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Limited improvement of systemic therapy has been achieved in first line treatment for advanced Biliary tract cancer (BTC). In this randomized phase 2 trial on BTC, the combination of sintilimab, anlotinib, and gemcitabine/cisplatin demonstrated an improvement in progression - free survival (PFS) and objective response rate (ORR) while reducing the risk of disease progression compared to chemotherapy monotherapy.

A synthetic biology approach was used to engineer Vibrio natriegens into a strain capable of bioremediating complex organic pollutants in saline wastewater and soils, thereby addressing notable threats to marine biosecurity.

A β-GalNAc-O-tyrosine glycopeptide co-assembles with Aβ42 into distinct fibrils, reducing toxic oligomers and neurotoxicity in cells and an Alzheimer’s disease mouse model, suggesting a new modality to modulate amyloid aggregation.

The synthesis of N-CF₃ amides is of great interest, but the direct preparation of these compounds via established amidyl radical chemistry remains underexplored. Here, the authors report the synthesis of N-(N-CF₃ imidoyloxy) pyridinium salts and demonstrate their utility as trifluoromethylamidyl radical precursors in photocatalytic trifluoromethylamidation reactions.

The microglia–neuron interactions contributing to neuronal hyperexcitability are unclear. Here, the authors show how GABA and C3 signaling coordinate microglial engulfment of inhibitory synapses, driving excitatory–inhibitory imbalance and neuronal hyperexcitability in epilepsy.

SFTS is an emerging tick-borne disease with high mortality rates caused by the SFTS virus. Here, the authors identify LRP1 as an entry factor for SFTSV, show that SFTSV glycoprotein Gn interacts with LRP1 and that blocking LRP1 reduces viral infection and improves survival in lethal mouse models.

Targeted deletion of integrin-associated protein CD47 enhances long-term engraftment of human CD34⁺ cells in immunodeficient pigs lacking IL2RG and RAG2, enabling large-scale production of functional human immune cells.

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

Bellman equation is widely applied in solving dynamic optimization problems. Here, the authors present a memristive Bellman solver reducing the computational complexity and improving energy efficiency for advanced decision-making process.

VISA/MAVS is the central adaptor in antiviral innate immunity, yet the assembly of VISA signalosome is unclear. This study reveals that PWWP3A competes with TRAF6 for binding to VISA, impeding the recruitment of TBK1 and subsequent IRF3 activation, which prevents excessive immune responses.

Yuan et al. report a nearly vertical subthreshold swing field-effect transistor consists of a graphene/silicon heterojunction drain and a silicon channel. The device enables nearly hysteresis-free transistors with subthreshold swing of 16 µV dec⁻¹, and a complementary logic inverter with gain of 311.

Here, trace detection of NO2 is achieved with a 2D Schottky-junction Bi₂O₂Se gas sensor. Simultaneous signals allow for detection in the ppt range, and impedance angle analysis allows for molecular specificity.

The prevalence of mutations that can predispose to pancreatic adenocarcinoma (PDAC) remains unclear, especially in underrepresented populations. Here, the authors create a germline mutation map of 1,123 Chinese PDAC patients and compare them to cohorts from other populations, finding CFTR as a potential driver.

The development of hole-selective contacts for Sn-based perovskite solar cells is highly desirable. Here, the authors report self-assembled monolayers with oligoether side chains on the benzothiadiazole unit and achieve an efficiency of 28.61% for operationally stable all-perovskite tandems.

Biomolecular condensates play essential roles in regulating physiological events in biological systems, and while multiphasic condensates have been studied, condensates derived from a single component of short peptides were not reported. Here, the authors present the symmetrical core-shell structural biomolecular condensates formed with a programmable tetrapeptide library via phase separation, and show that tryptophan is key for core-shell structure formation.

Piracetam improves wide-bandgap perovskite crystallinity and uniformity, enabling monolithic all-perovskite tandem solar cells with efficiencies of 28.71% (0.07 cm²) and 28.20% (1.02 cm²), ensuring minimal efficiency loss during scale-up.

Body plan complexity is associated with the number of different cell types, yet the processes that create this diversity are unclear. Here the authors use transcriptomics to test the hypothesis that unlike cancer cells, novel normal cell types arise through sub-specialization of an ancestral cell type.

Existing method struggles with CHH methylation detection from the reads generated by the latest ONT technology. Here, the authors developed a deep learning model that can significantly improve CHH detection accuracy in plants.

Graphene is known to display unique functional properties due to its two-dimensional structure. Here, the authors measure the thermal conductivity of suspended graphene as a function of sample length, finding that thermal conductivity is higher in longer samples as a result of two-dimensional phonons.

The development of catalysts for practical asymmetric hydrogenation of ketones remains an important goal of synthetic organic chemistry. Here, an anionic iridium catalyst with excellent activity is reported and used in a hundred-kilogram-scale reduction as part of a route to chiral nicotine.

Deletion of upstream tumor suppressors of the Hippo/YAP pathway is frequent in papillary renal cell carcinoma (pRCC). Here, the authors employ a transgenic mouse model, single-cell transcriptomics and public genomic datasets to show that targeting hyperactivated YAP1 prevents neoplastic renal epithelial cell immune evasion and impairs the development of pRCC.

The connection between amino acid metabolism and pyroptosis remains elusive. Here, the authors show that the methionine metabolite spermidine inhibits GSDME-mediated pyroptosis by dampening GSDME-NT endocytosis, which can be targeted to promote anti-tumor immunity.

A quantum microsatellite, with a payload weighing only 23 kilograms, in combination with portable ground stations that weigh merely 100 kilograms, is capable of performing space-to-ground real-time quantum key distribution.

The structures of the open and closed states of the Omicron spike protein and its complex with the ACE2 receptor or a broadly neutralizing antibody are resolved and shed light on the receptor engagement and antibody neutralization of Omicron.

Here, the authors provide insights into the conformational dynamics of the Beta and Kappa SARS-CoV-2 spike (S) proteins by determining their cryo-EM structures, which revealed a distribution shift towards the open state for both variants compared to the wild-type S protein. They also present the structures of the Kappa and Beta S-ACE2 complexes, where a population shift towards the three receptor-binding ___domain up conformation was observed. In combination with biochemical data these structures show how the S protein variants efficiently recognize and bind to ACE2.

Here, the authors report immunogenicity and safety of AR-MPXV5, a penta-component mRNA vaccine, in naive and simian immunodeficiency virus infected nonhuman primates (NHPs), and demonstrate protection in naïve male NHPs after immunization with two doses of AR-MPXV5.

A point mutation in the phosphoribosylpyrophosphate synthetase gene is found to rewire C1 metabolism and thereby enhance colonization capabilities and growth-promoting effects in plants. The effect of this mutation is prevalent across Methylobacterium strains.

The theory-guided synthesis of a tungsten-based W₂TiC₂T_x MXene from a non-MAX nanolaminated ternary carbide (W,Ti)₄C_4−y is reported. The tungsten-rich basal plane of the W₂TiC₂T_x MXene is then examined for the electrocatalytic hydrogen evolution reaction using a combined experimental and theoretical approach.

Biobanks of genetic data have been primarily in European populations, which gives us an incomplete understanding of complex traits across populations. Here, the authors initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole genome sequences and 5,841 high-density genotypes from China, characterizing large-scale genomic variation in Chinese populations.

Efficient synthetic pathways to geminal dihalides are quite limited, despite their versatility as chemical building blocks. Here, the authors report a photo-mediated deconstructive fragmentation of cyclic and acyclic trisubstituted alkenes to access a variety of geminal dihalides.

Radial spokes (RS) are crucial in coordinating ciliary motility. Here, authors use cryo-EM and cryo-ET to gain insight into mammalian RS divergence in ependymal cilia, RS assembly mechanism and the structure-function relationships of ciliary and flagellar axonemes.

The power conversion efficiency of wide-bandgap pure-sulfide kesterite is low. Wang et al. propose annealing in a hydrogen-containing atmosphere and report the underlying mechanism that enables a certified efficiency of 11.4%.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Natural materials with highly oriented and heterogeneous structures often have favorable materials properties, but such structures are challenging to replicate in artificial materials. Here, the authors report the development of hierarchically aligned heterogeneous hydrogels with toughness and strength.

Chen, Hu, Zhao, Fang and colleagues show that the ribosomal large subunit protein Rpl12 functions as a conserved ribophagy receptor in multiple organisms.

Aspirin is a potent lysine acetylation inducer, but its impact on lysine ubiquitination and ubiquitination-directed protein degradation is unclear. Here, the authors show that aspirin impairs proteasomal activity, affecting the degradation of soluble proteins, and induces K63-linked ubiquitination to promote the clearance of insoluble protein aggregates.

Lymphatic vessels are vital in the musculoskeletal system, but their role in bone repair is unclear. Here the authors found early lymphatic drainage insufficiency in fractures impacts osteoblast survival and stem cell proliferation by modulating the hematoma niche via DAMP transport.

The complexity of carbohydrate structures makes their synthesis challenging. Now, an automated glycan synthesizer is reported which is capable of preparing a library of bioactive oligosaccharides, including a fully protected fondaparinux pentasaccharide. Furthermore, the synthesizer can rapidly assemble arabinans up to 1,080-mer size, starting from monosaccharide building blocks.

Transformations of alcohols, which are ubiquitous in chemistry and are native functionalities in many natural products and bioactive molecules, are cornerstones of organic synthesis. Here the authors describe photocatalyzed cross-couplings of activated alcohols with α-amino acids, providing a direct approach for a variety of unnatural amino acids.

2D high-κ dielectric materials remain highly sought-after for the future development of 2D electronics. Here, the authors report a 2D edge-seeded heteroepitaxial growth strategy to synthesize CaNb₂O₆ thin films with equivalent oxide thickness down to 0.7 nm and show their application for high-performance 2D MoS₂ transistors.

A sequence of a Diels–Alder reaction and oxidation is a powerful route to valuable aromatic compounds. Here, the authors report a more atom-economical oxidant-free strategy involving a Diels–Alder with H₂ evolution under noble-metal-free photoredox conditions.

Lysosomal storage disorders (LSDs) are severe genetic diseases currently without routine therapies. Here, the authors identified that SNX8 participates in lysosome reformation and serves as a potential drug target for new therapies to treat LSDs.

Intestinal TM6SF2 is found to interact with fatty acid-binding protein 5 to modulate the secretion of fatty acids and the composition of the gut microbiota, thereby protecting against metabolic dysfunction-associated steatohepatitis.