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Papaya is a trioecious species with XX females, XY males, and XY^h hermaphrodites, and the combination of Y and Y^h chromosomes is lethal. Here, the authors identify the degeneration of the YY lethality gene on the Y chromosome as the causal balancing lethal factor that reenforces dioecy and stabilizes balanced sex ratios.

The performance of π-conjugated polymers films is limited by the short exciton diffusion lengths due to local imperfections or variations in interchain packing. Here, the authors report on large-area submillimeter-scale spherulites achieved by treating a spin-coated polydiarylfluorene film under solvent vapor annealing.

This work identifies ERECTA–EPFL genes as major regulators of maize meristem activity and the development of maize shoots and ears. The findings highlight genetic targets that influence kernel row number and plant architecture to increase maize yield.

Climate limits where insects can live and which species can coexist. Using thermal tolerances of 653 moths on Asian mountains, this study shows warmer temperatures broaden thermal tolerance traits diversity; daily variation has little influence, and strong seasonality mildly weakens this pattern.

Insufficient efficacy is one of the major impediments for further application of sup-tRNA therapies. Here, authors engineer the body sequence of sup-tRNA^Arg and restored retinal function and vision-guided behavior in a mouse model carrying the RPE65-R44X nonsense mutation.

By analyzing the structures of the Polycomb repressive deubiquitinase complex, which catalyzes the deubiquitination of H2AK119Ub on nucleosomes, Zhang, Zheng, Tong and Deng et al. reveal that ubiquitin acts as a proteinaceous glue to fasten the intersubunit interaction within the complex to allosterically enhance its activity.

Liquid crystals on silicon (LCoS) devices are limited by the polarization sensitivity and reliance on complex architectures for full-color integration. Here, the authors demonstrate a metasurface-integrated LCoS device for polarisation-insensitive, full-color amplitude modulation on a single chip.

Histone H2B S112 O-GlcNAcylation facilitates H2B K120 monoubiquitylation, which promotes transcriptional activation; however, the mechanism is unknown. Structural and biochemical characterization reveals that the O-GlcNAc moiety has a unique role by allosterically activating the E2 enzyme RAD6A and directly enhancing its enzymatic activity.

Biomimetic artificial nanochannels have potential applications in signal regulation and subcellular biosensing. Here authors present artificial nanochannels based on DNA-functionalized glass nanopipettes, which when targeted to mitochondria can be used to evaluate and manipulate the interaction network between mitochondria and other organelles.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Using generative AI, Insilico Medicine developed an oral PROTAC that potently inhibits and degrades PKMYT1, a synthetically lethal target in cancer, demonstrating high selectivity and strong antitumor efficacy in preclinical models.

Here authors show loss of AKAP11, a strong genetic risk factor for bipolar disorder and schizophrenia, disrupts PKA proteostasis and signaling, leading to widespread transcriptomic alterations across the brain, particularly in striatal neurons, as well as altered behavior.

This study reveals how Tau pathology in spinal neurons contributes to early tactile deficits in Alzheimer’s disease, linking sensory dysfunction to cognitive decline. It highlights potential peripheral biomarkers and new therapeutic targets beyond the brain.

Antibacterial compounds are discovered by combining phenotypic screening with deep learning.

Elebsiran plus PEG-IFNα improved hepatitis B surface antigen (HBsAg) loss rates compared with PEG-IFNα alone in patients with chronic hepatitis B virus infection. Furthermore, prior response to the BRII-179 vaccine was associated with higher HBsAg clearance, suggesting its potential as a predictive tool for identifying patients more likely to benefit from therapies.

Bi, Mo, Liu et al. carry out high-throughput screening and analysis to profile genome-wide pro-tumour enhancers and uncover enhancer connectomes in glioma. In particular, they identify specific single-nucleotide polymorphisms associated with glioma risk and progression.

A screen for protein degraders discovers hits by imaging cell survival.

This study identifies a regulatory module in which UBC32 and SC35 regulate bZIP49 splicing to maintain potassium balance, revealing how poplar adapts to salt stress and providing new insights into plant responses to soil salinity.

Limitations in proton transport within electrode materials diminish the proton storage capacity in aqueous zinc-organic batteries. Here, authors report an organic small molecule composite electrode enabling superharmonic fast proton motion via a crosslinked short hydrogen bond network, resulting in an electrode energy density up to 400 Wh kg⁻¹.

Wnt-activated distal blastema cells, which are largely non-proliferative, act as organizing center to regulate the proliferation and migration of blastema cells via modulating FGF20 and FGFR4 expression during tail regeneration of Gekko japonicus.

The apelin receptor regulates heart and metabolic health via G-protein and β-arrestin signaling pathways. Here, authors present receptor-β-arrestin complex structures with distinct stoichiometries that provide insight into biased signaling, guiding targeted drug design.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Previous ophthalmic foundation models have struggled to generalize effectively to diverse and rare fundus diseases, restricting their clinical applicability. Here, the authors introduce a vision-language foundation model that demonstrates superior performance in diagnosing both common and rare fundus conditions.

Epstein–Barr virus - host chromatin interactions in nasopharyngeal carcinoma remain poorly understood. Here, the authors characterise the virus‒host chromatin interactions leading to genome reorganisation and identify a KDM5B-relevant signature associated with distant metastasis.

Toxic methylmercury in soil can accumulate in rice grains. Here, the authors use DNA stable-isotope probing and metagenomics to identify soil microbes and pathways potentially involved in methylmercury degradation.

The understanding of kagome bands, which are characterized by Dirac-like bands capped by a flat band, remains largely elusive. Here, Liu et al. report the observation of a flat band and Dirac bands as ideal features of kagome bands in CoSn, revealing orbital-selective character.

Cross-dehydrogenative coupling (CDC) of C-H bonds is an ideal approach for C-C bond construction but suffers from low selectivity of similar C-H bonds. Here, the authors describe a highly selective paired electrocatalysis strategy towards CDC combining hydrogen evolution reaction catalysis with hydride transfer catalysis.

The apelin receptor (APJR) is a drug target for cardiovascular and metabolic health. Here, authors reveal how ligand binding, receptor dimerization, and G protein coupling cooperate to regulate APJR signaling pathway, providing insight for drug discovery.

The K29/K48 hetero-polyubiquitin signal has been reported to be an enhanced degradation signal, but the enzymatic mechanism of this ubiquitin chain formation is unclear. Here, the authors reveal how the HECT E3 ligase Ufd4/TRIP12 generates K29/K48 branched ubiquitin chains and provide structural insights into this process.

The genomic epidemiology of Acinetobacter baumannii, which is rising in virulence and multidrug resistance, was explored. This study examined bloodstream infection isolates from Chinese patients in 2011–2021, revealing increased genetic diversity and dominance of highly virulent ST208.

Zhao et al. report a smart phosphor that exhibits adaptive light-induced photoluminescence variation and dark recovery with non-destructive readout functions. It mimics synaptic behaviors in a full-photoluminescent manner, enabling an alternative way of all-optical physical reservoir computing.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Nie et al. show that myocardial CCDC25 detects doxorubicin-induced neutrophil extracellular trap DNA and activates reactive oxygen species production and autophagy, leading to cardiotoxicity. Targeting CCDC25 exerts a cardioprotective effect without impacting the antitumor activity of doxorubicin in lymphoma and breast cancer models.

Chiral α-tertiary amines and tertiary alcohols are prevalent in bioactive molecules yet challenging targets to access. Here, the authors provide a dinuclear zinc-catalyzed desymmetric approach based on readily available malonic esters.

Through rational engineering of A3A deaminase, Yang and colleagues have designed CBEs termed haA3A-CBEs, which feature a condensed editing window and minimal off-target effects that are independent of defined sequence contexts and methylation status.

In a prospective study including 2,300 pediatric and adult patients with liquid and solid tumors, RNA sequencing provided actionable molecular information in 87% of cases, with applications in diagnostics and therapy matching.

Cobalt-free Mn-based lithium metal batteries suffer from serious Mn dissolution and lithium dendrite problems. Here, authors propose ferrocene hexafluorophosphate as an electrolyte additive to achieve dynamic doping of positive electrode and interphase stabilization of electrodes.