Search

Difelikefalin is an FDA-approved KOR-targeted drug for chronic pruritus yet exhibits side effects. Here, researchers solve cryo-EM structure of difelikefalin KOR-Gi, identifying Y320^7.43 as a key bias residue. Substituting D-Phe1 with β-phenylalanine develops beta01 which retains analgesic/antipruritic efficacy via a unique receptor conformation that reduces adverse effects.

Hybrid neural networks often underperform compared to conventional neural networks because of their low array utilization. Lu et al. propose a programmable spiking architecture that leverages photonic reconfigurable devices to integrate synaptic and neuronal functions without compromising performance.

Noise in optoelectronic memories causes harmful overlap of photoconductance states and degrades computing precision. Zhou et al. report an optoelectronic memory that achieves thousands of distinguishable states without denoising, enabling the detection of fast-moving objects.

Gene functional shifts can rewire molecular networks beyond expression changes. Here, authors present scDNS, which quantifies network divergence to infer gene perturbations and projects them to single cells, enabling sensitive detection of hidden regulation and heterogeneous responder states.

Current artificial vision systems suffer from high energy consumption and latency due to the von Neumann bottleneck and separated spatiotemporal processing. Wu et al. propose a vision system achieving native spatiotemporal co-processing with millisecond latency and 95% action recognition accuracy at low computational cost.

This study highlights a strategy to additively manufacture lightweight, strong, and ductile heat-resistant aluminum alloys. The partial solid-state amorphization of the nanoprecipitates during high-temperature tension offers an additional toughening mechanism.

Cell-type-specific 3D genome maps are hard to generate experimentally. Here, the authors develop Hi-Compass, a deep-learning framework that predicts chromatin interactions from accessibility data across variable sequencing depths, recovering chromatin loops and linking disease variants to target genes.

During lytic regulated cell death, a transitional agonal stage exists between initiation and terminal death. Here, the authors found that agonal cells upregulated uptake and internalization of extracellular vesicles fused with the cell membrane via SNARE complexes to enhance membrane repair.

Protein complexes are the machinery of life, yet mapping their structures across different species is challenging. This study presents an atlas of 1.1million cross-kingdom structures, revealing 181,671 high-confidence complexes that uncover new higher-order structures and evolutionary links.

NPM3 promotes histone lactylation (H3K18la/K27la) and drives FASN transcription and cardiomyocyte necroptosis in diabetic cardiomyopathy. Targeting this pathway with dihydroartemisinin alleviates cardiac dysfunction.

A genome-to-genome association study identifies host and viral risk factors that interact to drive nasopharyngeal carcinoma endemicity in southern China.

Soil acidification in China has reduced crop yields and increased cadmium contamination in rice. This study shows that although enhanced manure use can reduce acidification and rice cadmium in the short term, it increases long-term cadmium accumulation in soils, and meeting food quality standards requires reducing cadmium inputs from both manure and atmospheric deposition.

This study shows how the anti-cancer drug Actinomycin D blocks RNA polymerase II transcription and reveals why it preferentially targets CTG and CAG repeats, thereby providing a basis for modifying ACTD to target DNA repeat-associated disorders.

Autophagy has been reported to have an important role in glioblastoma temozolomide resistance but the underlying mechanisms are unclear. Here, the authors identify RFC4-STK38-BECN1 complex as a driver of autophagy activation and subsequent temozolomide resistance in preclinical models of glioblastoma.

The mid-infrared (MIR) range of the electromagnetic spectrum can be indirectly accessed by frequency upconversion. Here, authors propose a phase-matching-free scheme for broadband and efficient upconversion, covering wavelengths from MIR to ultraviolet with high-order harmonics generated from a NbOI₂ crystal. MIR imaging is demonstrated with a standard silicon camera.

PerturbFate is a high-throughput, cost-effective, single-cell platform that systematically profiles CRISPR interference perturbations to reveal common regulatory nodes and convergent phenotypic states across diverse genetic alterations linked to vemurafenib resistance in melanoma cells.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Bile acids, including glycocholic acid (GCA), have been associated to poor prognosis and cancer progression. Here, the authors discover that GCA inactivation of FXR reduces CD8 + T cell-mediated antitumor response in colorectal cancer.

Protein oligomerization can regulate cellular functions. Here, authors identify a small molecule that selectively induces WDR5 oligomerization using nanopore screening and show it disrupts cancer-driving interactions, highlighting a potential anti-tumor strategy.

Osteoarthritis is driven by epigenetic dysregulation, yet targeted therapies remain elusive. Here, the authors develop a cartilage-targeting hydrogel delivering BRD4-degrading PROTACs to suppress the BRD4- Nav1.7 axis and alleviate osteoarthritis.

Hydrogen can permeate two-dimensional crystals like graphene in the form of protons at high rates, involving catalytic dissociation and recombination steps, with permeability tunable by material type, metal nanoparticles, or atmosphere, offering insights for separation membranes and energy technologies.

The study presents NMR-Solver, an automated framework that determines small-molecule structures from NMR spectra by combining large-scale spectral matching with physics-guided optimization, enabling accurate and interpretable structure elucidation.

This study reveals that the brain encodes handwriting in multiple dimensions. The decoding paradigm, informed by movement data from healthy individuals, captures these full dimensions to enhance the performance of brain-to-text communication.

Grain number per panicle (GNP) is a yield-determining trait of rice. Here, the authors identify a GSK3-like kinase-encoding gene GNP2 and a bZIP transcription factor-encoding gene GNP5, demonstrating their synergistic regulation of GNP and showing that specific allele combinations of these genes enhance rice yield in field conditions.

The crystal structure of the CHS-CHIL complex reveals a gating mechanism that enhances CHS activity and specificity. This conserved regulatory paradigm, validated by engineering a CHIL variant, offers strategies to improve flavonoid production in plants.

The authors report a wavelength-gated regeneration strategy, where specific wavelength photogenerated carriers drive the reversible cycling of active sites, enabling highly stable photocatalytic CO₂ reduction to C₂H₆.

A sequential deposition method combined with a multifunctional organic additive enables sky-blue all-thermally evaporated perovskite light-emitting diodes with a peak external quantum efficiency of 20.15%, as well as their integration into an active-matrix display prototype.

The authors present a multi-core neuromorphic architecture that enables energy‑efficient training of deep spiking neural networks via backpropagation. The design features a multi-engine core, multi-level parallelism, sparsity optimization, and FPGA validation.

Yu et al. report a self-assembled heterogeneous microstructure consisting of chiral-deficit grains and chiral-rich grain boundaries in chiral perovskite with the former as in-plane spin valves for spin selection. Retinomorphic sensor arrays based on the chiral perovskite film enable binocular artificial visual systems.

Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

Metabolic profiling of extracellular vesicles for diagnostic applications remains challenging. Here authors develop ACTIVITY, a cascade-catalysis strategy to detect metabolically active extracellular vesicles, enabling macrophage phenotyping and differentiation of pneumonia patients from healthy controls.

In this study, the authors identify an Aurka–Bhlhe41 axis, which prevents microglia from aging-like dysfunction by limiting CD22 upregulation, preserving myelin debris clearance and remyelination, and highlighting a potential therapy target for neurodegeneration.

Both endogenous and exogenous signaling pathways are involved in the maintenance of self-renewal and pluripotency of human embryonic stem cells (hESCs). Here, the authors uncover that endogenous VEGF signaling safeguards pluripotency and prevents extra-embryonic differentiation in primed hESCs via activation of transcription factor NANOG and suppression of BMP signaling activity.

Lesion-targeted immune modulation is a feasible strategy to control cardiac fibrosis, and engineered dendritic cells are a promising therapeutic platform for treating cardiac remodelling and heart failure.

Inborn errors of cell death (IECD) with autoinflammatory manifestations could be induced by excessive T cell death. Here the authors characterize IECD patients with autoinflammatory manifestations who possess overactive RIPK1 variants which promote T cell death, secretion of TNF and IFN-γ along with activation of monocytes and macrophages which promotes further autoinflammation.

C-14 hydroxyl group is critical for the function of ent-kaurane diterpenoids (ent-KTs). Here, the authors report discovery and engineering of bacterial P450s for C-14 hydroxylation in ent-KTs.

High-performance battery materials often degrade during standard cleaning processes. Here, the authors identify why water washing causes structural collapse in sodium-based oxides and demonstrate that ethylene glycol can safely remove impurities while maintaining the material’s integrity.

He et al. report that the host-derived macrophages/monocytes enhanced malaria transmission by reducing the abundance of transmission-blocking microbiota in mosquito midgut via SRA-mediated phagocytosis. In addition, the depletion of macrophages/monocytes or the use anti-SR-A neutralizing antibodies significantly enhances the transmission-blocking efficacy of anti-Pfs25 monoclonal antibodies.

Total internal reflection structural colors often lack dynamic response. Here, the authors develop Janus droplet systems with dual surfactant/temperature responsiveness, creating cold-chain labels to monitor pharmaceutical freeze history via color changes.

The oxygen evolution reaction is hindered by slow proton transfer. Here, the authors report an ordered oxygen-down water layer that accelerates initial water deprotonation and proton transport, enabling low-voltage, durable membrane electrolysis at high current.

Dielectric materials with both high dielectric constant and wide bandgap are sought after for the miniaturization of 2D transistors. Here, the authors report the characterization of dielectric KBe₂BO₃F₂ nanosheets with a band gap of > 8 eV and a bulk dielectric constant of 63, showing their application for the realization of high-performance 2D MoS₂ transistors.

Conventional dendritic cells (cDCs) are essential to generate effective anti-tumor immune responses; however, they are often dysfunctional within the tumor microenvironment. Here the authors report that the impaired function of cDCs in late-stage tumors is associated with a reduction of pentose phosphate pathway (PPP), suggesting strategies to augment PPP as a therapeutic option to increase cDC-mediated anti-tumor response.

Elevated exposure to 4-hydroxyphenanthrene (4-OHPhe) is positively associated with obesity risk. Here, the authors show that exposure to 4-OHPhe downregulates expression of hydroxylamine reductase genes in Bacteroides uniformis, leading to altered gut microbiota-bile acid-FXR axis and suppression of adipose thermogenesis.

LHAASO has detected γ-ray emission with a spectrum extending to 2 PeV from the pulsar wind nebula (PWN) powered by PSR J1849-0001, indicating an extreme particle acceleration efficiency and challenging the current particle acceleration theories.

Grain number per panicle (GNP) is a critical yield component trait of rice. Here, the authors clone a MAPKKK encoding gene GNP3 positively regulating grain yield and show its role in rice panicle development by interacting and destabilizing ethylene biosynthesis related enzyme SADENOSYLMETHIONINE SYNTHETASE 1.

Systemic lupus erythematosus (SLE) is a complex autoimmune condition and treatment options have limited efficacy. Here, by analysis clinical samples and employing preclinical models, the authors show that cGAMP levels are elevated in the plasma of patients with SLE and that loss of cGAS ameliorates symptoms in an imiquimod-induced lupus model. Importantly, they identify prasugel as a cGAS inhibitor with promising therapeutic potential.

Nociceptive hypersensitivity and prolonged wound healing due to the interaction of peripheral neuropathy and local immune disorders hinder the regenerative repair of diabetic foot ulcer. Here, the authors report a low-intensity focused ultrasound-activated piezoelectric gel bandage with immune homeostasis modulation and neuropathic pain relief functions for comprehensive repair of diabetic wounds.

Neutrophils are known to be important in COPD pathogenesis and calcium signaling is involved in this process. Here the authors examine the function of Na⁺Ca²⁺ exchanger 1 (NCX1) in neutrophil function in mouse models of chronic cigarette smoke exposure and show that inhibition of NCX1 reduces neutrophil accumulation in the lungs and formation of neutrophil extracellular traps (NETs).

Covert mortality nodavirus, a pathogen previously known to cause important losses in shrimp aquaculture, is identified as being a potential causative agent of an emerging and severe ocular disease in humans, specifically presenting as persistent ocular hypertensive viral anterior uveitis.