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Mutations in the follicle-stimulating hormone receptor (FSHR) cause spontaneous ovarian hyperstimulation syndrome (OHSS). Here, the authors report that estrildid finches naturally carry an analogous pathogenic mutation found in patients but avoid the syndrome by lowering a related receptor’s activity. Blocking this receptor successfully treats OHSS in mice.

Most kiwifruit species are vulnerable to high levels of heat stress. Here, the authors report natural variation at the GATA transcription factor binding site of EGY3 gene mediates chloroplastic ROS homeostasis to confer kiwifruit thermotolerance.

Osteoarthritis is driven by epigenetic dysregulation, yet targeted therapies remain elusive. Here, the authors develop a cartilage-targeting hydrogel delivering BRD4-degrading PROTACs to suppress the BRD4- Nav1.7 axis and alleviate osteoarthritis.

In this study, the authors identify an Aurka–Bhlhe41 axis, which prevents microglia from aging-like dysfunction by limiting CD22 upregulation, preserving myelin debris clearance and remyelination, and highlighting a potential therapy target for neurodegeneration.

Grain chalkiness is an undesirable trait that severely compromises rice quality. Here, the authors report the cloning of an E3 ubiquitin ligase encoding gene Chalk9 and reveal its crucial role in regulating grain chalkiness through mediating the ubiquitination-dependent degradation of OsEBP89.

Determining the optimal start of the growing season presents a fundamental dilemma for plants. This meta-analysis suggests that plants exhibit high freezing resistance (to -12 °C) and low lethal frost risk (safety margin of 17 °C) during spring emergence, indicating strong long-term evolutionary pressure.

The cellular pathology of Japanese encephalitis (JE) remains elusive. Here, the authors use spatial transcriptomics in JE mouse model and show that Ackr1⁺ endothelial cells and Ly6c2⁺ monocytes synergistically drive neuroinflammation, revealing potential therapeutic targets for neurotropic virus infections.

Using pear as a study system, the biosynthetic pathway of acetophenones has been elucidated: naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs leads them to undergo hydrolysis, followed by decarboxylation, to yield acetophenones.

Neutrophils are known to be important in COPD pathogenesis and calcium signaling is involved in this process. Here the authors examine the function of Na⁺Ca²⁺ exchanger 1 (NCX1) in neutrophil function in mouse models of chronic cigarette smoke exposure and show that inhibition of NCX1 reduces neutrophil accumulation in the lungs and formation of neutrophil extracellular traps (NETs).

Lisinopril is identified as a BI1 activator that counteracts ALS pathology. It remodels lipid metabolism, restores autophagic flux via TGFβ1/mTOR signaling, and mitigates fibrosis. This multi-target mechanism supports the therapeutic repurposing of lisinopril for ALS.

Grain protein content determines rice nutrition quality. Here, the authors show that a single nucleotide polymorphism in the promoter region of OsGluA2, encoding a glutelin type-A2 precursor, is responsible for glutelin content difference between the indica and japonica rice subspecies.

Tunnel oxide passivating contact solar cells face unresolved questions about the atomic scale nature of pinholes that limit performance. The authors use aberration corrected transmission electron microscopy to reveal two pinhole types and showing that oxygen-based passivation rather than pinholes geometry drives efficiency.

Deep skin injuries often lead to scarring. Here, the authors show that restoring GAS6 via an mRNA-hydrogel platform enhances wound healing and reduces fibrosis in preclinical models.

cf-EpiTracing enables automated profiling of histone modifications in cell-free DNA from human plasma, allowing identification of the cells of origin and disease diagnosis.

Disentangling intertwined orders in quantum materials is challenging. Now, photoemission spectroscopy experiments show that magnetic fields can be used to disentangle such orders in a kagome superconductor.

The propagation of structured light in free space is bound to the existing solutions of Helmholtz equation. Here, authors propose a hydrodynamic formulation of optics to design and generate well-known beam families and introduce additional specialized modes. The formalism is experimentally validated through optical tweezers and free-space communications.

An injectable pH-sensitive nanoadjuvant is shown to induce effective pyroptosis of tumours, which, combined with the in situ photoactivable release of TLR agonists, generates a strong vaccine-like response to eradicate the tumour.

Thiamine pyrophosphate (TPP) is the biologically active form of vitamin B1 and servers as an essential metabolic cofactor regulating energy production, redox homeostasis, and carbon assimilation. Here, the authors show that optimizing TPP metabolism can enhance yield and quality in maize, rice and rapeseed.

Enzymes often function in crowded environments due to the high concentration of macromolecules and the formation of biomolecular condensates, but most insights into enzyme kinetics stem from dilute solution studies. Here, the authors present a residue-resolved dynamic energy landscape model that explicitly accounts for the crowding agent, reporting a crowding-induced allosteric regulation mechanism of enzymatic catalysis for a model enzyme, adenylate kinase, and providing a computational framework for understanding the diversity of existing experimental observations.

A flexible digital artificial intelligence chip with a compute-in-memory architecture is fabricated using a commercial low-temperature polycrystalline silicon thin-film transistor process and shows high accuracy in human daily activity monitoring using multimodal physiological signals.

A short peptide derived from a commensal-fungal-secreted protein promotes repair in models of colon epithelial damage when delivered directly or via probiotic microbes.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

Molecular mechanisms determining soybean seed weights remain largely elusive. Here, the authors identify a 14-3-3 protein encoding gene GmSMS6 negatively regulates soybean seed weight and size via the possible interactions with the transcription factor GmbZIP151 and the RING-type E3 ligase GmUBQ1.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The authors show that NAT10 is upregulated with T cell antigen receptor signaling and that T cell-specific NAT10 deficiency results in diminished numbers of naive T cells, translating to an inability to mount a significant antiviral T cell response.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

Runoff contributes almost equally to stream temperature as air temperature in a Qinghai-Tibetan watershed, and under high-emission scenarios the influence of groundwater is projected to increase, leading to spring and winter warming, according to hydrological–thermal modeling

In this study, authors reveal an evolutionary strategy in bacteria, where multidrug resistance are stably maintained through multicopy heterogeneous genes on a single plasmid, conferring an adaptive advantage under fluctuating clinical drug pressures.

Elucidation of drought tolerance mechanism would help to develop tolerant crops. Here, the authors reveal the interaction between BBX18, a zinc finger transcription factor, and ascorbate peroxidase (APX1) to mediate drought stress resistance in tomato.

Thymine DNA glycosylase (TDG) was identified as a synthetic-lethal target in p53-deficient cancers through alterations in double-stranded RNA accumulation. A covalent small-molecule inhibitor of TDG exhibited potent efficacy against p53-deficient tumors.

Selective functionalization of polyfluoroalkyl compounds is vital for advancing pharmaceuticals, agrochemicals, and high-performance materials but is hindered by the stability of C(sp³)–F bonds. Here, the authors report a dual photoredox/cobalt catalytic strategy enabling redox-driven defluoroallylation of perfluoroalkylarenes and polyfluorinated aliphatic amides.

Macrocyclization typically proceeds via thioesterase mediation in type I polyketide synthases. Now, using genome mining and crystallographic analysis, an alternative mechanism for stereoselective macrocyclization in the akaeolide biosynthetic pathway is reported. The mechanism is proposed to proceed via an iminium-catalysed tandem Michael addition and Knoevenagel condensation, using nuclear transport factor 2-like enzymes.

Using volatile vanadium oxide and non-volatile tantalum oxide/hafnium oxide memristor arrays, a first-principles Fourier transform system can be created that can outperform conventional Fourier transform hardware in terms of throughput and reduce memory cost.

The key regulators driving intrinsic immune responses and neuropathic pain remain elusive. Here, the authors elucidate that ZFP612-mediated epigenetic disinhibition of Il1rl1 within the 3D genome in dorsal root ganglion neurons causes neuropathic pain.

The spatial organisation of the tumour microenvironment (TME) can affect immune responses that control tumour growth. Here, the authors use single-cell transcriptomics and spatial transcriptomics to identify a lymphocyte aggregated region (LAR) in gastric cancer and compare its cellular and molecular composition with the neighbouring TME.

Butenolides are important features of many bioactive compounds but known butenolide biosynthetic pathways are complex and challenging to harness. In this study, the authors report that avenolide, a 4-alkylbutenolide that regulates avermectin production in Streptomyces avermitilis, is assembled from a fatty acyl thioester by a multifunctional flavoenzyme and an iterative cytochrome P450.

The detailed mechanism of how hypoxia and acidity promote immune exclusion remains unclear. The authors here identify that GPR4, a proton sensor, induces immune exclusion by facilitating collagen alignment via upregulating LOXL2. Furthermore, inhibiting LOXL2 or GPR4 signal pathway alleviates immune exclusion.

This study leverages plasma proteomics from over 50,000 individuals to build organ-specific aging models and uncover underlying genetic mechanisms. It also investigates causal links between organ aging, diseases, and lifestyle, providing insights for promoting healthy longevity.