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(+)-Pleuromutilin is a structurally intricate natural antibiotic featuring a densely functionalized 5/6/8 tricyclic core and eight contiguous stereocenters. Here, the authors report a bioinspired total synthesis of (+)-pleuromutilin and (+)−12-epi-mutilin from (+)-pulegone in 18 and 16 steps, respectively.

Chen et al. report a crystal regulation strategy for 3D perovskites by using functional molecule to adsorb to specific perovskite facets and diminish random crystal facet-correlated defects, yielding pure-blue LEDs with emission peak at 473 nm, linewidth of only 14 nm, and efficiency of 14%.

The authors identify Npr1 as a nucleophagy receptor in fission yeast that acts redundantly with Epr1 to degrade nuclear components. Tethering chromatin to the inner nuclear membrane blocks nucleophagy, suggesting a genome protection mechanism.

Molecular devices offer the potential for the scalability and energy efficiency required to develop energy-sustainable AI. Zhang et al. report a single-molecule neuromorphic device that consumes 6.34 aJ per operation and support both short-term to long-term memory, featuring over 10 distinct conductance states.

Here, in mouse models of GMPPB dystroglycanopathy, the authors show that impaired glycosylation disrupts muscle integrity and triggers broader cellular stress. They identify actionable pathways that improve muscle function, suggesting therapeutic strategies.

CBP phosphorylation keeps intestinal homeostasis by restraining CBP–p53 binding to allow sufficient versican expression. Its impairment suppresses versican, disrupting the stem cell niche to drive UC and highlighting versican as a therapeutic target.

Treatment failure exists in Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. Here this group reports a phase 2 randomized trial evaluating the efficacy and safety of adding nimotuzumab, to CCRT on 246 patients with untreated, non-keratinising, stage II–IVA LA-NPC.

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).

Methicillin-resistant Staphylococcus aureus (MRSA) is a key pathogenic bacterium and poses a significant therapeutic challenge due to its developing resistance to therapeutics. Here the authors establish a role for the MRSA virulence factor phenol-soluble modulin α3 in promoting macrophage M1 polarization and necroptosis via the host receptor FPR2 and the ISGF3 complex, and suggest the use of fludarabine to target the STAT1 component of this axis in models of MRSA infection.

The COMPASSION16 trial showed survival benefits of cadonilimab plus standard therapy in advanced cervical cancer. Here, subgroup analysis confirms consistent progression-free and overall survival improvements across diverse patient profiles.

Au nanowires with an unconventional hexagonal close-packed (4H) phase stabilize the 4H-phase high-entropy alloys grown epitaxially on their surface through a facile chemical synthesis. The resulting core–shell nanostructures demonstrate promising overall water electrolysis performance.

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.

The impact of cooling through the Eocene-Oligocene transition on the marine biosphere is not well constrained. Here the authors construct a high-resolution record of foraminiferal species richness history spanning this transition that reveals differential diversity trends depending on foraminiferal habitat and life mode.

SERS analysis at higher temperatures, such as during photothermal processes, is challenging due to enhancement losses. Here, the authors demonstrate a heat-induced increase in SERS activity mechanistically attributed to assisted hot-hole transfer.

FRIL is an antiviral legume lectin that recognizes complex type N-glycans. Here, authors discover a process to activate the inert recombinant lectins, and engineer a shift of FRIL’s glycan recognition to high mannose N-glycans.

Cancer stem cells contribute to cancer evasion and relapse by suppressing the immune response. Here, the authors identify sterol O-acyltransferase 1 (SOAT1) as a cancer stem cell immune checkpoint and propose that SOAT1 inhibition results in oxysterol-mediated reprogramming of intratumoral regulatory T cells via a trans-cellular 20SOHC-GPR132, ultimately enhancing anti-tumor immunity in various preclinical mouse models.

Antifungal aureobasidin A (AbA) targets inositol phosphorylceramide (IPC) synthase. The authors trap its ceramide-bound and drugbound states, revealing the catalytic and drug-inhibition mechanisms, providing basis for antifungal drug development.

Leveraging multi-element symbiosis, protective interfacial nanolayers are engineered in an intermetallic alloy. This results in a high fatigue limit of ~1,100 MPa, far exceeding that of conventional intermetallic alloys.

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.

Turning methane into methanol with H₂O₂ is hard because reactive oxygen is difficult to control. Here, Fe and Cu atoms placed in different regions of a zeolite guide oxygen chemistry, boosting methanol yield and selectivity while limiting overoxidation.

Mechanistic modeling of scoliosis sheds light on the role of the exosome-mediated high cholesterol flow between spinal cartilage and bone tissue in the context of progression of scoliosis.

Oversimplified synthetic wastewater misjudges fouling drivers and distorts economics. This study reveals that organic synergies counterintuitively mitigate membrane fouling, advocating for compositional fidelity to bridge lab-industry gaps.

A dated phylogeny of 16,585 vascular plant species native to China reveals three major centres of endemism, including a potential new global biodiversity hotspot.

Ruan and colleagues show that vascular resident macrophage-derived Sparcl1 has a protective effect during aorta aneurysm progression by interfering with FGF2-induced dysfunctional lymphangiogenesis, TLS formation and immune cell recruitment.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

Reconfigurable chip-to-free-space interfaces based on thin-film lithium niobate microrings generate on-demand nonlinear structured light, including tunable optical vortices, optical skyrmions and spatiotemporal vortex pulses.

The development of Tat clusters has advanced the intracellular delivery of functional antibodies at low concentrations, but the variety of proteins that can be successfully delivered remains limited. Here, the authors report that by reversibly modifying the surface of functional proteins with anionic peptides, various protein cargoes (otherwise difficult to deliver) can be delivered into living cells by synergetic electrostatic interactions with the cationic cell-penetrating peptide clusters TAT₃.

Dong and colleagues report that blockade of T cell-expressed cytotoxic and regulatory T cell molecule results in selective mitigation of immune-related toxicities without affecting antitumor efficacy of immune checkpoint inhibitors.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

In the nonpivotal stage 1 of the randomized phase 3 PRESERVE-003 trial, patients with immunochemotherapy-resistant metastatic squamous non-small cell lung cancer without actionable genomic alterations treated with the next-generation, pH-sensitive anti-CTLA-4 agent gotistobart had encouraging overall survival outcomes compared to docetaxel.

Moiré superlattices are a versatile platform for studying emergent electron and quantum phenomena. Here, the authors demonstrate moiré superlattice formation in complex oxide-WS₂ heterostructures across varying twist angles.

A clinical trial testing whether monitoring ctDNA clearance during treatment for nasopharyngeal cancer could be used to inform decisions about an individual’s subsequent therapeutic programme shows promising results.

Low level of pyruvate kinase M2 (PKM2) activity in cancer cells is essential for the dependence on aerobic glycolysis. Here the authors show that PKM2 sulfhydration by hydrogen sulfide destabilizes the PKM2 tetramer, leading to reduced PKM2 enzyme activity and enhanced proliferation of breast cancer cells.

Wan, Li, Cao and colleagues report a feedback crosstalk between THY1⁺ cancer stem cells and neutrophils via migrasome-mediated release of mitochondria, which induces a pseudohypoxic state and promotes metastasis.

A testis-specific E3 ubiquitin ligase complex, ECSASB9, governs spermiogenesis by promoting TUBB4A degradation. Disruption of this pathway impairs male fertility, and pathogenic ASB9 variants are found in infertile men.

Zhang, Han, Tan, Lu, Ma et al. report that kynurenine derived from peritumoural adipose tissue is hijacked by cancer cells to mediate ferroptosis resistance, a process that could potentially be targeted with immunotherapy to inhibit tumour growth.