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Multiplexed editing using Cas12a transgenic mice facilitates the study of disease models with complex genotypes.

The authors proposed a multi-task deep learning model, to accurately predict drug-target affinity and generate target-aware drugs. In the proposed model, the authors developed the FetterGrad algorithm to mitigate gradient conflicts between both tasks. Through comprehensive experimentation, the authors have shown, that their proposed model effectively predicts affinity and generates target-aware drugs thus enhancing the drug discovery process.

The molecular mechanisms underlying the function of different cellular states in glioblastoma stem cells (GSCs) remain poorly understood. Here, the authors perform integrated single cell and bulk analysis of GSCs and identify potential therapeutic targets.

Here, the authors fabricate hybrid van der Waals heterostructures based on 2D tessellations of DNA origami thin films, graphene and boron nitride, showing that the DNA films can induce periodic superlattices at the interface and modulate the electronic properties of the samples.

Using single-cell and spatial molecular profiling of infarcted mouse and human hearts, Li, Ni, Wang and colleagues identify a subset of cardiac fibroblasts expressing CD248 that plays a critical role in fibroblast–T cell interaction, and show that disrupting this interaction with monoclonal antibodies or anti-CD248 chimeric antigen receptor T cells results in reduced cardiac fibrosis and improved function.

Hydrogels are essential for stem cell-based tissue regeneration but struggle with hard tissue repair. The authors report a shell-hardened macroporous hydrogel with spatiotemporally programmed mechanics to enhance stem cell-driven bone regeneration.

The microbial processes involved in deep sea phosphorous cycling are unclear. Here, the authors develop a deep learning model, LucaPCycle, identifying alkaline phosphatase families and archaea that contribute to phosphorous cycling in deep sea cold seeps.

Socioeconomic status is multidimensional and can change over time. Xu, Lui, Ji et al. found dimension-specific, late-stage-specific and change-specific socioeconomic effects on brain, cognition, personality and emotion.

Sexual dimorphism is a feature of many cancers, but how this functions is often unclear. Here the authors show that in bladder cancer it is regulated by a microbiota–lurasidone–LCN2 circuit that controls the accumulation of a subpopulation of senescence-like neutrophils.

Anxiety involves abnormal respiratory responses to emotional stimuli. Here, the authors show that CeA^GABA neurons, acting as a central hub, are instrumental in orchestrating anxiety-like behaviors and breathing patterns through the CeA-PVT and CeA-LPBN-preBötC circuits, correspondingly.

Wireless bioresorbable stimulators are promising therapeutic implants that naturally dissolve after use. Here, the authors developed a device that operates for months and enables simultaneous multi-site stimulation, preventing early muscle atrophy and accelerating reinnervation in nerve injury models.

Global consumption drives freshwater overuse at production sites along supply chains, of which 24% is outsourced via trade. Agricultural demand is a key driver, while manufacturing exports exacerbate water stress in emerging economies.

The formation of organelles was a pivotal point in eukaryotic evolution. Here they show that Archaea possess Arf-like GTPases that can perform key organelle-producing mechanisms when expressed in a eukaryotic cell, laying the foundation for the evolution of endomembrane organelles.

Sun, Fu, Zheng, Hong, Liu et al. generate a single-nucleus transcriptomic atlas of the primate cochlear aging, identifying an age-related decline in Slc35f1 and showing that silencing Slc35f1 in mice induces hair cell degeneration and auditory deficits.

SIRT5 protects against primate skeletal muscle ageing through TBK1 desuccinylation, which inhibits the downstream inflammatory and senescent phenotypes.

Residual stresses are pervasive in most modern plastics. Here, the authors show that they promote the migration of low-molecular-weight amorphous polymer and additives from bulk plastics and release micropollutants into water.

Malignant pleural effusion is a challenge for cancer therapy. Here, the authors report on a piezoelectric nano-system that inhibits tumor growth in the thoracic cavity by piezo-generated reactive oxygen species using the intrapleural pressure, triggering immunogenic cell death, to treat malignant pleural effusion.

The authors report the large low-field-driven electrocaloric effect in the novel organic-inorganic hybrid TMCM-CdCl₃, underlyingly from the disordering of organic cations and the low-symmetry interaction induced two-step meta-electric transition.

Kinematic sensors are required in many industrial applications, but the current sensor designs rely on power input from external sources. Here, Jing et al.harness the micro-meso scale ambient energy via a triboelectric generator to self-power sensors for one- and two-dimensional motion vector sensing.

Nuclear RNA decay regulates gene expression in cultured cells, but its role in animals is largely unclear. Here, authors found that the nuclear exosome co-factor MTR4 functions in shaping the transcriptome for meiosis initiation and male fertility.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Anlotinib hydrochloride is a multi-target tyrosine kinase receptor inhibitor, previously combined with anti-PD1 as therapeutic strategy for several cancer types. Here the authors report the results of a phase II trial of nivolumab (anti-PD1) plus anlotinib hydrochloride in patients with advanced gastric adenocarcinoma and esophageal squamous cell carcinoma.

ABA signaling is found to modulate global mRNA translation efficiency. GRP7 associates with ribosomes and directly binds to its target mRNAs. ABA suppresses GRP7&8 protein levels via its core signaling components and decreases global mRNA translation efficiency.

Oligomers are among the various chemical contaminants that can derive from the breakdown of microplastics and that are challenging to detect. A purposely designed platform allows detection of a large number of oligomers, providing an important step towards their risk assessment.

Radiation-hardened electrostatic dielectric capacitors are critical components in advanced electronic and electrical systems. Here, the authors demonstrate a high-energy-density and radiation-tolerant capacitor by constructing a dendritic-like structured ferroelectric embedded in an insulator.

Dielectric materials with high energy storage performance are desirable for power electronic devices. Here, the authors achieve high energy density and efficiency simultaneously in multilayer ceramic capacitors with a strain engineering strategy.

Gut microbiota-derived succinate promotes CitC succinyltransferase-dependent succinylation of PurR to alleviate T3SS repression and promote virulence in enterohaemorrhagic Escherichia coli and Citrobacter rodentium.

In a multicenter randomized phase 3 trial, stapokibart, a humanized monoclonal antibody that targets IL-4R alpha, significantly improved daily nasal and ocular symptom scores during the pollen phase in patients with moderate-to-severe seasonal allergic rhinitis.