Intrinsic capacity, genetic susceptibility, and the risks of metabolic dysfunction-associated steatotic liver disease and cirrhosis.

Background: The World Health Organization (WHO) has introduced a new functional aging framework centered on intrinsic capacity (IC). This study aimed to evaluate the relationship between IC and the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis, and to assess the potential modifying effect of genetic susceptibility.

Methods: We included 393,355 participants without prior liver disease from the UK Biobank.

Disruption of ZC3H15 compromises telomere length maintenance by entrapping telomerase within cajal bodies.

Background: Telomere homeostasis is pivotal in various biological processes including ontogeny, reproduction, physiological aging, and the onset of numerous diseases such as tumors. In human stem cells and approximately 85% of tumor cells, telomerase formed by TERT and TERC RNA complex is responsible for elongating telomeres. However, the intricate and precise regulatory mechanisms governing telomerase remain largely elusive.

Androgen Receptor Governs Tip Cell Formation in Cerebrovascular Malformations.

Background: Cerebrovascular malformations are a pivotal cause of hemorrhage and neurological disability, orchestrated largely by aberrant vascular homeostasis. However, a malformed angiogenic regulation pattern remains elusive.

Methods: Single-cell transcriptome analysis uncovered the endothelial features of human cerebral cavernous malformations and brain arteriovenous malformations, 2 typical cerebrovascular malformation diseases.

Demarcating the Development of Cirrhosis and Its Complications via Plasma Proteomic Features in an Asymptomatic Population.

The early detection of liver cirrhosis and its complications is a conundrum in clinical practice. We aim to address this conundrum using proteomic features of plasma. A total of 52,891 participants without cirrhosis or its complications were recruited from the UK Biobank longitudinal population cohort.

Nitramine Formation via a Cryptic Non-Ribosomal Peptide Synthetase-Dependent Strategy in N-Nitroglycine Biosynthesis.

N-nitroglycine (NNG), a rare nitramine natural compound, is the only known example produced by streptomyces strains. In this study, we clarified that NNG biosynthesis originates from glycine and l-lysine and elucidated its biosynthetic gene cluster (BGC) nng. This cluster shares high homology with the recently reported BGCs of diazo compound azaserine.

DNA Metabarcoding Illuminates Seasonal Dietary Pattern and Niche Partitioning by Three Sympatric Herbivores.

Diet composition is among the most critical dimensions of animal ecology, yet seasonal dietary diversity has rarely been investigated in sympatric herbivores. This study used DNA metabarcoding to conduct an analysis of seasonal variations in diet composition and trophic niches for sympatric sika deer, Reeves' muntjac, and Chinese hare in Taohongling National Nature Reserve (TNNR). The results showed that (11.

Local DIO2 Elevation Is an Adaption in Malformed Cerebrovasculature.

Background: Cerebrovascular malformations are a pivotal cause of hemorrhage and neurological disability alongside lacking effective medication. Thyroid hormones (THs), including thyroxine and triiodothyronine, are essential for vascular development, yet whether they participate in malformed cerebrovascular pathology remains elusive.

Methods: Single-cell transcriptome analysis characterized human cerebral cavernous malformations and brain arteriovenous malformations, 2 typical cerebrovascular malformation diseases.

DNA metabarcoding reveals diet diversity and niche partitioning by two sympatric herbivores in summer.

Background: Food provides essential nutrients and energy necessary for animals to sustain life activities. Accordingly, dietary niche analysis facilitates the exploration of foraging strategies and interspecific relationships among wildlife. The vegetation succession has reduced understory forage resources (.

HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance.

Biomolecular condensates, such as the nucleolus, stress granules/processing bodies and germ granules, are multiphase assemblages whose formation mechanisms and significance remain poorly understood. Here we identify protein constituents of the spatiotemporally ordered P, Z and M multiphase condensates in Caenorhabditis elegans germ granules using optimized TurboID-mediated proximity biotin labelling. These include 462, 41 and 86 proteins localizing to P, Z and M condensates, respectively, of which 522 were previously unknown protein constituents.

Impact of steel slag, gypsum, and coal gangue on microbial immobilization of metal(loid)s in non-ferrous mine waste dumps.

Non-ferrous mine waste dumps globally generate soil pollution characterized by low pH and high metal(loid)s content. In this study, the steel slag (SS), gypsum (G), and coal gangue (CG) combined with functional bacteria consortium (FB23) were used for immobilizing metal(loid)s in the soil. The result shown that FB23 can effectively decrease As, Pb, and Zn concentrations within 10 d in an aqueous medium experiment.

Bioindicator responses to extreme conditions: Insights into pH and bioavailable metals under acidic metal environments.

Acid mine drainage (AMD) caused environmental risks from heavy metal pollution, requiring treatment methods such as chemical precipitation and biological treatment. Monitoring and adapting treatment processes was crucial for success, but cost-effective pollution monitoring methods were lacking. Using bioindicators measured through 16S rRNA was a promising method to assess environmental pollution.

The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb.

Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID.

Liver ACSM3 deficiency mediates metabolic syndrome via a lauric acid-HNF4α-p38 MAPK axis.

Metabolic syndrome combines major risk factors for cardiovascular disease, making deeper insight into its pathogenesis important. We here explore the mechanistic basis of metabolic syndrome by recruiting an essential patient cohort and performing extensive gene expression profiling. The mitochondrial fatty acid metabolism enzyme acyl-CoA synthetase medium-chain family member 3 (ACSM3) was identified to be significantly lower expressed in the peripheral blood of metabolic syndrome patients.

Unraveling assemblage of microbial community dwelling in Dabaoshan As/Pb/Zn mine-impacted area: A typical mountain mining area of South China.

Microbial community assemblage includes microorganisms from the three domains including Bacteria, Archaea, and Eukarya (Fungi), which play a crucial role in geochemical cycles of metal(loid)s in mine tailings. Mine tailings harbor vast proportions of metal(loid)s, representing a unique source of co-contamination of metal(loid)s that threaten the environment. The elucidation of the assembly patterns of microbial communities in mining-impacted ecospheres has received little attention.

ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.

Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway.

GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals.

Arteriovenous malformations (AVMs) are fast-flow vascular malformations and refer to important causes of intracerebral haemorrhage in young adults. Getting deep insight into the genetic pathogenesis of AVMs is necessary. Herein, we identified two vital missense variants of G protein-coupled receptor (GPCR) associated sorting protein 1 (GPRASP1) in AVM patients for the first time and congruously determined to be loss-of-function variants in endothelial cells.

Ilexchinene, a new seco-ursane triterpenoid from the leaves of Ilex chinensis with therapeutic effect on neuroinflammation by attenuating the MAPK/NF-κB signaling pathway.

Background: Neuroinflammation is a vital factor participating in the whole pathogenetic process of diverse neurodegenerative disorders, but accessible clinical drugs are still insufficient due to their inefficacy and side effects. Triterpenoids are reported to possess potential anti-neuroinflammatory activities, and the leaves of Ilex chinensis are a commonly used herbal medicine containing many ursane-type and oleanane-type triterpenoids. However, the novel triterpenoids from I.

Microbial metabolic activity in metal(loid)s contaminated sites impacted by different non-ferrous metal activities.

Many non-ferrous metal mining and smelting activities have caused severe metal(loid) contamination in the local soil environment. The metabolic activity of soil microorganisms in four areas affected by different metallurgical activities (production vs. waste disposal) was characterized using a contamination gradient from the contaminated site to the surrounding soils.

Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery.

Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases, including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory processes remain poorly defined. Through a genome-wide synthetic viability screen for PARP-inhibitor resistance using an inducible CRISPR-Cas9 platform and BRCA1-deficient breast cancer cells, we identified a transmembrane nuclease (renamed NUMEN) that could facilitate compartmentalized and non-homologous end joining-dependent repair of double-stranded DNA breaks at the nuclear periphery.

mTORC1-Induced Bone Marrow-Derived Mesenchymal Stem Cell Exhaustion Contributes to the Bone Abnormalities in -Deficient Mice of Premature Aging.

Stem cell exhaustion is a hallmark of aging. -deficient mice ( mice) is a murine model that mimics human aging with significant bone abnormalities. The aim of this study is using mice to investigate the functional change of bone marrow-derived mesenchymal stem cells (BMSCs) and explore the underlying mechanism.

Single-cell sequencing reveals that endothelial cells, EndMT cells and mural cells contribute to the pathogenesis of cavernous malformations.

Cavernous malformations (CMs) invading the central nervous system occur in ~0.16-0.4% of the general population, often resulting in hemorrhages and focal neurological deficits.

An inducible CRISPR/Cas9 screen identifies DTX2 as a transcriptional regulator of human telomerase.

Most tumor cells reactivate telomerase to ensure unlimited proliferation, whereas the expression of human telomerase reverse transcriptase () is tightly regulated and rate-limiting for telomerase activity maintenance. Several general transcription factors (TFs) have been found in regulating transcription; however, a systematic study is lacking. Here we performed an inducible CRISPR/Cas9 KO screen using an core promoter-driven reporter.