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Tumor endothelial cells are essential stromal components in the tumor microenvironment. Here the authors find that endothelial-specific deletion of PDLIM5, an actin-binding protein, could inhibit tumor angiogenesis and tumor growth as well as enhance therapeutic responses in mouse tumor models.

Klebsiella pneumoniae clonal group 23 is a public health concern due to hypervirulence and carbapenem resistance. Here, the authors sequence 13 new isolates of the ST218-KL57 strain from China and conduct genomic analyses to investigate evolutionary divergence and resistance patterns.

In this work, Wu et al. develop and present PolyCLOVER, a framework that integrates multi-stage learning, active learning, and high-throughput experimentation to iteratively discover potent, low-toxicity polymeric antibiotics without relying on external labelled data.

Subtle variation can reshape protein structure but are hard to identify. Here, authors present MELO, which measures and locates structural changes, outperforms existing tools, and uncovers over 10,000 previously missed protein structure change pairs.

Multimodal brain recordings are no easy task. Here, the authors introduce a neural implant with integrated carbon nanotube field-effect transistors for multimodal recording of electrical and chemical signals.

Medullary thyroid carcinoma (MTC) is a rare and aggressive neuroendocrine tumor with limited risk stratification. Here, the authors perform multi-omic analysis of MTC samples from 452 patients across 10 Chinese clinical centers, identify molecular subtypes and develop a prediction model.

A mechano-intelligent transmission mechanism based on the slipknot delivers precise force signals for clinical practice and robotic operations such as minimally invasive surgery and tendon-driven robotics.

In this work, authors present their goal-directed subgroup identification (GD-SI) framework, reconciling biological heterogeneity with clinical actionability, and offering a scalable infrastructure for precision trial design and personalized sepsis management.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.

Active lifestyle has considerable cardiac health benefits, but the metabolic and immunological background need further investigation. Here the authors show that a cardiac macrophage population, characterised by simultaneous pro-inflammatory and reparative properties, accumulate upon exercise, and these cells restore cardiac health upon transfer in a mouse model of sepsis-induced cardiomyopathy.

This study demonstrates that ABHD10, a mitochondrial depalmitoylase, is indispensable for male fertility in mice. ABHD10 deficiency causes sperm motility defects by disrupting mitochondrial sheath formation and oxidative phosphorylation.

Antimicrobial resistance poses a significant global health threat, necessitating swift and precise diagnostic solutions. Here, the authors introduce a culture-free diagnostic platform integrating microfluidic cell enrichment, single-cell Raman spectroscopy, and deep learning, that identifies bacterial and fungal infections directly from clinical samples within 20 minutes.

TMAO from gut microbes has been linked to some cases of atherosclerosis. Here, authors report on the use of nano-functionalized probiotics to reduce the production and absorption of TMA, reduce plasma TMAO levels, and alleviate the progression of atherosclerotic plaques.

Neuropathic pain is driven by chronic neuroinflammation involving dysfunction of microglia and astrocytes. Here, the authors develop nanoparticles that block TDP-43 aggregation and suppress glial activation via the cGAS-STING pathway in a mouse model, highlighting a promising therapeutic strategy.

Circadian rhythms shape epidermal stem cell fate by regulating rhythmic gene expression in human EPSCs. ZFP42 maintains stemness by sustaining CRY1 expression, promoting proliferation and restraining differentiation to preserve epidermal homeostasis.

The authors conducted a genome-wide association study of bipolar disorder (BD) in Han Chinese and integrated PGC4 East Asian and European datasets, discovering 23 novel loci, prioritizing 39 credible risk genes and implicating BD-related cell types and druggable targets.

Pla2g7 is a secreted enzyme mainly produced by myeloid cells and exerts a significant role in a spectrum of metabolic and inflammatory disorders. Here they show that Pla2g7 expression is enriched in osteoclasts and is associated with bone resorption, revealing an important role in bone homeostasis.

Growth factor signalling has been shown to alleviate tissue fibrosis and promote repair. Here, the authors use fibroblast growth factor 7 (FGF7) knockout mice and an FGF7-loaded hydrogel to show that this factor can promote functional regeneration of tendon.

He, Teng and Yang et al. report how metformin, the widely used antidiabetic drug, inhibit its target, the respiratory complex I, through a distinct state-dependent, inhibitor trapping mechanism, thus providing the molecular basis for its superior clinical tolerance.

Previous clinical studies suggested that Insulin-like growth factor binding-protein 7 (IGFBP7) is elevated in early stages of diabetes. Here authors showed tubule and glomerular-specific IGFBP7 promotes diabetic kidney disease.

A spatiotemporally adaptive targeting strategy ensures sequentially reprogramming metabolism of inflammatory macrophages and senescent stem cells via intracellular NAD⁺ replenishment, accelerating bone and skin tissue regeneration.

Wang, He, Gong and colleagues identify an age-related decline in the palmitoyltransferase ZDHHC11 in chondrocytes that leads to senescence and the pathogenesis of osteoarthritis, highlighting the potential of targeted ZDHHC11 delivery as a therapeutic strategy for osteoarthritis.

A tunable magnetic nanochains platform (EVGpro) enables tandem enrichment, proteomic, and N-glycoproteomic analysis of extracellular vesicles from ultratrace biofluids. EVGpro identifies N-glycoprotein signatures and two asthenozoospermia subtypes.

Flat bands are interesting as their high density of states and suppressed kinetic energy result in strongly enhanced electronic correlations, leading to emergent and unconventional ordered states. Here, the authors use photoelectron momentum microscopy to map an isolated flat band in NbOCl₂ across the entire Brillouin zone, revealing its tunable quasiparticle band gap and offering a platform for flat-band physics exploration.

Efforts to develop P2X7 drugs are hampered by species differences. Here, authors reveal the structural basis for these disparities and show that transgenic mice provide a powerful model for testing selective inhibitors with greater clinical relevance.

The roles of liver-specific genes in hepatocellular carcinoma (HCC) remain to be explored. Here the authors report that PGRMC1, localized to the endoplasmic reticulum (ER) membrane, functions as a tumor suppressor in HCC by inhibiting c-Myc protein translation via activation of PERK independent of ER stress.

ANPELA is a software package to compare and assess the performance of different workflows for processing single-cell proteomic data, ensuring the user selects the most appropriate processing workflow for their experimental design question.

ALKBH8 is a tRNA methyltransferase, specifically modifying the wobble uridine (U34) in tRNAs. Here, the authors discover that ALKBH8 is a direct transcriptional target of β-catenin, and that mediates intestinal tumorigenesis through regulation of the translation of KRAS in a codon-dependent manner.

Viruses such as EBV use various mechanisms to avoid antiviral responses. Here the authors propose that the EBV protein BRRF2 is secreted via extracellular vesicles from NPC cells, disrupts the cGAS-STING pathway, reduces cGAS-DNA phase separation and the subsequent antiviral response.

In a phase 1 trial, the co-infusion of CD19-targeting and BCMA-targeting CAR-T cells in adults with treatment-refractory lupus was safe and had promising efficacy, with most patients achieving remission after 3 months.

In a prespecified interim analysis of the randomized, double-blind phase 3 COMPASSION-15 trial, patients with advanced HER2-negative gastric/GEJ cancer treated with the anti-PD-L1/CTLA-4 bispecific Ab cadonilimab plus chemotherapy showed significantly improved overall survival compared with patients treated with placebo plus chemotherapy as first-line treatment.

RNA velocity offers insight into cell dynamics but faces key limitations across modalities. Here, authors present GraphVelo, a machine learning framework that refines and extends RNA velocity to multimodal data, enabling quantitative, interpretable cell state transitions.

Here, the authors show that Msx2 deficiency prevents osteoclast fusion and enhances type H vessel- mediated osteogenesis. Mechanically, MSX2 protects PU.1 from FBXW7 mediated degradation and targeting Msx2 serves as an anabolic therapy in pre-clinical models of osteoporosis.

Wang, Wang, Pan and colleagues uncover a C864–C869 disulfide linkage stimulated by viral RNA that drives RIG-I activation, phase separation and stimulates downstream innate immune signalling.

Artificial cilia array devices are developed for sound frequency decoding and executing tasks such as drug release.

By resonant excitation of an InAs quantum dot embedded in a microcavity, a deterministic single-photon source is demonstrated. Single-photon purity of 0.9795(6), photon indistinguishability of 0.9856(13), and an overall end-to-end efficiency of 0.712(18) are simultaneously obtained.

Fluid management in septic shock lacks personalized approaches, which are critical for improving patient outcomes. Here, the authors show that a proteomic signature can help identify patients who may benefit from a restrictive fluid strategy, potentially reducing hospital mortality rates.