Browse Articles

Efficient and accurate neural-field reconstruction using resistive memory

Two-component exciton condensates in an electron–hole bilayer

Giant crustacean of the deep sea steals a trick from bacteria

Lignin to adipic acid in a high-yield chemical and biological redox process

Chinese detector edges closer to solving the mystery of neutrino mass

Human migration has surged since 2000 — these maps reveal where people are going

Translation-dependent degradation of cas12 mRNA triggered by an anti-CRISPR

People are turning to AI chatbots to plug gaps in health information

Seven steps for critically analysing research papers

Vaccination generates broadly cross-neutralizing antibodies to the HIV Env apex

Abstract As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans 1 . Broadly neutralizing antibodies, although rare, can be isolated from people living with HIV, revealing conserved envelope glycoprotein (Env) sites as key targets for vaccine development 2–4 . One such target is the apex of the Env spike. Here we identify a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all trimer-liposome-immunized non-human primates. Critically, we isolated monoclonal antibodies from multiple macaques that cross-neutralize divergent HIV clinical isolates. High-resolution cryogenic electron microscopy structural analyses of monoclonal antibodies from four different macaques demonstrate that they target the Env trimer apex in a manner highly similar to that of the human-infection-elicited, apex-directed broadly neutralizing antibody PG9, representing a substantial advance in HIV vaccine development.

Let’s talk about biomedical research kits

World-first: therapy to make cells young again trialled in a person

Engineering a dual-antigen mRNA vaccine to restore immune control in chronic hepatitis B

Ocean ‘cold blob’ is evidence for a troubling climate trend

Author Correction: Forecasting the dissemination of antibiotic resistance genes across bacterial genomes

A meta-analysis of infant gut viromes reveals global patterns in bacteriophage community assembly and functional capacity over the first three years of life

Abstract Assembly of the gut microbiota in infancy is an important health determinant, yet the viral component, the virome, remains poorly described. Here, we conduct a meta-analysis of 12 infant cohorts across 8 countries to model gut virome development over the first three years of life. Our results revealed distinct diversity patterns, where viral richness increased significantly over the first eight months of life alongside a loss of community evenness. We define virome developmental velocity, the rate of change between sequential samples, which significantly decreased over time. This was mirrored by community-wide convergence, as infant viromes became more similar with age. Functionally, the transition to a stable state involved a significant decrease in extracellular temperate phages and shifts in phage-encoded auxiliary metabolic genes, which can modulate host metabolism. Our work provides a baseline characterization of gut virome development, marked by a conserved successional trajectory, providing a framework to identify disease-associated perturbations.

Targeting the METTL1/m7G axis as a therapeutic strategy in myeloid leukemia

Abstract N7-methylguanosine (m7G), a prevalent modification in transfer RNAs (tRNAs), is primarily catalyzed by the methyltransferase METTL1. Although growing evidence supports a role for METTL1 in various tumors, its therapeutic potential and precise function in leukemia stem cell (LSC) homeostasis remain largely unexplored. Here, we identify METTL1 as a key regulator of LSC self-renewal and homing within bone marrow (BM) microenvironment through catalyzing m7G formation on a specific tRNA, tRNAPheGAA, thereby promoting leukemogenesis. Mechanistically, METTL1 loss significantly reduces m7G abundance and steady-state levels of tRNAPheGAA, leading to translation suppression and degradation of transcripts enriched with tRNAPheGAA-related codons, such as hematopoietic cell kinase (HCK). Decreased HCK expression disrupts CXCR4 signaling, impairing LSC self-renewal and BM homing. Therapeutically, we characterized a small-molecule METTL1 inhibitor (M1i; NSC137443), through high-throughput screening. Pharmacological inhibition of METTL1 demonstrated potent antitumor efficacy by reducing tRNA m7G levels and disrupting the tRNAPheGAA/HCK/CXCR4 cascade. Notably, targeting METTL1 significantly reduces LSC frequency, delays leukemogenesis, and prolongs survival in multiple acute myeloid leukemia models. Together, our findings establish a previously unrecognized role for METTL1 and its target tRNAPheGAA in LSC homeostasis and provide compelling proof-of-concept evidence that METTL1 is a druggable epitranscriptomic target for antileukemia therapy.

Early neonatal mortality and its associated factors at Doctor Bogalech Gebre Memorial General Hospital, Central Ethiopia: A cross-sectional study

Attaining 19.12% solar cell efficiency for non-fused ring electron acceptors via multi-dimensional charge transport

Venetoclax combinations in untreated CLL: 5-year results and patient-reported outcomes analysis of the CLL13/GAIA trial

Abstract Fixed-duration venetoclax combinations have become a standard first-line treatment in chronic lymphocytic leukemia (CLL). The phase 3 CLL13/GAIA trial assesses 3 time-limited combinations: venetoclax-rituximab (RV), venetoclax-obinutuzumab (GV), and venetoclax-obinutuzumab-ibrutinib (GIV), in comparison with chemoimmunotherapy (CIT). Fit patients with CLL without TP53 aberrations were randomized between 6 cycles of CIT (fludarabine-cyclophosphamide-rituximab [FCR] or bendamustine-rituximab [BR]) or 12 cycles of RV, GV, or GIV (GIV: ibrutinib continuation until cycle 36 if measurable residual disease at months 12/15). In total, 926 patients were randomized (GIV: 231, GV: 229, RV: 237, and CIT: 229 [FCR: 150, BR: 79]). With a median observation time of 63.8 months, 5-year progression-free survival (PFS) rates were 81.3% (GIV), 69.8% (GV), 57.4% (RV), and 50.7% (CIT). PFS was superior for GV and GIV compared with CIT and RV (P< .001 in each case). In addition, GIV showed longer PFS than GV (P = .0046). Venetoclax-based re-treatment after venetoclax-based first-line regimens was efficacious, with 2-year treatment-free survival >80% from second-line treatment. No differences in overall survival were observed between treatment arms (5-year rates: GIV, 94.3%; GV, 93.6%; RV, 94.7%; and CIT, 90.7%). The incidence rates of severe infections were highest with CIT, whereas cardiac events were most frequent with GIV. Compared with patients treated with CIT, those treated with GV or RV reported rapid and significantly greater quality-of-life (QoL) improvements. In the GIV arm, clinically relevant QoL improvements occurred later (month 15, after the end of treatment in most patients) than with GV/RV, likely due to a higher treatment-related symptom burden. This trial was registered at www.clinicaltrials.gov as NCT02950051.