recurrent cancers, and precision selection of molecularly targeted therapies.
PMID:40596693 | PMC:PMC12214926 | DOI:10.1038/s41598-025-08986-0
J Am Soc Mass Spectrom. 2025 Aug 6;36(8):1598-1608. doi: 10.1021/jasms.4c00505. Epub 2025 Jul 2.
ABSTRACT
Gastric signet ring cell carcinoma (GSRC) is an aggressive subtype of gastric cancer (GC) with a poor prognosis. The lack of a systematic molecular and metabolic heterogeneity overview has led to slow progress in clinical practice. This study used mass spectrometry imaging (MSI) to investigate the metabolic landscape of GSRC in GC tissue with various differentiation grades. Our comprehensive spatial profiling of metabolites and lipids unveiled distinct metabolic signatures across different tissue subregions. A substantial number of lipidomic biomarkers associated with GSRC were identified, including phosphatidylethanolamine N-methyl (PE-NMe), phosphatidylethanolamine (PE), sphingomyelin (SM), diacylglycerol (DG), phosphatidic acid (PA), and phosphatidylcholine (PC), which may provide insights into its pathogenesis and potential therapeutic targets. Furthermore, multi-omics network analysis revealed intricate metabolic pathways involved in GSRC progression. Our findings highlight the importance of understanding the metabolic heterogeneity of GSRC and pave the way for future studies exploring its clinical implications and therapeutic strategies.
PMID:40600435 | DOI:10.1021/jasms.4c00505
Nature, Published online: 01 July 2025; doi:10.1038/d41586-025-02016-9
The decades-old limit on how long human embryos can be grown in culture is under debate. A new road map outlines how to extend the length of culture responsibly.
Nature, Published online: 30 June 2025; doi:10.1038/d41586-025-02034-7
After a quarter of a century, the website remains an essential tool for navigating the genome and understanding its structure, function and clinical impact.
Eur J Trauma Emerg Surg. 2025 Jun 27;51(1):238. doi: 10.1007/s00068-025-02922-7.
ABSTRACT
PURPOSE: Obesity is a prevalent disease, but its influence on post-injury biology remains unclear. In this study, we aimed to characterize the independent effect of obesity on the proteomic and metabolomic signatures of trauma.
METHODS: Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center and analyzed with modern mass spectrometry-based proteomics and metabolomics. Samples obtained after start of transfusion were excluded. Patients were stratified by "obesity" (body mass index [BMI]≥30 kg/m2) vs. "no obesity" (BMI < 30 kg/m2). In sub-group analyses, patients were sub-stratified by Low Injury/Low Shock (ISS < 15, base excess [BE]≥-6mEq/L) and High Injury/High Shock (ISS≥15, BE<-6). Multiple regression was used to adjust the omics data for significant covariates prior to performing ome-wide analyses.
RESULTS: There were 183 patients included (48 [26%] with obesity and 135 [74%] without). After covariate-adjustment, multiple proteins and metabolites were correlated with ISS and/or BE and were significantly different from Low Injury/Low Shock to High Injury/High Shock only in patients with obesity. This obesity-specific omics response to injury was characterized by increased inflammation, hypercoagulability, altered nitrogen metabolism, and mitochondrial dysfunction. Patients with obesity also exhibited excessive injury-provoked tissue destruction and organ damage compared to patients without obesity. In injury severity-adjusted analyses, the obesity signature consistently displayed markers of hemolysis, likely reflecting a pre-injury hemolytic propensity.
CONCLUSION: Obesity is independently associated with altered post-injury biology, which likely underlies unique pathology in trauma patients with obesity. Identifying this aberrant response to injury is the first step in developing personalized therapies for this patient population.
PMID:40576654 | DOI:10.1007/s00068-025-02922-7
JCI Insight. 2025 Jun 26:e191595. doi: 10.1172/jci.insight.191595. Online ahead of print.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate due to late detection. PDAC arises from precursor microscopic lesions, termed pancreatic intraepithelial neoplasia (PanIN), that develop at least a decade before overt disease--this provides an opportunity to intercept PanIN-to-PDAC progression. However, immune interception strategies require full understanding of PanIN and PDAC cellular architecture. Surgical specimens containing PanIN and PDAC lesions from a unique cohort of five treatment-naïve patients with PDAC were surveyed using spatial-omics (proteomic and transcriptomic). Findings were corroborated by spatial proteomics of PanIN and PDAC from tamoxifen-inducible KPC (tiKPC) mice. We uncovered the organization of lymphoid cells into tertiary lymphoid structures (TLSs) adjacent to PanIN lesions. These TLSs lacked CD21+CD23+ B cells compared to more mature TLSs near the PDAC border. PanINs harbored mostly CD4+ T cells with fewer Tregs and exhausted T cells than PDAC. Peri-tumoral space was enriched with naïve CD4+ and central memory T cells. These observations highlight the opportunity to modulate the immune microenvironment in PanINs before immune exclusion and immunosuppression emerge during progression into PDAC.
PMID:40569674 | DOI:10.1172/jci.insight.191595
Nature, Published online: 25 June 2025; doi:10.1038/s41586-025-09202-9
Disruption of dendritic cell (DC) interstitial motility in the tumour microenvironment promotes immune evasion, and enhancement of DC interstitial motility offers a route for DC-centric immunotherapy.
Trends Mol Med. 2025 Jun 23:S1471-4914(25)00118-2. doi: 10.1016/j.molmed.2025.05.007. Online ahead of print.
ABSTRACT
Gastric cancer (GC) remains a deadly disease because of late detection and limited treatment options at advanced stages. Treatment of patients with metastatic disease is based on chemotherapy, complemented by antibodies targeting HER2, VEGFR2, and more recently PD-1 or claudin 18.2. Further targets, such as FGFR2b, as well as novel drug classes including antibody-drug conjugates (ADCs) and bispecific antibodies, are promising developments in GC treatment. Despite the failure of several targeted agents, the landscape of GC therapy is evolving rapidly, facilitated by umbrella or platform precision medicine trials. The integration of next-generation sequencing and other omics techniques into molecular tumor boards, as well as functional drug testing on patient-derived models, might bring us closer to personalized oncology and ultimately improve patient survival.
PMID:40555635 | DOI:10.1016/j.molmed.2025.05.007
Front Immunol. 2025 Jun 6;16:1606125. doi: 10.3389/fimmu.2025.1606125. eCollection 2025.
ABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is characterized by metabolic and immune heterogeneity, driving tumor progression and therapy resistance. While G protein-coupled receptors (GPCR) signaling is known to regulate metabolism and immunity in cancers, its role in LUAD remains poorly defined. This study explores the influence of GPCR signaling on LUAD metabolism and immune landscape.
METHODS: We performed non-negative matrix factorization (NMF) clustering of GPCR signaling genes in TCGA-LUAD cohort to identify distinct molecular subgroups. A prognostic model was developed based on GPCR signaling genes using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression. Differentially expressed genes were analyzed for metabolic pathway enrichment and immune infiltration. In addition, key genes within GPCR signaling were identified and validated through functional assays.
RESULTS: NMF clustering based on GPCR signaling identified three subgroups in LUAD, with cluster 3 exhibiting poorer overall survival and significant enrichment in multiple prognostic associated metabolism pathways including purine, pyrimidine, glyoxylate and dicarboxylate metabolism. Then, we developed a GPCRscore prognostic model and validated across multiple cohorts, which effectively stratified LUAD patients into distinct risk groups. High-risk LUAD patients had an immunosuppressive microenvironment and activated metabolic reprogramming. ADM was identified as a key gene in the high-risk group, correlating with tumor stage, immune suppression, and resistance to immunotherapy. Clinically, ADM was highly expressed in tumor tissues and shows elevated concentrations in the peripheral blood of patients with advanced-stage LUAD. Subsequently, we demonstrated that knock-down of ADM in LUAD cells impaired their proliferation, migration, and invasion, while also reducing the angiogenic potential of endothelial cells in vitro. Adrenomedullin promoted LUAD progression in a murine metastasis model. Further, adrenomedullin inhibited CD8+ T cells proliferation, induced exhaustion, and impaired cytotoxic function. Finally, drug sensitivity and cell viability analysis showed LUAD patients with high levels of ADM exhibited sensitivity to the treatment of Staurosporine and Dasatinib.
CONCLUSIONS: In summary, this study reveals the pivotal role of GPCR signaling particularly mediated by ADM in orchestrating metabolic reprogramming and immune modulation in LUAD. ADM emerges as a potential predictive biomarker and therapeutic target, offering valuable implications for optimizing strategies.
PMID:40547013 | PMC:PMC12179119 | DOI:10.3389/fimmu.2025.1606125
When testing an AI model, it’s hard to tell if it is reasoning or just regurgitating answers from its training data. Xbench, a new benchmark developed by the Chinese venture capital firm HSG, or HongShan Capital Group, might help to sidestep that issue. That’s thanks to the way it evaluates models not only on the ability to pass arbitrary tests, like most other benchmarks, but also on the ability to execute real-world tasks, which is more unusual. It will be updated on a regular basis to try to keep it evergreen.
This week the company is making part of its question set open-source and letting anyone use for free. The team has also released a leaderboard comparing how mainstream AI models stack up when tested on Xbench. (ChatGPT o3 ranked first across all categories, though ByteDance’s Doubao, Gemini 2.5 Pro, and Grok all still did pretty well, as did Claude Sonnet.)
Development of the benchmark at HongShan began in 2022, following ChatGPT’s breakout success, as an internal tool for assessing which models are worth investing in. Since then, led by partner Gong Yuan, the team has steadily expanded the system, bringing in outside researchers and professionals to help refine it. As the project grew more sophisticated, they decided to release it to the public.
Xbench approached the problem with two different systems. One is similar to traditional benchmarking: an academic test that gauges a model’s aptitude on various subjects. The other is more like a technical interview round for a job, assessing how much real-world economic value a model might deliver.
Xbench’s methods for assessing raw intelligence currently include two components: Xbench-ScienceQA and Xbench-DeepResearch. ScienceQA isn’t a radical departure from existing postgraduate-level STEM benchmarks like GPQA and SuperGPQA. It includes questions spanning fields from biochemistry to orbital mechanics, drafted by graduate students and double-checked by professors. Scoring rewards not only the right answer but also the reasoning chain that leads to it.
DeepResearch, by contrast, focuses on a model’s ability to navigate the Chinese-language web. Ten subject-matter experts created 100 questions in music, history, finance, and literature—questions that can’t just be googled but require significant research to answer. Scoring favors breadth of sources, factual consistency, and a model’s willingness to admit when there isn’t enough data. A question in the publicized collection is “How many Chinese cities in the three northwestern provinces border a foreign country?” (It’s 12, and only 33% of models tested got it right, if you are wondering.)
On the company’s website, the researchers said they want to add more dimensions to the test—for example, aspects like how creative a model is in its problem solving, how collaborative it is when working with other models, and how reliable it is.
The team has committed to updating the test questions once a quarter and to maintain a half-public, half-private data set.
To assess models’ real-world readiness, the team worked with experts to develop tasks modeled on actual workflows, initially in recruitment and marketing. For example, one task asks a model to source five qualified battery engineer candidates and justify each pick. Another asks it to match advertisers with appropriate short-video creators from a pool of over 800 influencers.
The website also teases upcoming categories, including finance, legal, accounting, and design. The question sets for these categories have not yet been open-sourced.
ChatGPT-o3 again ranks first in both of the current professional categories. For recruiting, Perplexity Search and Claude 3.5 Sonnet take second and third place, respectively. For marketing, Claude, Grok, and Gemini all perform well.
“It is really difficult for benchmarks to include things that are so hard to quantify,” says Zihan Zheng, the lead researcher on a new benchmark called LiveCodeBench Pro and a student at NYU. “But Xbench represents a promising start.”
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