Identification of key genes associated with butyrate metabolism in keratoconus through Mendelian randomization and transcriptomic analysis.

Hidden diversity of marine zooplankton under sea ice in the Okhotsk Sea: Insights from community and population analyses based on DNA metabarcoding.

R-loop-driven molecular subtypes reveal prognostic and immunogenomic features in uterine corpus endometrial carcinoma.

This study aimed to make a direct comparison of four tumor burden-related prognostic systems in predicting prognoses in patients with colorectal liver metastasis (CRLM) undergoing hepatectomy. Clinicopathological and survival data of 197 consecutive CRLM patients were extracted from a public database. Clinical Risk Score-derived N1S5 (lesion number of 1 and the largest size of 5cm are cutoffs for risk stratification), tumor burden score (TBS), modified TBS (mTBS) and total tumor volume (TTV) were calculated, and patients were stratified to different risk groups. Kaplan-Meier plots were adopted to depict the survival probabilities. Cox regression analyses were performed to evaluate the association between these systems and overall survival (OS) and disease-free survival (DFS). N1S5 and TTV systems effectively stratified patients into distinct risk groups with significantly different OS and DFS (p<0.05), but TBS and mTBS did not. Multivariable Cox regression analysis demonstrated N1S5 and TTV as independent variables associated with OS (HRs: 1.43 to 1.97, 1.59 to 1.76, respectively) and DFS (HRs: 1.34 to 2.09, and 1.80 to 2.51, respectively) (p<0.05). Compared with the other three systems, TTV showed a relatively higher time-dependent area under the curve (median: 0.60) and C-index (median: 0.64) for predicting OS. N1S5 had the highest C-index (median: 0.63) for predicting DFS. Total tumor volume seems to be a robust and effective tool for risk stratification and prognosis prediction in CRLM patients undergoing liver resection. N1S5 may provide a pragmatic simplified alternative to total tumor volume for prognostic prediction.

Computationally predicting protein-protein interactions (PPIs) is challenging due to the lack of integrated, multimodal protein representations. DeepDrug Protein Embeddings Bank (DPEB) is a curated collection of 22 043 human proteins that integrates four embedding types: structural (AlphaFold2), transformer-based sequence (BioEmbeddings), contextual amino acid patterns (ESM-2: Evolutionary Scale Modeling), and sequence-based n-gram statistics (ProtVec). AlphaFold2 protein structures are available through public databases (e.g. AlphaFold2 Protein Structure Database), but the internal neural network embeddings are not. DPEB addresses this gap by providing AlphaFold2-derived embeddings for computational modeling. Our benchmark evaluations show GraphSAGE with BioEmbedding achieved the highest PPI prediction performance (87.37% AUROC, 79.16% accuracy). The framework also achieved 77.42% accuracy for enzyme classification and 86.04% accuracy for protein family classification. DPEB supports multiple graph neural network methods for PPI prediction, enabling applications in systems biology, drug target identification, pathway analysis, and disease mechanism studies.

JOURNAL/nrgr/04.03/01300535-202606000-00081/figure1/v/2026-02-11T151048Z/r/image-tiff To perform various functions in the body, skeletal muscle is controlled and coordinated as a whole by nerves. However, there has been little research into whether the nerve control characteristics of different muscles are different, and the importance of these potential differences. In the present study, we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles. We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways. In terms of spatial distribution patterns, sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons. In addition, the neuronal innervation of limb muscles exhibited four different characteristics: sympathetic neuron-rich muscle, sensory neuron-rich muscle, neuron-sparse muscle, and motor neuron-rich muscle. Sensory neuron density was mainly associated with muscle contractile structure and cell pH, whereas sympathetic neuron density was associated with protein kinase activity, muscle vasculature, muscle calcium-dependent protein kinase activity, lipid transport, and vesicle release. Motor neuron density was mainly associated with protein kinase activity, cell adhesion, oxidoreductase activity, and exocytosis. These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions, thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.

Cisplatin (DDP) is a key chemotherapeutic agent for pancreatic cancer (PC), but its efficacy is often limited by the development of DNA damage repair (DDR)-mediated resistance. Ubiquitin-specific peptidase 15 (USP15) is known to activate DDR pathways; however, its specific role and clinical relevance in PC remain poorly understood. We analyzed USP15 expression and its clinical significance using public databases, tissue microarrays, and cell lines through RT-qPCR, Western blot, and immunohistochemistry. The effect of USP15 on DDP resistance was evaluated using colony formation and flow cytometry assays. Protein interaction between USP15 and POLE3 was confirmed by Co-IP. DNA damage levels were assessed via immunofluorescence staining, neutral comet assays, and host cell reactivation. Both loss-of-function and gain-of-function studies of USP15 were conducted in a mouse xenograft model. We found that USP15 was significantly upregulated in PC tissues and correlated with poor patient prognosis. Overexpression of USP15 enhanced DDP resistance in PC cells in vitro and in vivo. Enrichment analysis indicated a strong association between USP15 expression and DDR-related genes. Mechanistically, USP15 was found to bind to POLE3 and suppress its ubiquitination-dependent degradation, thereby facilitating DDP-induced DNA damage repair. Our findings highlight the upregulation and prognostic value of USP15 in PC, and uncover its role in promoting DDR-mediated DDP resistance through stabilization of POLE3.

Ischemic stroke in Brazil (2017-2025): Trends in admissions, thrombolysis, craniectomy, costs, and COVID-19 disruption.

Significance of Methyltransferase-like 5 Expression in Oral Squamous Cell Carcinoma.

Identification and functional characterization of CXCL17 orthologs in amphibians.

Accuracy of deep learning for risk prediction and screening of diabetic foot Ulcers: A systematic review and meta-analysis.

Informal Extractivism: Mining concessions in natural protected areas in Colombia

As the population ages, there is an increasing demand for urologists who specialize in female pelvic surgery. However, 30% of residency programs lack a Urogynecology Reconstructive Pelvic Surgery (URPS)-trained attending, potentially limiting resident exposure. This study evaluated whether the presence of URPS faculty during residency would influence subsequent URPS practice patterns amongst general urologists. American Board of Urology case logs (2003-2023) were analyzed for general urologists aged ≤ 40 who graduated after 2013. Residency programs were assessed for URPS faculty presence using public databases and direct program contact. Female URPS procedures were identified by CPT codes. A total of 414 general urologists submitted 21 422 cases, including 2372 female URPS procedures. One hundred and eleven urologists without URPS attending in residency submitted 596 URPS cases (mean: 5.37 cases/urologist). Three hundred and three urologists with URPS attending in residency submitted 1776 URPS cases (mean: 5.86 cases/urologist). There was no statistical difference between the two groups in the total number of URPS procedures. Complex female URPS procedures were more likely to be performed by general urologists with URPS faculty during residency (p = 0.02). The most common procedure for both groups was sling (without URPS attending: 282/596, with URPS attending: 753/1776). General urologists who trained at a residency program that had an URPS attending on faculty were more likely to perform complex female URPS procedures. This finding underscores the potential importance and value of having an URPS attending during residency training for general urologists interested in performing more complex URPS procedures in practice.

Assessing circumstances surrounding police-related deaths is hampered by the absence of an official national database. The National Vital Statistics System, which compiles death certificates filed by medical examiners and coroners, misses approximately one-half of deaths due to police use of force. The void has been filled by the emergence of several unofficial databases sourced from public records, which have been used, for example, to estimate the number of fatal police shootings of unarmed individuals. However, these public databases have not been validated against official records. Furthermore, there have been no attempts to explore the complexity of circumstances leading to police-related fatalities. The present study was conducted to compare information in one public database, Fatal Encounters (FE), with matched records from the King County Medical Examiner's Office (ME) and to measure the role of overlapping circumstances leading to fatal outcomes. For this purpose, the two data sources were linked by names. Circumstantial elements were extracted, categorized, and analyzed according to Manner of Death, Pre-Custody criteria, and Race assignments. Overlapping circumstances were resolved by the calculation of conditional probabilities. The results found 172 matched records in which agreements between the two sources ranged from 70% to 100%. Disagreements were present in whether the decedent was unarmed and not fleeing. The distribution of deaths according to race was disproportionate relative to the county population. The study demonstrated the importance of data in measuring police-related fatalities and the need for caution in interpreting data that does not fully encompass the range of complex circumstances.

Plants activate complex defense mechanisms against biotic and abiotic stressors, where non-specific resistance provides broad-spectrum protection. This study presents a comparative bioinformatics analysis of three membrane protein families-ABC transporters, lipid transfer proteins (LTPs), and wall-associated kinase receptors (WAKs)-in winter wheat (Triticum aestivum L.) and sunflower (Helianthus annuus L.). Using public databases, we identified 150 ABC transporters, 80 LTPs, and 55 WAKs in wheat, and 120 ABC, 65 LTPs, and 40 WAKs in sunflower. Structural analysis confirmed conserved domains, including ABC_NBD, TMD, PR-14, and WAK kinase. Transcriptomic data revealed distinct immune strategies: winter wheat effectively implements systemic acquired resistance (SAR), particularly through ABCG transporters (Lr34/Sr57 type) that modulate hormone balance and defense metabolites. In contrast, sunflower predominantly activates a rapid localized immune response (LAR), characterized by ROS signaling triggered by WAK receptors functioning as damage sensors. Functional divergence was observed: wheat WAKs and LTPs are primarily involved in cell wall remodeling and physical barrier induction, while in sunflower, they focus on signaling and membrane stabilization under oxidative stress. Our findings suggest that the evolutionary adaptation of monocots and dicots led to the functional specialization of conserved immune components according to their distinct pathogen spectra and physiological features. These results provide a molecular basis for understanding the diversity of non-specific immunity mechanisms in strategically important crops.

Human activities are driving shifts in the distribution of species. This is leading to profound changes in biological communities as some species head towards extinction while there is a spread of pathogenic organisms and non-indigenous species. For efficient and effective management of these shifts it is critical to be able to detect species of interest promptly and accurately. With technological advancements there is an increasing amount of environmental DNA data available to researchers and environmental managers, but it is often not optimally utilized for the detection of species of interest. BIOWATCH is a R shiny app which aims to improve the detection of species of interest in metabarcoding datasets. BIOWATCH enables the user to create custom reference databases from a predefined list of species from public databases. Metabarcoding datasets can then be investigated against these custom databases to detect species of interest. Users are also able to visualize the results to assess spatial and temporal patterns of those species. BIOWATCH offers a versatile platform that empowers users to interpret metabarcoding results, contributing to improved ecosystem monitoring, conservation planning, and species management in an era of rapid environmental change.

This study employed an imaging-decoding strategy to quantitatively characterize intratumoral heterogeneity (ITH) in patients with head and neck squamous cell carcinoma (HNSCC), and further evaluated the capacity of the imaging-based ITH score in prognostic stratification and immunotherapy response prediction. A total of 993 HNSCC patients from three medical centers and one public database were stratified into seven sets. Using an unsupervised radiomics framework integrating local variation and global distribution, tumor regions of interest (ROIs) and volumes of interest (VOIs) were separately analyzed to calculate 2D and 3D ITH scores. The association between the ITH score and patient prognosis was evaluated across independent prognostic sets, and its predictive performance for pathologic complete response (pCR) was assessed in an immunotherapy set. Additionally, histological and molecular characteristics of the ITH score were explored via the pathological set and the genomic set. The ITH score demonstrated robust prognostic value and good predictive performance. Biologically, low-ITH tumors exhibited a higher proportion of inflammatory and connective cells, and were enriched in immune-related pathways, whereas high-ITH tumors exhibited increased heterogeneous tumor cells and upregulation of metabolic pathways. The proposed ITH score represented a reliable, noninvasive, and biologically interpretable imaging biomarker that effectively quantified tumor heterogeneity in HNSCC.

Multiple myeloma (MM) develops with the acquisition of genetic abnormalities in plasmacytes and changes in microenvironment cells (MECs). Despite the progress in understanding MM disease mechanism through omics studies, the genomic/transcriptomic profiling remains limited in Chinese MM patients. Here, we collected 277 newly diagnosed MM (NDMM) patients in the Shanghai MM Omics (SMMO) project. Analysis of 267 cases with whole-genome/whole-exome sequencing and RNA sequencing (RNA-seq) identified three genetic groups (MY, HRD, and MS/CD). Using single-cell RNA sequencing (scRNA-seq), we investigated 59 NDMM subjects from SMMO, 20 relapsed cases from public database and 30 normal controls. Eight subpopulations of plasmacytes from NDMM (mSP1-mSP8) were defined, each showing unique signatures while forming a differentiation trajectory. The mSP2 is worth noting due to its high proliferative property. Regarding MECs, we found T cell subsets including T-helpers, Tregs, and cytotoxic T cells all in dysfunctional status and increased myeloid-derived suppressor cells such as macrophages mainly in M2 polarization, both constituting a milieu in favor of MM cell growth and immune escape. Furthermore, we scrutinized the crosstalk between MM cells and MECs and that among distinct MECs. A dynamic, comprehensive MM pathogenesis network was revealed, with a number of ligand-receptor pairs. Importantly, the mSP2 signature can be projected to the MM cell RNA-seq data of 235 patients to generate a Score100 with prognostic value in SMMO. Via multivariate analysis of the International Staging System, Consensus Genomic Staging, and Score100, we propose a practical MM stratification model for evaluating aggressive myeloma.

Methylation of zinc-finger protein ZNF471 regulates MIS18A expression and inhibits proliferation and metastasis of hepatocellular carcinoma via negative regulation of the Wnt/β-catenin pathway, as well as enhances sensitivity to apatinib and donafenib.

Purines are a class of ubiquitous molecules required for fundamental processes in all cells. Purines are derived from two major sources: de novo synthesis, and salvage of preformed purine bases. The current studies provide evidence that the relative contributions of these two pathways change substantially as human induced pluripotent stem cells (iPSCs) differentiate into neurons. Expression of all genes in the de novo synthesis pathway decreases as pluripotent cells differentiate into neurons, but expression of the salvage pathway gene HPRT1 increases. This selective rise in HPRT1 gene expression corresponds with increased activity of its associated enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Similar changes in the expression of genes for the de novo pathway genes and for HPRT1 were found in a public database of gene expression for human brain development. The consequences of eliminating HGprt-mediated recycling were also evaluated in human-derived iPSCs with null HPRT1 mutations and stock iPSC lines that have been gene-edited to contain a null HPRT1 mutation. The absence of HGprt had no apparent impact on early neuronal differentiation, through 60 days of in vitro differentiation. Biochemical studies of purine content showed that that the absence of HGprt had little impact on intracellular purines, although large amounts of its substrate (hypoxanthine) accumulated in the tissue culture medium. Neurons derived from iPSCs without HGprt appeared morphologically and neurochemically indistinguishable from neurons derived from iPSCs where HGprt was intact. Interrogation of the transcriptome using RNA sequencing (RNAseq) indicated that the absence of HGprt had no consistent impact on gene expression during differentiation. Overall, these results suggest HGprt does not have a large impact on early neuronal differentiation and may instead play a more important role in later neuronal differentiation or function.