Regulatory Genomic Circuitry of Brain Age by Integrative Functional Genomic Analyses.

Brain age gap (BAG) is a valuable biomarker for evaluating brain healthy status and detecting age-associated cognitive degeneration. However, the genetic architecture of BAG and the underlying mechanisms are poorly understood. Here, we estimated brain age from magnetic resonance imaging with improved accuracy using our proposed adversarial convolution network (ACN), followed by applying the ACN model to an elder cohort from UK Biobank.

Sensitive Detection of Vitamin B2 in a Microdroplet with a Living Graphene Hydrogel Needle.

As a water-soluble vitamin, Vitamin B2 (VB2) is crucial for the health of living organisms. Therefore, developing sensitive and selective methods for detecting VB2 is essential for the quality control of food and pharmaceuticals as well as for clinical diagnosis. In this study, a cell-embedded living graphene hydrogel needle was prepared under ambient atmospheric conditions, where the electroactive bacteria MR-1 was used to induce the reduction of graphene oxide (GO) to graphene hydrogel under the confinement effect with a glass capillary tube.

Biases and complementarity in gut viromes obtained from bulk and virus-like particle-enriched metagenomic sequencing.

Unlabelled: Due to varying sequencing strategies, current gut virome findings show significant variability. Specifically, bulk- and virus-like particle (VLP)-enriched metagenomic sequencing (termed bulk and VLP, respectively) present unique advantages and limitations, affecting viral genome discovery, taxonomic annotation, and community structure analysis. A comprehensive comparison of these strategies is crucial for thoroughly understanding the gut virome.

Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a decade-long preclinical pathological period that can be divided into several stages. Emerging evidence has revealed that the microbiota-gut-brain axis plays an important role in AD pathology. However, the role of gut microbiota in different AD stages has not been well characterized.

Spatiotemporally resolved transcriptomics reveals the cellular dynamics of human retinal development.

The morphogenesis and cellular interactions in developing retina are incompletely characterized. The full understanding needs a precise mapping of the gene expression with a single-cell spatial resolution. Here, we present a spatial transcriptomic (ST) resource for the developing human retina at six developmental stages.

Integrating rare pathogenic variant prioritization with gene-based association analysis to identify novel genes and relevant multimodal traits for Alzheimer's disease.

Introduction: Increasing evidence has highlighted rare variants in Alzheimer's disease (AD). However, insufficient sample sizes, especially in underrepresented ethnic groups, hinder their investigation. Additionally, their impact on endophenotypes remains largely unexplored.

Complementary insights into gut viral genomes: a comparative benchmark of short- and long-read metagenomes using diverse assemblers and binners.

Background: Metagenome-assembled viral genomes have significantly advanced the discovery and characterization of the human gut virome. However, we lack a comparative assessment of assembly tools on the efficacy of viral genome identification, particularly across next-generation sequencing (NGS) and third-generation sequencing (TGS) data.

Results: We evaluated the efficiency of NGS, TGS, and hybrid assemblers for viral genome discovery using 95 viral-like particle (VLP)-enriched fecal samples sequenced on both Illumina and PacBio platforms.

Plasma proteomics identifies proteins and pathways associated with incident depression in 46,165 adults.

Proteomic alterations preceding the onset of depression offer valuable insights into its development and potential interventions. Leveraging data from 46,165 UK Biobank participants and 2920 plasma proteins profiled at baseline, we conducted a longitudinal analysis with a median follow-up of 14.5 years to explore the relationship between plasma proteins and incident depression.

Association of birth weight with neuropsychological functioning in early adolescence: A retrospective cohort study.

Objective: This study aimed to compare the neuropsychological function in early adolescence between children born small for gestational age (SGA) or large for gestational age (LGA) and those born appropriate for gestational age (AGA).

Methods: This retrospective cohort study utilized data from the Adolescent Brain Cognitive Development study in 2016-18. Children born of singleton pregnancy with complete information of birth weight and delivery week were enrolled.

Energy Landscape Reveals the Underlying Mechanism of Cancer-Adipose Conversion in Gene Network Models.

Cancer is a systemic heterogeneous disease involving complex molecular networks. Tumor formation involves an epithelial-mesenchymal transition (EMT), which promotes both metastasis and plasticity of cancer cells. Recent experiments have proposed that cancer cells can be transformed into adipocytes via a combination of drugs.

A catalog of small proteins from the global microbiome.

Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we construct a global microbial smORFs catalog (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes.

Individual cell modification with cell surface specific atom transfer radical polymerization for enhanced Cr(VI) removal.

Modifying cells with polymers on the surface can enable them to gain or enhance function with various applications, wherein the atom transfer radical polymerization (ATRP) has garnered significant potential due to its biocompatibility. However, specifically initiating ATRP from the cell surface for in-situ modification remains challenging. This study established a bacterial surface-initiated ATRP method and further applied it for enhanced Cr(VI) removal.

Long-read sequencing reveals extensive gut phageome structural variations driven by genetic exchange with bacterial hosts.

Genetic variations are instrumental for unraveling phage evolution and deciphering their functional implications. Here, we explore the underlying fine-scale genetic variations in the gut phageome, especially structural variations (SVs). By using virome-enriched long-read metagenomic sequencing across 91 individuals, we identified a total of 14,438 nonredundant phage SVs and revealed their prevalence within the human gut phageome.

Association between twin status with cognitive, behavioral development and brain structure in early adolescence: a retrospective cohort analysis based on the Adolescent Brain Cognitive Development Study.

Twin births are related with maternal and fetal adverse outcomes. Little was known about the comparability of the cognitive, behavioral development and brain structure between twins and singletons in early adolescence. This retrospective cohort study was based on data from the United States population-based, prospective, longitudinal observational Adolescent Brain Cognitive Development study.

VirRep: a hybrid language representation learning framework for identifying viruses from human gut metagenomes.

Identifying viruses from metagenomes is a common step to explore the virus composition in the human gut. Here, we introduce VirRep, a hybrid language representation learning framework, for identifying viruses from human gut metagenomes. VirRep combines a context-aware encoder and an evolution-aware encoder to improve sequence representation by incorporating k-mer patterns and sequence homologies.

Discovery of antimicrobial peptides in the global microbiome with machine learning.

Novel antibiotics are urgently needed to combat the antibiotic-resistance crisis. We present a machine-learning-based approach to predict antimicrobial peptides (AMPs) within the global microbiome and leverage a vast dataset of 63,410 metagenomes and 87,920 prokaryotic genomes from environmental and host-associated habitats to create the AMPSphere, a comprehensive catalog comprising 863,498 non-redundant peptides, few of which match existing databases. AMPSphere provides insights into the evolutionary origins of peptides, including by duplication or gene truncation of longer sequences, and we observed that AMP production varies by habitat.

Unnatural Direct Interspecies Electron Transfer Enabled by Living Cell-Cell Click Chemistry.

Direct interspecies electron transfer (DIET) is essential for maintaining the function and stability of anaerobic microbial consortia. However, only limited natural DIET modes have been identified and DIET engineering remains highly challenging. In this study, an unnatural DIET between Shewanella oneidensis MR-1 (SO, electron donating partner) and Rhodopseudomonas palustris (RP, electron accepting partner) was artificially established by a facile living cell-cell click chemistry strategy.

An augmented Mendelian randomization approach provides causality of brain imaging features on complex traits in a single biobank-scale dataset.

Mendelian randomization (MR) is an effective approach for revealing causal risk factors that underpin complex traits and diseases. While MR has been more widely applied under two-sample settings, it is more promising to be used in one single large cohort given the rise of biobank-scale datasets that simultaneously contain genotype data, brain imaging data, and matched complex traits from the same individual. However, most existing multivariable MR methods have been developed for two-sample setting or a small number of exposures.

Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial.

Objective: We aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.

Design: Healthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing.

STAB2: an updated spatio-temporal cell atlas of the human and mouse brain.

The brain is constituted of heterogeneous types of neuronal and non-neuronal cells, which are organized into distinct anatomical regions, and show precise regulation of gene expression during development, aging and function. In the current database release, STAB2 provides a systematic cellular map of the human and mouse brain by integrating recently published large-scale single-cell and single-nucleus RNA-sequencing datasets from diverse regions and across lifespan. We applied a hierarchical strategy of unsupervised clustering on the integrated single-cell transcriptomic datasets to precisely annotate the cell types and subtypes in the human and mouse brain.

Engineering of cytosine base editors with DNA damage minimization and editing scope diversification.

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells.

Computational exploration of the global microbiome for antibiotic discovery.

Novel antibiotics are urgently needed to combat the antibiotic-resistance crisis. We present a machine learning-based approach to predict prokaryotic antimicrobial peptides (AMPs) by leveraging a vast dataset of 63,410 metagenomes and 87,920 microbial genomes. This led to the creation of AMPSphere, a comprehensive catalog comprising 863,498 non-redundant peptides, the majority of which were previously unknown.

Common and disorder-specific cortical thickness alterations in internalizing, externalizing and thought disorders during early adolescence: an Adolescent Brain and Cognitive Development study.

Background: A growing body of neuroimaging studies has reported common neural abnormalities among mental disorders in adults. However, it is unclear whether the distinct disorder-specific mechanisms operate during adolescence despite the overlap among disorders.

Methods: We studied a large cohort of more than 11 000 preadolescent (age 9-10 yr) children from the Adolescent Brain and Cognitive Development cohort.