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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.

Long-persistent afterglow can be achieved in organic materials, but understanding of the processes is limited. Here, the authors report the study of acceptor matrices with dopants for insight into energy transfer processes.

Shallow NV centers in diamond are promising quantum sensors but suffer from reduced coherence times due to surface spin impurities. Here the authors improve coherence times to over 1 ms through interface engineering by oxygen-terminating the diamond surface and patching it with graphene.

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.

Glioma stem-like cells (GSCs) contribute to therapeutic resistance via enhanced capability of DNA damage repair. Here the authors identify that the upregulated transcription factor AATF in GSCs modulates the stability and release of XRCC4 protein to promote DNA repair and resistance to radiotherapy.

Acrolein, a byproduct of polyamine metabolism and chemotherapeutic agents, is also found in cigarette smoke. Here the authors report that acrolein mediates spermine-induced ferroptosis, while in ferroptosis-resistant cancer cells, acrolein suppresses necroptosis by inhibiting the oligomerization of MLKL, contributing to chemotherapy resistance.

While the STING-type-I interferon pathway plays a key role in anti-tumour immunity, current direct STING agonists have limited therapeutic benefit. Here, the authors identify ENPP1 as a safer and more effective STING-modulating target than direct STING agonism, and use an AI-based drug design platform to design the ENPP1-selective inhibitor ISM5939.

This study presents an oral CRISPR–Cas9 delivery system that precisely disrupts the TRAP1 gene in colorectal cancer, enhancing chemo-immunotherapy with robust antitumour effects.

Here, based on single-pass intestinal perfusion platform, the authors establish a microbiota-based drug permeability screening framework to compare perfusion and metabolomic profiles of 32 orally administered drugs in germ-free rats, and show that increased permeability of N-Acetylcysteine is mediated by cysteine-3-ketosphinganine of Bacteroides.

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.

Developing artificial bulk materials that seamlessly integrate rigid inorganic components with ductile organic constituents is vital for replicating the mechanical properties of natural biological composites but elusive. Here, the authors report a calcium phosphate-based inorganic-organic hybrid metamaterial that seamlessly integrates the functional traits of inorganic and organic constituents.

A novel covalent inhibitor, ISM3312, targets the main protease of multiple human coronaviruses, including drug-resistant strains, and shows broad antiviral activity. It offers a promising therapeutic strategy against current and future coronavirus threats.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

The mechanism underlying YAP/TAZ transactivation remains to be explored. Here the authors report that the hydrophobic transcriptional activation domains of YAP/TAZ exert dual functions on transcriptional initiation and elongation through interactions with TAF4 and MED15, which could be targeted for anti-cancer therapy.

Here Tai et al. unveil elevated formation of the C-terminal binding protein (CtBP)–tripartite-motif-containing protein 28 (TRIM28) complex in breast cancer cells and mutual protection between CtBP and TRIM28. This complex is required for mammary gland development and its high levels lead to breast cancer metastasis by repressing autophagy.

The stability of deep-blue phosphorescent organic light-emitting diodes is critical for commercialization. Here, the authors employ a deuterated exciplex-forming host, achieving largely improved lifetime of 370 and 557 h with blue-shifted colours.

The dynamic kinetic asymmetric C−O cross-coupling has presented significant challenges and remains unexplored. Here, the authors report the dynamic kinetic asymmetric C−O cross-coupling of oximes and phenols via copper/BOX-catalysed enantioselective O-arylation with diaryliodonium salts.

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 analyzed 2923 plasma proteins through prospective cohort and genetic analyses, identifying IL12B, CD6, MXRA8, CXCL9, IFNG, CCN3, RSPO3, and IL18 as prioritized potential therapeutic targets for inflammatory bowel disease, offering insights into its mechanisms and treatment.

Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases, but its relationship with MAFLD remains unclear. Here, the authors show that SR-A3 is an important modulator of hepatic energy metabolism and is a potential therapeutic target against MAFLD.

Cheng et al. identify a mitochondrial complex IV (CIV) deficiency in the brains of patients with sporadic amyotrophic lateral sclerosis (ALS). They demonstrate that defects in mitochondrial CIV induce ALS-like phenotypes in rats and highlight CIV deficiency as a potential risk factor and therapeutic target for ALS.

Cerebrospinal fluid circulating tumor DNA profiling had prognostic value in a cohort of 584 patients with lung cancer and central nervous system metastases, and could be used to inform personalized therapies.

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.

Quantum simulation has the potential to enable experimentally studying problems which are not directly tractable in a laboratory or computationally. Here, the authors simulate the Majorana equation with a ytterbium ion, which requires them to simulate antiunitary and therefore unphysical operations.

Oxidative stress contributes significantly to postmenopausal osteoporosis by impairing osteoblast function, but its precise mechanisms remain unclear. Here, the authors show that estrogen deficiency reduces GPX4 expression, leading to phospholipid peroxidation that impairs osteoblastogenesis, while GPX4 activators including 6- and 8-Gingerols can mitigate these effects.

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.

Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy, for which the underlying pathological mechanisms are still poorly understood. Here, the authors show that AGGF1/TNFSF12/FN14 signalling pathway regulate the pathological angiogenesis of ischaemic retinopathy

This work focuses on the characterization of CLE peptide gene, revealing how the TaCLE24b-TaCLV1 signaling cascade together with TaSG-D1 modulate lateral root development and drought stress tolerance in wheat.

To overcome limitations with anion dissolution, the authors design 2D FeTeSe nanosheets as electrocatalyst. The reaction-driven, in-situ generation of anisotropic in-plane tensile and out-of-plane compressive strains enhances the alkaline low-concentration nitrate reduction.

Here the authors use cryo-electron microscopy to provide insights into fatty acid recycling by an acyl-acyl carrier protein (ACP) synthesizing enzyme, showing a transition from a hexameric to tetrameric form in the process of acyl-ACP production.

This work introduces the free-energy machine (FEM), which combines statistical physics principles and machine learning techniques to solve various combinatorial optimization problems. FEM outperforms state-of-the-art algorithms in both efficiency and effectiveness across multiple combinatorial optimization problems, demonstrating its broad applicability.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

Industrial and agricultural activities, such as mining, smelting and farming practices, have led to widespread arsenic pollution in Chinese soils and may threaten the viability of future rice production. Ambitious mitigation measures beyond those already undertaken by the Chinese government are needed to reverse these increasing impacts.

Biohydrogen production technologies effectively use waste biomass resources and produce high-purity hydrogen. Here, authors present and evaluate a continuous pilot-scale biohydrogen production system based on spectrum coupling, thermal effect, and multiphase flow properties of hydrogen production.

Shen et al. identify a noncanonical role for the inflammasome protein NLR family CARD ___domain-containing protein 4 (NLRC4) to attenuate tumor development. NLRC4 forms a scaffold to assemble the ataxia telangiectasia and Rad3-related DNA repair complex and the repair kinase checkpoint kinase-1 to promote repair of DNA breaks.

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.

Fluorescence microscopy can be exploited to visualize and study T cell mediated cytotoxicity. Here the authors describe a high-throughput Bessel oblique plane microscopy platform for 3D imaging and phenotyping of cytotoxic CAR-T cells in co-culture with cancer cells.

Lithocholic acid is one of the metabolites upregulated during calorie restriction, and treatment of mice, worms and flies with this bile acid alone can reproduce the health benefits of calorie restriction.

Endothelin-1 activation after SARS-CoV-2 infection leads to vascular permeability, chondrocyte senescence, osteoclast activation and cyst formation in affected joints of hamsters, which can be alleviated using macitentan. Joint injury was also seen in two patients after COVID-19 infection.

Whether PD-1 splicing isoforms impact T cell anti-tumor capacity has not been fully illustrated. Here the authors identify a human PD-1 isoform, PD-1^28, which functions to suppress anti-cancer immunity in vitro and in both syngeneic and humanized mouse tumor models.

In this prespecified analysis of the ongoing TORCHLIGHT phase 3 trial, first-line treatment with toripalimab and nab-paclitaxel in patients with advanced triple-negative breast cancer led to significantly longer progression-free survival in the PD-L1-positive population compared to nab-paclitaxel alone.

Difficulties in propagating HRV-C have hindered our understanding of this common respiratory pathogen. Here, authors developed an organoid-based system to reproducibly propagate HRV-C and characterized HRV-C infection in physiologically active respiratory organoids.

Searching non-charge-based devices is crucial for sustainable information processing. Here, the authors make a nonvolatile magnon field effect transistor at room temperature, enabling efficient magnon transport control via the gate voltage pulses.