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Here, the authors develop AMPLiT a tool for screening antimicrobial peptides in metagenomic datasets, and apply it to human coprolite metagenomes, finding that Segatella copri, an ancient prevalent human gut bacterium declined in modern populations, harbors unexplored antimicrobial reservoir, offering an alternative approach against modern pathogenic infections.

Here, the authors identify distinct, autism-specific diet microbiome interactions, showing how unhealthy diets and synthetic emulsifiers drive dysbiosis. The findings pave the way for microbiome-aware dietary strategies for autism.

Semaglutide, a GLP-1 receptor agonist, may offer neuroprotective benefits after stroke, but its effects in large vessel occlusion (LVO) are unknown. Here the authors show, in a phase 2 randomized trial, that semaglutide is safe after endovascular therapy and may improve recovery in patients not receiving intravenous thrombolysis.

Based on two waves of data collection from 748 households in Hong Kong, this analysis sheds light on the number of transmission events that occurred before manifestation of symptoms in influenza A and B cases.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

While antivirals like nirmatrelvir/ritonavir and molnupiravir are known to reduce severe COVID-19, their impact on cardiovascular outcomes is unclear. Here, the authors use a target trial emulation design to show that nirmatrelvir/ritonavir significantly lowers long-term cardiovascular risks among hospitalized patients, highlighting its potentials over molnupiravir for mitigating post-COVID-19 cardiovascular complications.

Myotonic dystrophy type 1 affects both muscle and neuronal function, but its synaptic pathology is poorly understood. Here, the authors show that upregulation of FasII (NCAM1) in both pre- and postsynaptic cells synergistically drives neuropathological and behavioral DM1 phenotypes, which can be rescued by FasII knockdown or specific isoform modulation.

KP.3.1.1 S S31del confers enhanced immune escape and increased infectivity, which is counterbalanced by NSP10 S33C. The opposing effects of these mutations highlight the complex interplay of viral genomic elements in shaping their overall fitness.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

METTL3 promotes healthy placenta function by regulating m⁶A methylation and histone epigenetics. Deficiency in METTL3 leads to premature senescence, inflammation activation of trophoblasts, contributing to pregnancy complications like preeclampsia.

Increasing evidence suggests that activation of oncogenic pathways contributes to an unfavorable tumor microenvironment. Here, the authors show that wild-type KRAS plays a key role in immune evasion in hepatocellular carcinoma by impairing interferon-mediated immunity and promoting resistance to immunotherapy via the EGFR/MEK/ERK pathway.

Extending the interval between doses of mRNA Covid-19 vaccines has been linked with a reduced risk of myocarditis in children and adolescents, but impacts on vaccine effectiveness are not known. Here, the authors perform a nested case-control study using data from Hong Kong and find evidence of reduced risk of infection following a longer dosing interval.

In a large multinational cohort study, maternal, gestational or pregestational diabetes was associated with only a small-to-moderate risk of ADHD in offspring, contrary to previous estimates that showed stronger effect sizes, attributing the differences in findings to confounding by shared genetic and familial factors.

DNA methylation and copy number variant analyses across a large number of genetic mouse models of pediatric brain tumors reveal subtype-specific molecular alterations shared with the corresponding human diseases.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

There is evidence of increased risk of myasthenia gravis following statin therapy. Here the authors investigated this association using electronic health records and suggest a minimum monitoring period of approximately six months for MG symptoms for patients starting using statins.

Authors present a bispecific antiviral design targeting the virus and the host that simultaneously offers broad-spectrum protection against multiple existing transmissible human-pathogenic coronaviruses, including the Paxlovid-resistant SARS-CoV-2 mutants.

A model that predicts the effectiveness of COVID-19 vaccines against circulating SARS-CoV-2 variants, before the acquisition of real-world effectiveness data, may help guide more rapid public health and research responses to new variants of concern.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

SARS-CoV-2 variants of concern such as the Omicron variant pose a challenge for vaccination and antibody immunotherapy. Here, Zhou et al. isolate a broadly neutralizing antibody (bNAb), named ZCB11, that protects Golden Syrian hamsters against Omicron. Applying CryoEM the authors show that ZCB11 heavy chain predominantly interacts with RBD in up confirmation, which interferes with ACE2 receptor binding.

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Seasonal influenza vaccine effectiveness depends on including virus strains in the vaccine that closely match those circulating in the upcoming season. In this study, the authors develop a computational model of influenza virus evolution to predict future circulating strains and therefore support vaccine strain selection.

Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.

Although extrapulmonary complications of different organ systems are recognized in patients with severe COVID19 effects are less well studied. Here, Qiao et al. characterize the pathogenesis of SARS-CoV-2 on bone metabolism in Syrian hamster and find that bone loss is associated with virus-mediated cytokine dysregulation.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Hong Kong experienced a severe wave of SARS-CoV-2 in early 2022. Here, the authors use genomic and serosurveillance data and show that this wave was dominated by the Omicron BA.2 sublineage, and that low protective immunity, particularly in older age groups, contributed to its severity.

Here, the authors show that a single mutation in JN.1 spike, L455S, confers better spike cleavage and enhances virus infectivity in differentiated primary human nasal epithelial cells while increasing immune evasiveness, contributing to the efficient spread of JN.1.

Endothelin-1 activation after SARS-CoV-2 infection leads to vascular permeability, chondrocyte senescence, osteoclast activation and cyst formation in affected joints of hamsters, which can be alleviated using macitentan. Joint injury was also seen in two patients after COVID-19 infection.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Nasopharyngeal cancer is frequently characterized by Epstein-Barr virus infection. Here, using genomic analyses, the authors find that the tumours harbour mutations in genes involved in the NF-κB signalling pathway or overexpress a viral oncoprotein, latent membrane protein 1.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

SARS-CoV-2 rebound is a recurrence of symptoms or return to test positivity after initial recovery. Here, the authors demonstrate an association between SARS-CoV-2 rebound and post-acute COVID conditions using data from Hong Kong.

Coronaviruses exploit the host caspase-6 to cleave coronavirus nucleocapsid protein into fragments with interferon-antagonizing activity to facilitate virus replication.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Difficulties in propagating HRV-C have hindered our understanding of this common respiratory pathogen. Here, authors developed an organoid-based system to reproducibly propagate HRV-C and characterized HRV-C infection in physiologically active respiratory organoids.