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Raj and colleagues show that ERX-41 inhibits lipase-independent functions of LIPA and induces ER stress in different tumor types, providing a therapeutic strategy in PDX models of pancreas, ovarian and triple-negative breast cancer.

In Drosophila, FC2 neurons signal a navigational goal, which is compared with the fly’s heading by PFL3 neurons to guide moment-to-moment steering.

Kumari et al. show that host-derived extracellular vesicles capture systemic LPS and transfer it to the cytosol of immune cells via CD14-dependent endocytosis, triggering caspase-11-mediated gasdermin D activation and pyroptosis.

Neuroinflammation following intracortical microelectrode implantation impairs long-term brain-machine interface performance. Here, the authors developed a nanoparticle-based therapy that improves local hemostasis and delivers dexamethasone, reducing inflammation.

Gut microbiota contribute to the pathogenesis of ulcerative colitis (UC), but the molecular mechanisms are still unclear. Here the authors show that colonic fluid from patients with UC is enriched for bacteria extracellular vesicles (BEV) coated with host IgA, and that these IgA-coated BEV may activate CD89⁺ immune cells to aggravate inflammation and colitis in mouse models.

Exercise promotes recovery after stroke, but the underlying mechanisms are unclear. Here, the authors show that regulatory T cells enable exercise-induced repair by reducing neuronal hyperexcitability via interleukin-10, linking immunity to functional regeneration.

Coordination-induced bond weakening (CIBW) by redox-active metals is used to weaken bonds in water and ammonia to facilitate proton-coupled electron transfer but achieving CIBW using aluminium as abundant metal is challenging. Here, the authors report a system that uses aluminum with a redox non-innocent ligand to achieve CIBW of O-H and N-H bonds.

T-cell enrichment has attracted great interest but currently fails to fully replicate the complex natural immune interactions. Here, the authors report on magnetic polymerised antigen-presenting cells that mimic natural interactions to isolate rare tumour-reactive T cells, offering a platform for enhancing cancer immunotherapy and neoantigen discovery.

In this attempt at xenotransplantation of a lung from a genetically modified pig into a brain-dead recipient, although the grafted lung initially maintained viability and functionality, antibody-mediated rejection rapidly occurred, contributing to xenograft damage.

The optical properties of nanoalloys are complex and difficult to describe. Here, the authors use density functional and Mie theory to calculate the extinction of Au-Co and other nanoalloys of interest for quantum optics, magnetooptics, catalysis, and metamaterials.

Rainbow trout with depleted secretory IgM reveal interesting insights into the elusive role of this immunoglobulin in maintaining gut microbiota.

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.

A single dose of an adeno-associated virus vector encoding an HIV-1 broadly neutralizing antibody given shortly after birth results in persistent antibody expression and protection from infection in rhesus macaque models of human HIV-1 transmission through breastfeeding and sexual intercourse.

Therapeutic checkpoint for acute myeloid leukemia requires further investigations. The authors here identify ST2⁺ Treg cells facilitate AML growth by inducing CD8⁺ T cell depletion and exhaustion, while targeting ST2 by antibodies depletes ST2⁺ Treg cells and improves AML prognosis.

The regulatory mechanisms governing peptidoglycan-degrading autolysins remain poorly understood. In this work, Alvarez et al. show that lytic transglycosylase activity is inhibited by LD-crosslinks in Vibrio cholerae and other bacteria, providing resistance against predatory enzymes of both bacterial and viral origin.

In this work, authors study a molecular signature in STING protein that is critical for distinguishing activation from inhibition and demonstrates therapeutic potential in correcting STING-related mutations in autoimmune conditions like STING-Associated Vasculopathy with onset in Infancy (SAVI).

Thrombin-derived C-terminal peptides (TCPs) have anti-endotoxic functions in wounds by binding to bacterial lipopolysaccharide (LPS) and Gram-negative bacteria. Here authors use a spectrum of biophysical techniques to determine the conformation of a TCP in complex with LPS and define the interaction between TCPs and CD14.

Flies navigate to food sources by combining odour and wind-direction cues. This study identifies pathways to the fan-shaped body that encode these signals, and demonstrates how local neurons integrate odour- and wind information to guide navigation.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Current RSV vaccines induce immunity with limited durability in pre-exposed populations. Here, the authors generated an RSV preF self-amplifying RNA vaccine and show that a single dose induces potent innate, cellular, and humoral immunity in RSV-infected in naïve and pre-exposed non-human primates.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

Brain slices offer an experimental window into human neurophysiology. Using high-density microelectrode array recordings and adeno-associated virus–mediated optogenetics, the authors demonstrate that optogenetic targeting of CAMK2A+ neurons can affect network activity in human hippocampal slices.

Erosion rates and ice cover extent of present day fjords and summit plateau landscapes beyond the last deglaciation are virtually unknown. Here, the authors constrain the long-term denudation rates and glaciation history in west Greenland based on cosmogenic nuclides.

Ultrafast dynamics of laser ablation of gold in water revealed by pump-probe microscopy on a picosecond to microsecond timescale.

In this Review, the authors describe the bidirectional crosstalk between lysosome biology and immune cell function and polarization, focusing on immunometabolic reprogramming in the context of atherosclerosis and highlighting knowledge gaps and potential therapeutic strategies targeting immune cell lysosomes.

Somatic variants in certain genes can cause lesional focal epilepsy. Here the authors perform the largest somatic variant detection study in epilepsy to date, finding statistical support for 8 known and 2 novel genes, DYRK1A and EGFR, which may be potential biomarkers and druggable targets.

Results of a phase I/II clinical trial of CALEC, limbal epithelial cell grafts generated by an innovative and rigorously standardized manufacturing protocol, showing safety and feasibility for treating LSCD.

In a randomized placebo-controlled trial in 37 individuals with excess body weight, dietary supplementation with resistant starch lowers body weight and induces changes in gut microbiota composition. Mechanistic analysis in male mice shows that resistant starch at least partially facilitates weight loss through the action of Bifidobacterium adolescentis.