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Preliminary results from an investigator-initiated clinical trial showed that an AAV-OTOF gene therapy was safe and led to hearing improvements in ten patients with congenital deafness with 6–12 months of follow-up, including in a teenager and a young adult, expanding the age range from previous trials.

Maintaining proper reactive oxygen species (ROS) balance is critical for cellular and individual health, yet its dynamic nature encumbers monitoring and assessment. Here the authors propose a platform using mass cytometry-based detection, termed SN-ROP, to identify distinct ROS profiles associated with specific immune cell functions and disease states.

Passive immunisation for respiratory syncytial virus for infants is recommended by the World Health Organization but products currently available have limited duration of protection. Here, the authors investigate the age distribution of infant hospitalisation for respiratory syncytial virus to inform optimal timing of immunisation.

Epstein-Barr virus is associated with increased cancer risk. Here, the authors analysed two population-based prospective cohorts in Southern China to examine the association between increased seropositivity and the risk of multiple cancer types.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

The Einstein Probe has discovered a fast X-ray transient, EP240414a, associated with a broad-lined type Ic supernova. Its unusually soft spectrum and weak jet add to the diversity of stellar deaths and suggest a previously unknown Wolf–Rayet star explosion mechanism.

In a reverse-translational study followed by a clinical trial, the targeting of antigen-presenting mast cells was identified as a therapeutic approach to overcome anti-PD-1 resistance in patients with metastatic triple-negative breast cancer who experienced clinical benefit when treated with the mast cell stabilizer cromolyn.

Cancer stem cells (CSCs) are thought to be the main drivers for disease progression and treatment resistance in liver cancer. This study identifies the LGR5+ compartment as an important CSC population, representing a viable therapeutic target for combating liver cancer.

Sun, Fu, Zheng, Hong, Liu et al. generate a single-nucleus transcriptomic atlas of the primate cochlear aging, identifying an age-related decline in Slc35f1 and showing that silencing Slc35f1 in mice induces hair cell degeneration and auditory deficits.

Genome and transcriptome analyses of 376 Gossypium hirsutum accessions uncover the regulation of gene expression during fiber development in allotetraploid cotton and highlight the potential for fiber quality improvement.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration.

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.

Integrated structural and technological changes across the Chinese pork supply chain can improve production and meet demand while reducing phosphorous and nitrogen losses.

Many drugs discovered by serendipity possess the ability to react with cysteine residues on target proteins. Here the authors report a large-scale chemoproteomic analysis to define proteome-wide ligandability maps of 70 drugs with diverse cysteine-reactive chemotypes in native biological systems.

The efficient preparation of inherently unstable N-CF3 secondary amines remains a challenge in synthetic chemistry. Herein, the authors present the synthesis of this type of compounds via oxidative fluorination of isocyanides using iodine as the oxidant, silver fluoride as the fluorinating reagent, and tert-butyldimethylsilane as the proton precursor.

As a major source of reactive oxygen species, mitochondria face a challenge to maintain their redox state. Here the authors show that ROMO1 overexpression prevents deleterious oxidation of the mitochondrial cysteinome and exerts beneficial effects on mitochondrial function.

Prostate cancer is heterogenous in response to therapy. Here, the authors analyse genomics, transcriptomics, proteomics and phosphoproteomics data from 145 prostate cancer patients to identify NANS as a therapeutic target in prostate cancer.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

‘Gastric cancer metastasis to the ovary is difficult to treat and is not fully understood. Here, the authors characterized mutations in a cohort of matched primary and metastatic disease, and found mutations, including in CLDN18, could predict treatment response to paclitaxel.

Using bulk heart transcriptomics of rat models of right and left ventricle failure, Jurida et al. examined transcriptional changes in cardiomyocytes during the progression of heart failure and the overlap with transcriptomics from humans with chronic thromboembolic pulmonary hypertension (CTEPH), identifying more than 50 genes whose expression levels correlate with the severity of right heart disease.

Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. Herein, the authors present a simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization.

Aging is the risk factor for chronic pancreatitis and its acute attack. Here, the authors show that exocrine acinar cells received endocrine β-cell-derived miR-503-322 and caused pancreas autodigestion and anti-proliferation by repressing MKNK1 thereby promoting pancreatitis in the elderly

Breviscapine is the flavonoid extract from medical plant Erigeron breviscapus for the treatment of cardio- and cerebrovascular disease. Here, the authors identify the key enzymes of the biosynthetic pathway from the plant genome and engineer yeast to produce breviscapine from glucose.

Worldwide, the number of only-child families is increasing. This research examines how growing up without siblings affects adult brain structure, function and connectivity, cognition, personality and mental health.

The molecular mechanisms underlying metabolic remodelling in colorectal cancer (CRC) are not completely elucidated. Here, they authors show that the oncogenic protein MYG1 promotes CRC progression not only through regulating mitochondrial activity, but also through activating a nuclear-associated pathway for glycolysis increase.

This study demonstrated that different types of HC-Pros from potyviruses exhibit varying capacities to inhibit HEN1. This results in distinct levels of autophagic AGO1 degradation, which in turn leads to differences in RNA silencing suppression efficiency.

The compassionate use of l-asparaginase in patients suffering from nasopharyngeal carcinoma substantially strengthens the efficacy of immune-checkpoint blockade therapy by enhancing T cell fitness.

Multimodal large language models (MLLMs) hold promise for a range of medical applications. Here, the authors use MLLMs for 3D brain CT radiology report generation, demonstrating that combining anatomy-aware model fine-tuning with robust evaluation metrics establishes a comprehensive and effective framework.

Socioeconomic status is multidimensional and can change over time. Xu, Lui, Ji et al. found dimension-specific, late-stage-specific and change-specific socioeconomic effects on brain, cognition, personality and emotion.

Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Here, the authors develop an automated OAR segmentation system to delineate a comprehensive set of 42 H&N OARs.

Effectively delivering medications to the renal tubule to delay or halt chronic kidney disease progression remains a significant unmet clinical challenge. Here, authors introduce an innovative strategy for renal tubule targeting using biomimetic high-density lipoprotein (bHDL) nanoparticles.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The authors report Bose–Einstein condensation of a two-magnon bound state in Na₂BaNi(PO₄)₂. This should stimulate further work on these types of geometrically frustrated materials.

Studying tumour heterogeneity and tumour evolution remains a challenging task. Here, the authors propose a supercontinuum-tailoring two-photon microscope to enable the imaging of multiple fluorophores with a single light beam. They use this tool to monitor the dynamics of heterogeneous tumour evolution.

The photocatalytic reforming of plastics into value-added chemicals offers a promising strategy to address environmental challenges while providing significant energy benefits. Here, the authors develop modified carbon nitride with enhanced visible light absorption, effectively anchoring under-coordinated IrN₂O₂ sites to catalyze the oxidation of persistent plastic derivatives.

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.

Vacuolar sugar transporters have a key role in plant sugar homeostasis. This Review discusses recent advances concerning the interconnected roles of vacuolar sugar transporters from different protein families in plant development and stress responses.

In a phase 1 trial, pediatric or adult patients with T-ALL who received CD5-targeted CAR-T cell therapy using cells from previous or newly matched donors showed an encouraging clinical response rate, with some severe adverse events that required attention and effective management.

COVID-19-related non-pharmaceutical interventions impacted the circulation of other pathogens. Here, the authors compile a global viral activity dataset and compare the timing of resurgence of seven common respiratory viruses following the relaxation of interventions across different geographical regions.