Communications Biology

Different patterns of physical activity (PA), including sedentary behavior, have been linked to a wide range of health outcomes. However, the underlying molecular mechanisms-- particularly the biological pathways connecting distinct aspects of PA to health outcomes--are incompletely understood. In this study, we investigated the associations between 14 PA features across four categories--captured using wearable accelerometer data--and plasma protein (PP) expression levels in 9,210 individuals fr...

Exercise is effective toward delaying or preventing chronic disease, with a large body of evidence supporting its effectiveness. However, less is known about the specific healthspan-promoting effects of exercise on blood biomarkers in the disease-free population. In this work, we examine 23,237 generally healthy individuals who self-report varying weekly running volumes and compare them to 4,428 generally healthy sedentary individuals, as well as 82 professional endurance athletes. We estimate t...

Cardiometabolic diseases are multifactorial disorders influenced by numerous genetic variants and their complex interactions. Although recent studies have advanced the understanding of genetic risk prediction, current approaches predominantly rely on linear models that may not fully capture the complex, non-linear relationships between genetic factors. Here, we present DeepGP (Deep learning-based Genome-wide Predictor), a novel multimodal deep learning framework that incorporates bidirectional s...

BackgroundDisease networks offer a potential road map of connections between diseases. Several studies have created disease networks where diseases are connected either based on shared genes or Single Nucleotide Polymorphisms (SNP) associations. However, it is still unclear to which degree SNP-based networks map to empirical co-observed diseases within a different, general, adult study population spanning over a long time period. MethodsWe create a SNP-based disease network (PheNet) from a larg...

ObjectivesTo quantify the contribution of cardiorespiratory fitness (CRF) genetics in common non-communicable disease (NCD) and mortality risk and to assess whether health discrepancies exist between "inherited" and "gained" CRF. MethodsWe used a validated SBayesR-based genome-wide polygenic score, leveraging information from 905,707 single-nucleotide polymorphisms, to measure CRF genetics (PGS CRF). Associations with register-based incident cardiovascular disease, cancer, pulmonary disease, ty...

BV (bacterial vaginosis) influences 20-40% of women but its etiology is still poorly understood. An open question about the BV is which of the hundreds of bacteria found in the human vaginal microbiome (HVM) are the causal pathogens of BV? Existing attempts to identify them have failed for at least two reasons: (i) a focus on species per se that ignores species interactions; (ii) a lack of systems-level understanding of the HVM. Here, we recast the question of microbial causality of BV by asking...

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G3...

Undifferentiated pleomorphic sarcoma (UPS) remains one of the most clinically aggressive and poorly characterized soft tissue sarcoma (STS) subtypes. To uncover distinctive molecular traits for UPS, a multi-omics analysis of UPS compared to leiomyosarcoma (LMS), and liposarcoma (LPS) was performed. Transcriptomic profiling revealed that UPS exhibits overexpression of genes encoding succinate dehydrogenase (SDH) subunits, particularly SDHB, SDHC, and SDHD, distinguishing it from LMS and dediffere...

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis and limited therapies. To elucidate its post-transcriptional regulation, ceRNA networks were reconstructed from TCGA-ACC and GTEx 2025 data. Tumor networks exhibited compact topology and tumor-specific hub miRNAs (miR-466, miR-940, miR-507), which were downregulated, inversely correlated with oncogenic transcripts, and associated with adverse survival. Candidate targets were identified through dual validation ...

This study explores the multi-level regulatory roles of the lactate metabolism gene network in oral cancer development using machine learning models. Machine learning analysis shows that lactate-related gene expression profiles can effectively distinguish treatment groups from controls (AUC=0.933), with SLC16A1 and KIF2C being key features. Genes like PFKP, LDHA, LDHB, LDHC, and VCAN are highlighted for their biological relevance. PFKP, involved in glycolytic metabolic regulation, is significant...

BackgroundThe development and expansion of warm autopsy program have important implications in dissecting the heterogeneity during cancer dissemination and resistance. However, in China, the practice of warm autopsy has not yet been officially launched and documented. MethodsTo explore and establish the procedures and standards for warm autopsy in China, we followed the disease course of a male patient with terminal metastatic prostate cancer. We assembled a multidisciplinary team to perform wa...

ObjectiveThe objective of this study is to determine how NF-{kappa}B-mediated inflammation disrupts pancreatic signaling pathways and the resultant increase in the risk of Pancreatic Adenocarcinoma. BackgroundPancreatic adenocarcinomas severity and poor prognosis underscore the critical role of NF-{kappa}B-mediated inflammation in disease progression. NF-{kappa}B activation disrupts key pancreatic signaling pathways by promoting cell proliferation, inhibiting differentiation, and facilitating o...

BackgroundOlfactory receptors (ORs) are G protein-coupled receptors that are aberrantly expressed in various cancers, including clear cell renal cell carcinoma (KIRC). However, the roles of ORs in KIRC are unknown. This study aimed to comprehensively analyze the expression profiles of OR genes in KIRC and evaluate their potential as diagnostic and prognostic biomarkers. MethodsWe analyzed RNA-seq data from The Cancer Genome Atlas KIRC dataset, which contains 72 normal and 530 tumor samples. We ...

BackgroundPancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with limited therapeutic advancements and rapid development of treatment resistance. Fatty acid-conjugated gemcitabine analogs have shown improved antitumor efficacy. This study investigates the effects of gemcitabine conjugated with caprylic acid (Gemcitabine-8C) in combination with AZD 1775, a WEE1 inhibitor, using patient-derived PDAC organoids. MethodsPatient-derived PDAC cells (G43, G46) were cultured in a ...

The initiation and progression of breast cancer (BRCA) is associated with inflammation and immune-overactivation. The E3 ubiquitin ligase is known to subtly balance immune-overactivation and pro-tumorigenesis. Here, by global transcriptional profiling of BRCA patient tissues, we identified a signature expression profile of F-box factors, of which FBXL8 emerged as a novel key component of E3 ligase. Our ex vivo studies (n=1349) indicate that FBXL8 promotes tumorigenesis and its level escalates wi...

Despite advancements in therapeutics, Bladder Cancer (BLCA) constitutes a major clinical burden, with locally advanced and metastatic cases facing poor survival rates. Aiming at expanding our knowledge of BLCA molecular pathophysiology, we integrated 1,508 publicly available, primary, well-characterized BLCA transcriptomes and investigated alterations in gene expression with stage (T0-Ta-T1-T2-T3-T4). We identified 157 genes and several pathways related prominently with cell cycle, showing a mon...

Polo-Like Kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a novel hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a new HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response elemen...

High throughput serological tests that can establish the presence and functional activity of anti-SARS-COV2 antibodies are urgently needed. Here we present microsphere-based Flow Cytometry assays that quantify both anti-spike IgGs in plasma, and the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). First, we detected anti-spike-trimer IgGs in 22/24 and anti-spike-receptor-binding-domain (RBD) IgGs in 21/24 COVID+ subjects at a median of 36 (rang...

(1) BackgroundRecent studies suggest a potential link between gut microbiomes (GMs) and inflammatory diseases, but the role of GMs in lichen sclerosus (LS) remains unclear. This study aims to investigate the causal relationship between GMs and LS, focusing on key GM taxa. (2) MethodsWe utilized GWAS summary statistics for 211 GM taxa and their association with 2,445 LS patients and 353,088 healthy controls, employing Mendelian randomization (MR). GWAS data for GM taxa came from the MiBioGen con...

BackgroundPancreatic ductal adenocarcinoma (PDAC) critically depends on oncogenic KRAS signaling. The Src-homology 2 domain-containing phosphatase 2 (SHP2) is essential for full KRAS activity. Allosteric SHP2 inhibition in vertical combination with mitogen-activated protein kinase (MAPK) or RAS inhibition demonstrates synergistic efficacy, delays the onset of resistance, and is currently being evaluated in clinical trials. MethodsEmploying a comprehensive set of models, including endogenous mur...