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MiniMax Releases M1: a 456B Hybrid-Attention Model for Long-Context Reasoning and Software Tasks

MiniMax has introduced MiniMax-M1, a new open-weight reasoning model built to handle extended contexts and complex problem-solving with high efficiency. Built on top of the earlier MiniMax-Text-01, M1 features a hybrid Mixture-of-Experts (MoE) architecture and a novel “lightning attention” mechanism.

By Robert Krzaczyński
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Gastric cancer: from biomarkers to functional precision medicine

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

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Integrative Multi-Omic and Immune Profiling of Lung Adenocarcinoma: Molecular Landscapes, Gene Expression, and Treatment Response Insights

Oncologist. 2025 Jun 24:oyaf191. doi: 10.1093/oncolo/oyaf191. Online ahead of print.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is a major cause of cancer death. Traditional histopathological classification overlooks molecular heterogeneity, limiting personalized treatment. This study used multiomic data to define LUAD subtypes, assess prognostic significance, and analyze immune features, aiming to improve targeted therapy and clinical outcomes.

METHODS: This study used Consensus Clustering and Gap Statistics to analyze LUAD multiomic data, including mRNA, lncRNA, miRNA, DNA methylation, and mutations. Clustering was validated by silhouette plots and heatmaps. Molecular characterization involved regulon activity, immune and metabolic profiling. Functional assays (qPCR, WB, CCK-8, flow cytometry) assessed NDNF's role in LUAD.

RESULTS: Two molecular LUAD subtypes showed distinct clustering and survival outcomes. One subtype had worse prognosis and unique immune features, including checkpoint expression and microenvironment differences. Gene signatures and metabolism varied by subtype. NDNF was downregulated in tumors; its overexpression suppressed LUAD cell viability and promoted apoptosis, suggesting tumor-suppressive function.

CONCLUSION: This study identifies two LUAD subtypes with distinct molecular and immune features linked to prognosis and therapy response. NDNF downregulation and its tumor-suppressive effects highlight its therapeutic potential. These findings support improved LUAD stratification and personalized treatment strategies.

IMPLICATIONS FOR PRACTICE: This study reveals two LUAD molecular subtypes with distinct prognoses and immune features, offering a basis for more precise treatment strategies. The identification of NDNF as a potential tumor suppressor suggests its value as both a biomarker and therapeutic target. These findings support improved LUAD stratification and personalized therapy.

PMID:40554675 | DOI:10.1093/oncolo/oyaf191

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Unraveling the role of GPCR signaling in metabolic reprogramming and immune microenvironment of lung adenocarcinoma: a multi-omics study with experimental validation

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

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More news from the labs of MIT


Hundred-year storm tides could strike every decade in Bangladesh

Tropical cyclones can generate devastating storm tides—seawater heightened by the tides that causes catastrophic floods in coastal regions. An MIT study finds that as the planet warms, the recurrence of destructive storm tides will increase tenfold for one of the world’s hardest-hit regions.

New electronic “skin” could lead to lightweight night-vision glasses 

MIT engineers have developed a technique to grow and peel ultrathin “skins” of electronic material that could be used in wearable sensors, flexible transistors and computing elements, and sensitive compact imaging devices.

Technology makes pesticides stick to plant leaves

A new pesticide application system developed by MIT researchers and their spinoff company could significantly cut use of pesticides and fertilizers, saving farmers money and reducing polluting runoff.

New printable metamaterials that are both strong and stretchy could allow fabrication of bendable ceramics, glass, and metals.

These tough yet bendy materials could be made into tear-resistant textiles, flexible semiconductors, electronic chip packaging, and durable yet compliant scaffolds on which to grow cells for tissue repair.

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Cancer-targeting nanoparticles are moving closer to human trials

Over the past decade, Institute Professor Paula Hammond ’84, PhD ’93, and her students have used a technique known as layer-by-layer assembly to create a variety of polymer-coated nanoparticles that can be loaded with cancer-fighting drugs. The particles, which could prevent many side effects of chemotherapy by targeting tumors directly, have proved effective in mouse studies. Now the researchers have come up with a technique that allows them to manufacture many more particles in much less time, moving them closer to human use.

“There’s a lot of promise with the nanoparticle systems we’ve been developing, and we’ve been really excited more recently with the successes that we’ve been seeing in animal models for our treatments for ovarian cancer in particular,” says Hammond, the senior author of a paper on the new technique along with Darrell Irvine, a professor at the Scripps Research Institute.

In the original production technique, layers with different properties can be laid down by alternately exposing a particle to positively and negatively charged polymers, with extensive purification to remove excess polymer after each application. Each layer can carry therapeutics as well as molecules that help the particles find and enter cancer cells. But the process is time-consuming and would be difficult to scale up. 

In the new work, the researchers used a microfluidic mixing device that allows them to sequentially add layers as the particles flow through a microchannel. For each layer, they can calculate exactly how much polymer is needed, which eliminates the slow and costly purification step and saves significantly on material costs.

gloved hands hold the device
This microfluidic device can be used to assemble the drug delivery nanoparticles rapidly and in large quantities.
GRETCHEN ERTL

This strategy also facilitates compliance with the FDA’s GMP (good manufacturing practice) requirements, which ensure that products meet safety standards and can be manufactured consistently. “There’s much less chance of any sort of operator mistake or mishaps,” says Ivan Pires, PhD ’24, a postdoc at Brigham and Women’s Hospital and a visiting scientist at the Koch Institute, who is the paper’s lead author along with Ezra Gordon ’24. “We can create an innovation within the layer-by-layer nanoparticles and quickly produce it in a manner that we could go into clinical trials with.”

In minutes, the researchers can generate 15 milligrams of nanoparticles (enough for about 50 doses for certain cargos), which would have taken close to an hour with the original process. They say this means it would be realistic to produce more than enough for clinical trials and patient use.

To demonstrate the technique, the researchers created layered nanoparticles loaded with the immune molecule ­interleukin-­12; they have previously shown that such particles can slow growth of ovarian tumors in mice. Those manufactured using the new technique performed similarly to the originals and managed to bind to cancer tissue without entering the cancer cells. This lets them serve as markers that activate the immune system in the tumor, which can delay tumor growth and even lead to cures in mouse models of ovarian cancer. 

The researchers have filed for a patent and are working with MIT’s Deshpande Center for Technological Innovation in hopes of forming a company to commercialize the technology, which they say could also be applied to glioblastoma and other types of cancer. 

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