Biology subjects

Zhou, Z.

Publications and source records attributed to Zhou, Z..

At least 145 records · Page 8Linked to original sources

bioRxiv2025

Gut bacteria degrade purines via the 2,8-dioxopurine pathway

The loss of uricase during hominid evolution has predisposed humans to hyperuricemia and gout, conditions with high global prevalence. In healthy individuals, approximately one-third of urate is excreted into the intestinal tract1 where bacteria consume this purine aiding in its elimination2,3. However, the molecular details of purine metabolism in the gut microbiome remain unknown. Here we uncover the 2,8-dioxopurine pathway, a previously unrecognized anaerobic route for purine degradation in gut bacteria. This pathway uses a novel selenium-dependent enzyme, 2,8-dioxopurine dehydrogenase (DOPDH), and seven additional enzymes that together link purine metabolism to ATP generation and short chain fatty acid production. Competition experiments in gnotobiotic mice demonstrate that bacteria harboring this pathway exhibit a fitness advantage, with wild-type bacteria rapidly outcompeting a DOPDH-deficient strain. These findings highlight a host-microbe symbiosis, where host-secreted urate fosters a metabolic niche for bacteria that break it down. By elucidating this pathway, our study provides new avenues to modify and enhance intestinal elimination of urate, which has therapeutic implications for treating hyperuricemia and gout, conditions that affect millions of adults worldwide.

microbiology↗

bioRxiv2025

TWIST1 mediated transcriptional activation of SPON2 drives colorectal peritoneal metastasis through activation of cancer-associated fibroblast signaling network

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related mortality in the United States. Peritoneal metastasis (PM), a malignant dissemination within the peritoneal cavity, affects approximately 20% of CRC patients and accounts for 25-35% of stage IV cases. CRC PM is associated with dismal outcomes, with a median overall survival of only 16 months on systemic chemotherapy and an almost 0% five-year survival rate, largely due to frequent treatment resistance and limited therapeutic options. Despite advances in understanding CRC metastasis, the molecular mechanisms driving CRC PM remain poorly defined. CRC heterogeneity is classified into four Consensus Molecular Subtypes (CMS1-4), with CRC PM tumors predominantly exhibiting the CMS4 signature--characterized by stromal enrichment, high mesenchymal gene expression, and enhanced cellular plasticity--features linked to aggressive disease progression and resistance to standard chemotherapy. In this study, we identify TWIST1, a basic helix-loop-helix transcription factor, as significantly upregulated in CRC PM. We establish TWIST1-SPON2 as a novel transcriptional axis driving CRC PM tumorigenesis, mediating tumor-stroma interactions between tumor epithelium and cancer-associated fibroblasts (CAFs). Additionally, we identify SPP1, secreted by CAFs, as an upstream regulator of the TWIST1-SPON2 cascade via AKT activation in tumor cells. This newly defined SPP1-TWIST1-SPON2 signaling circuit plays a pivotal role in shaping the tumor microenvironment and promoting CRC PM progression. The findings establish the SPP1-TWIST1-SPON2 axis as a potential biomarker and a promising therapeutic target in CRC PM. Keyword: Colorectal cancer, peritoneal metastasis, epithelial-mesenchymal transition, cancer-associated fibroblast

cancer biology↗

bioRxiv2025

Harmful algal bloom species Microcystis aeruginosa releases thiamin antivitamins to suppress competitors

In environmental ecosystems, vitamin concentrations are often exceedingly low (1, 2) and auxotrophy, or reliance on exogenous vitamin or vitamin precursors, is widespread (3-5). We show here that the widespread harmful algal bloom (HAB) species Microcystis aeruginosa, threatening freshwater aquatic ecosystems globally, releases a complex mixture of thiamin antivitamins, including bacimethrin and methoxythiamin, which induce thiamin deficiency in the benign model green alga Chlamydomonas reinhardtii. Putative biosynthetic genes for bacimethrin were upregulated in M. aeruginosa when grown in co-culture resulting in greater production of bacimethrin. Bacimethrin, methoxythiamin, oxidized forms of thiamin and methoxythiamin, and a novel structural homolog of bacimethrin were all found at elevated levels in the co-culture exometabolome extracts and were all inhibitory to the growth of C. reinhardtii individually at very low concentrations and as a mixture in culture medium extracts. The thiamin-requiring mutant C. reinhardtii, CC-25, was much more sensitive to bacimethrin and methoxythiamin than the wildtype. Thiamin addition largely rescued the inhibitory effects of exposure to antivitamins in both the wildtype and mutant strain. Finally, we determined that bacimethrin is present in aquatic environments and is elevated during Microcystis blooms. Thus, allelopathic suppression of competitors, particularly those that are auxotrophic for thiamin, by M. aeruginosa via the production of antivitamins in environments where thiamin availability is low, could help this species to become dominant and form blooms.

microbiology↗

bioRxiv2025

Cold-activated hepatocyte derived exosomes promote BAT thermogenesis through miR-293-5p

The liver-adipose axis serves as a fundamental regulatory network governing systemic lipid homeostasis, with hepatic-derived signals orchestrating adipose tissue plasticity through multimodal mechanisms. Comprehensive elucidation of these bidirectional crosstalk mechanisms may reveal novel therapeutic strategies for metabolic disorders. Our investigation demonstrates that cold exposure induces hepatic secretion of exosomes that potentiate adipose thermogenic activation in both in vitro and in vivo models. This thermogenic potentiation is mechanistically linked to cold-induced upregulation of hepatocyte-derived exosomal miR-293-5p. Notably, pharmacological administration of miR-293-5p agomir significantly attenuates diet- induced obesity and associated metabolic dysregulation in murine models. Through mechanistic interrogation, we identified Tet1 as a direct downstream target of miR- 293-5p, where ectopic Tet1 expression disrupts brown adipose tissue (BAT) thermogenic programming independently of miR-293-5p modulation. Our findings establish cold-activated hepatocyte exosomes as endocrine signaling mediators containing thermogenic microRNA cargos, with miR-293-5p emerging as a regulatory nexus coordinating mitochondrial bioenergetics and systemic energy equilibrium through liver-adipose cross-talk.

genetics↗

bioRxiv2025

Non-invasive skin topical delivery of hyaluronan

Hyaluronic acid (HA), a key glycosaminoglycan in the skin extracellular matrix, diminishes with aging, leading to dryness, wrinkles, and loss of elasticity. While subcutaneous HA injection remains the standard treatment, it is invasive and associated with complications. Here, we developed a zwitterionic polymer-based nanogel system (HA/OP) for noninvasive transdermal HA delivery. The nanogels, formed by complexing HA with poly[2-(N-oxide-N,N-diethylamino)ethyl methacrylate] (OP), exhibited pH-responsive behavior, remaining stable at weakly acidic skin surface pH ([~]5) but dissociating in neutral dermal environments. HA/OP nanogels efficiently permeated the stratum corneum via sebum-assisted enrichment and para-corneocyte transport, followed by transcytosis and enhanced paracellular penetration mediated by myosin light-chain kinase (MLCK) upregulation. This enabled deep HA deposition in the dermis and subcutaneous tissue, significantly improving skin hydration and reducing wrinkles in hairless mice without irritation. Our findings present a safe, needle-free strategy for topical HA delivery, addressing a major unmet need in cosmetic and dermatological applications.

bioengineering↗

bioRxiv2025

Object categorization based on abstract concepts by monkeys, humans, and vision models

Humans categorize objects at multiple levels of abstraction--animate versus inanimate, big versus small, and many other attributes. Despite its apparent challenge, the advent of deep neural networks (DNNs) has demonstrated that complex visual processing alone can support such classification without language or human-specific knowledge. This raises a natural question: to what extent can non-human primates, without language, perform such categorization? Although basic object-recognition behavior in monkeys such as similarity judgment has been extensively studied, their ability to classify objects across diverse rules remains poorly characterized. Here, we developed a task paradigm that enabled us to train monkeys on a large battery of binary classification tasks using natural object images, spanning more than 10 rules, such as animate versus inanimate, natural versus man-made objects, and mammalian versus non-mammalian animals. Monkeys acquired each rule in a few days, generalized the learned rules to new images, and exhibited error patterns consistent with human judgments. At the same time, their classification performance correlated more strongly with that of visual DNNs trained without language input, whereas human performance was better explained by language-informed DNNs. These results provide an important benchmark for the capacity of biological neural networks to perform image classification without language and human-specific knowledge.

neuroscience↗

bioRxiv2025

Integrative Machine Learning and Bioinformatics Analysis to Identify Cellular Senescence-Related Genes and Potential Therapeutic Targets in Ulcerative Colitis and Colorectal Cancer

BackgroundUlcerative colitis (UC) is a chronic inflammatory condition that predisposes patients to colorectal cancer (CRC) through mechanisms that remain largely undefined. Given the pivotal role of cellular senescence in both chronic inflammation and tumorigenesis, we integrated machine learning and bioinformatics approaches to identify senescence{square}related biomarkers and potential therapeutic targets involved in the progression from UC to CRC. MethodsGene expression profiles from six GEO datasets were analyzed to identify differentially expressed genes (DEGs) using the limma package in R. Weighted gene co expression network analysis (WGCNA) was employed to delineate modules significantly associated with UC and CRC, and the intersection of DEGs, key module genes, and senescence related genes from the CellAge database yielded 112 candidate genes. An integrated machine learning (IML) model, utilizing 12 algorithms with 10 fold cross validation was constructed to pinpoint key diagnostic biomarkers. The diagnostic performance of the candidate genes was evaluated using receiver operating characteristic (ROC) analyses in both training and validation cohorts. In addition, immune cell infiltration, protein protein interaction (PPI) networks, and drug enrichment analyses, including molecular docking were performed to further elucidate the biological functions and therapeutic potentials of the identified genes. ResultsOur analysis revealed significant transcriptomic alterations in UC and CRC tissues, with the turquoise module demonstrating the strongest association with disease traits. The IML approach identified five pivotal genes (ABCB1, CXCL1, TACC3, TGFBI, and VDR) that individually exhibited AUC values >0.7, while their combined diagnostic model achieved an AUC of 0.989. Immune infiltration analyses uncovered distinct immune profiles correlating with these biomarkers, and the PPI network confirmed robust interactions among them. Furthermore, drug enrichment and molecular docking studies identified several promising therapeutic candidates targeting these senescence{square}related genes. ConclusionsThis study provides novel insights into the molecular interplay between cellular senescence and the UC to CRC transition. The identified biomarkers not only offer strong diagnostic potential but also represent promising targets for therapeutic intervention, paving the way for improved clinical management of UC associated CRC.

bioinformatics↗

bioRxiv2025

Comprehensive Evaluation of Diverse Massively Parallel Reporter Assays to Functionally Characterize Human Enhancers Genome-wide

Massively parallel reporter assays (MPRAs) and self-transcribing active regulatory region sequencing (STARR-seq) have revolutionized enhancer characterization by enabling high-throughput functional assessment of regulatory sequences. Here, we systematically evaluated six MPRA and STARR-seq datasets generated in the human K562 cell line and found substantial inconsistencies in enhancer calls from different labs that are primarily due to technical variations in data processing and experimental workflows. To address these variations, we implemented a uniform enhancer call pipeline, which significantly improved cross-assay agreement. While increasing sequence overlap thresholds enhanced concordance in STARR-seq assays, cross-assay consistency in LentiMPRA was strongly influenced by assay-specific factors. Notably, our results show that LentiMPRA exhibits a strong preference for promoter-associated sequences rather than enhancers. Functional validation using candidate cis-regulatory elements (cCREs) confirmed that epigenomic features such as chromatin accessibility and histone modifications are strong predictors of enhancer activity. Importantly, our study validated transcription as a critical hallmark of active enhancers, demonstrating that highly transcribed regions exhibit significantly higher active rates across assays. Furthermore, we show that transcription enhances the predictive power of epigenomic features, enabling more accurate and refined enhancer annotation. Our study provides a comprehensive framework for integrating different enhancer datasets and underscores the importance of accounting for assay-specific biases when interpreting enhancer activity. These findings refine enhancer identification using massively parallel reporter assays and improve the functional annotation of the human genome.

genomics↗

bioRxiv2025

Metabolic reinvigoration of NK cells by IL-21 enhances immunotherapy against MHC-I deficient solid tumors

Natural killer (NK) cells, a type of potent cytotoxic lymphocytes, are particularly promising for the treatment of cancers that lose or downregulate major histocompatibility complex class I (MHC-I) expression to evade T cell-mediated immunotherapy. However, the hostile and immune suppressive tumor microenvironment (TME) greatly hinders the function of tumor-infiltrating NK cells limiting the therapeutic efficacy against solid tumors. Here, we show that a fusion protein of interleukin-21 (IL-21-Fc), as a direct in vivo intervention, can safely and effectively reprogram NK cell metabolism and enhance their effector function in the TME. Our research demonstrates that combining IL-21-Fc with IL-15 superagonist (IL-15SA) or NK cell transfer leads to the eradication of MHC-I-deficient tumors and confers durable protection in syngeneic and xenograft tumor models. Mechanistically, we uncover that IL-21-Fc enhances NK cell effector function by upregulating glycolysis in a lactate dehydrogenase A (LDHA)-dependent manner. These findings not only underscore the considerable potential of IL-21-Fc as an in vivo therapeutic intervention to bolster NK cell-based immunotherapy, but also unveil an innovative strategy of metabolic reprogramming for NK cell rejuvenation within tumors. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/643961v2_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@daf24forg.highwire.dtl.DTLVardef@5a5029org.highwire.dtl.DTLVardef@144c978org.highwire.dtl.DTLVardef@106ed1c_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LINK cells display functional exhaustion in MHC-I deficient solid tumors C_LIO_LIIL-21-Fc as an in vivo-applicable and safe immunotherapy reinvigorates intratumoral NK cells for enhanced effector function C_LIO_LIIL-21-Fc enhances NK cell function by elevating glycolysis in a LDHA-dependent manner C_LIO_LICombining IL-21-Fc with low-dose IL-15SA or NK cell transfer eradicates syngeneic and xenografted solid tumors C_LI

cancer biology↗

bioRxiv2025

Manganese suppresses tumor growth through hyper-activating IRE1α

IRE1 and its downstream XBP1 signal is the most conserved unfolded protein response pathway that cells utilize to combat endoplasmic reticulum stress, also known to be utilized by tumor cells to adapt to harsh environment, leading to tumor progression. Several inhibitors against IRE1 have been developed, some of which show promising effect in clinical trial for cancer therapy, but none of them have been used in practice. Considering that hyper-activation of IRE1 induces cell death, we hypothesize that activation of IRE1 could be an alternative way for tumor suppression. Here, we identified divalent manganese ion as a potent activator to IRE1, which interacts with the cytosolic part of IRE1 directly, augmenting the downstream pro-apoptotic pathway but not the pro-survival outcome. Mn2+ limits tumor growth in xenograft model in an IRE1-dependent way. Our finding suggests pharmacological activation of IRE1 as an underestimated but promising way in cancer therapy. HighlightsO_LIMn2+ binds to cytosolic segment of IRE1 and promotes its oligomerization C_LIO_LIMn2+ hyper-activates IRE1 and induces downstream terminal UPR under ER stress C_LIO_LIMn2+ does not elevate XBP1s expression C_LIO_LIMn2+ as an IRE1 activator impairs tumor growth in xenograft model C_LI

cancer biology↗

bioRxiv2025

Red Light-Activated Reversible Inhibition of Protein Functions by Assembled Trap

Red light offers strong tissue penetration and low phototoxicity, making it an attractive option for optogenetic applications. However, the available red light-inducible optogenetic tools are rather limited. Here, we present a novel red light-induced protein clustering system, namely R-LARIAT (Red Light-Activated Reversible Inhibition by Assembled Trap), that controls protein functions in a spatiotemporal manner. Our system capitalizes on the rapid and reversible binding of LDBs (nanobodies-based dimerization binders) to a bacterial phytochrome DrBphP, which uses a mammalian endogenous biliverdin chromophore to absorb red light. An anti-GFP nanobody fused with LDBs allows this method to quickly trap a wide variety of GFP-tagged proteins into light-induced protein clusters. Strikingly, our system exhibits an excellent performance in clustering efficiency with high light sensitivity and stability, it can function even when shielded by multiple glass plates. By utilizing the R-LARIAT system to trap and sequester tubulin, cell cycle progression can be blocked in HeLa cells. Therefore, the R-LARIAT system takes advantage of red light with greater tissue penetration and holds the potential to precisely control protein functions in living organisms.

cell biology↗

bioRxiv2025

A METHOD TO CALIBRATE CHEMICAL AGNOSTIC QUANTITATIVE ADVERSE OUTCOME PATHWAYS ON MULTIPLE CHEMICAL DOSE-RESPONSE DATA

Quantitative Adverse Outcome Pathways (qAOPs) may support next-generation risk assessment by integrating New Approach Methodologies (NAMs) for derivation of points of departure. To be useful, a qAOP should be chemical-agnostic. However, existing qAOP studies often pool multi-chemical data without adequately addressing inter-chemical heterogeneity. Consequently, fundamental pathway relationships become obscured by heterogeneity-induced noise, thereby compromising the reliability of chemical-agnostic predictions. We developed a chemical-agnostic calibration approach to addresses this challenge by leveraging hierarchical structures to systematically separate chemical-specific heterogeneity from underlying pathway effects. Through this methodological framework, chemical-specific deviations are explicitly modeled as random effects, enabling the extraction of pathway-level parameters that represent core mechanistic relationships independent of individual chemical properties. Through simulation studies across varying heterogeneity levels, we demonstrate that performance differences between models with and without hierarchical calibration reveal the magnitude of heterogeneity in the data. Moreover, when heterogeneity is substantial, an uncalibrated qAOP should not be considered truly chemical-agnostic in practice, as it confounds pathway-level effects with chemical-specific variation. We demonstrated the application of this calibration approach through a case study of non-mutagenic liver tumor. The framework proposed in this study enhances qAOP generalizability while preserving the chemical-agnostic principle, supporting robust NAMs-based next-generation risk assessments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/642550v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@e7011eorg.highwire.dtl.DTLVardef@1fa7be9org.highwire.dtl.DTLVardef@1dd0b52org.highwire.dtl.DTLVardef@1123a93_HPS_FORMAT_FIGEXP M_FIG Figure 1: For TOC only C_FIG

bioinformatics↗

bioRxiv2025

Improved Prediction of Bacterial Type VI Secretion Effector Proteins Using an Integrated Convolutional Neural Network Model Combining N-terminal Signal Sequences, Evolutionary Information and Pre-Trained Protein Language Features

Type VI secretion system effectors (T6SEs) are crucial for bacterial pathogenicity, making their accurate identification essential for understanding bacterial virulence mechanisms. This study analyzed the differences in amino acid composition of N-terminal signal sequences between T6SEs and non-T6SEs, uncovering distinct positional amino acid preferences in T6SEs. Using a combination of unsupervised and supervised analysis, we evaluated feature encoding methods and developed T6CNN, an ensemble model that integrates N-terminal signal sequences, evolutionary information, and pre-trained protein language features for T6SE prediction. T6CNN demonstrated outstanding performance in independent testing, outperforming existing tools with a 7.9% accuracy increase (to 0.953), a 13.2% sensitivity improvement (to 0.964), and a 6.6% specificity enhancement (to 0.951). The T6CNN model offers a reliable and accurate solution for T6SE prediction, with significant potential to advance research on bacterial pathogenicity. ImportanceThis study introduces T6CNN, a new computational model for identifying Type VI secretion system effectors used by harmful bacteria. By analyzing early protein sequences, T6CNN uncovers unique features that reliably distinguish effector proteins. Integrating evolutionary data and pre-trained protein language features, the model outperforms existing methods in accuracy, sensitivity, and specificity. This enhanced prediction tool deepens our understanding of bacterial infection mechanisms and offers researchers a valuable resource for pinpointing key virulence factors. Ultimately, T6CNN may help drive the development of more targeted antibacterial treatments and strategies to combat bacterial diseases.

bioinformatics↗

bioRxiv2025

Recurrent patterns of widespread neuronal genomic damage shared by major neurodegenerative disorders

Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimers disease (AD) represent two major categories of neurodegenerative disorders--TDP-43 and tau proteinopathies--for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 469 neurons from C9ORF72 ALS, C9ORF72 FTD, AD, and control brains revealed increased somatic single nucleotide variants (sSNVs) and insertions/deletions (sIndels) in all three diseases. Mutational signature analysis identified a disease-associated sSNV signature consistent with oxidative damage and an sIndel process affecting 22% of ALS, 76% of FTD, and 61% of AD neurons--but only 2% of control neurons--resembling signature ID4, previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Rapid Approach to DNA Adduct Recovery (RADAR) assays confirmed increased TOP1-DNA covalent complexes and duplex sequencing confirmed the increased sIndels and identified single-strand events as likely precursor lesions. TOP1-associated sIndel mutagenesis and genome instability thus represents a mechanism shared by both TDP-43 and tau neurodegeneration.

genomics↗

bioRxiv2025

Trimethylamine-N-oxide affects cell type-specific pathways and networks in mouse aorta to promote atherosclerotic plaque vulnerability

BackgroundTrimethylamine-N-oxide (TMAO) has been significantly linked to atherosclerosis via several mechanisms, but its direct effect on the atherosclerosis-prone vasculature remains unclear. The objective of this study was to characterize the cell type-dependent and independent effects of TMAO on key vascular cell types involved in atherosclerosis progression in vivo. MethodsWe performed single cell RNA-sequencing (scRNAseq) on aortic athero-prone regions of female Ldlr-/- mice fed control Chow, high-cholesterol (HC), or HC+TMAO diets for three months to identify which aortic cell types, differentially expressed genes, and biological pathways are affected by TMAO. We also modeled cell-cell communications and intracellular gene regulatory networks to identify gene networks perturbed by TMAO feeding. Key genes and pathways were validated using primary human smooth muscle cells exposed to TMAO. Changes in the thickness of lesional fibrous caps in response to TMAO in female Ldlr-/- mice fed HC+TMAO versus HC diets were measured using transgelin immunostaining. ResultsOur scRNAseq analysis revealed that TMAO supplementation upregulated apoptotic gene signatures and downregulated extracellular matrix (ECM) organization and collagen formation genes in a subset of atherosclerosis-specific modulated vascular smooth muscle cells (vSMCs). We also identified "degradation of the ECM" as a top pathway for SMC-derived macrophage DEGs in response to TMAO. Network analyses support that macrophage-vSMC communication mediates ECM remodeling. Using human smooth muscle cells exposed to TMAO in vitro, we confirmed the direct effect of TMAO on regulating collagen and apoptotic genes. In agreement with the changes in these pathways that affect plaque stability, we observed a significant decrease in fibrous cap thickness in mice supplemented with TMAO. ConclusionsOur results reveal the effects of TMAO on vSMCs to promote apoptosis and decrease ECM formation, and on macrophage-mediated ECM degradation in atherosclerotic lesions to in concert enhance plaque instability. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/640205v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@100254org.highwire.dtl.DTLVardef@109155aorg.highwire.dtl.DTLVardef@158d280org.highwire.dtl.DTLVardef@63d544_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIscRNAseq of the aortic athero-prone regions in female Ldlr-/- mice supplemented with TMAO in the diet revealed the effect of TMAO across cell types, particularly in SMC-derived macrophages and atheroprotective modulated vSMCs. C_LIO_LITMAO increases apoptotic gene signatures and reduces ECM organization and collagen formation gene signatures in modulated vSMCs in vivo, and in vitro exposure studies support a direct effect of TMAO on these genes. C_LIO_LIModulated vSMC-specific gene regulatory networks enriched for apoptotic genes and ECM organization genes were organized by intracellular regulators such as Ccl19 and Tnn and extracellular regulators such as Mmp9 and Spp1 from macrophages. C_LIO_LIFibrous cap thickness, a marker of atherosclerotic plaque stability, was significantly reduced in female Ldlr-/- mice fed HC+TMAO versus HC diets for five months. C_LI

physiology↗

bioRxiv2025

Association Between Dietary Vitamin B1 and the Risk of Endometriosis: A Cross-Sectional Study Based on NHANES 2003-2006

Endometriosis is a chronic gynecological condition influenced by inflammation and oxidative stress. Dietary vitamin B1 plays a role in reducing oxidative stress, which may influence endometriosis risk. However, limited research explores this association. ObjectiveTo investigate the association between dietary vitamin B1 intake and the risk of endometriosis, using NHANES 2003-2006 data. Vitamins B2 and B6 are included as reference comparisons. MethodsData from 2,462 participants in NHANES 2003-2006 were analyzed. Logistic regression models were used to examine the association between vitamin B1 intake and endometriosis risk, with adjustments for covariates. Subgroup analyses and restricted cubic spline (RCS) regressions were applied to assess non-linear relationships. Vitamins B2 and B6 served as reference nutrients for comparison. ResultsVitamin B1: Higher intake of dietary vitamin B1 was significantly associated with reduced risk of endometriosis (OR = 0.76, 95% CI: 0.58- 0.99, P = 0.044 in Model 4). Vitamin B2 and B6: No significant associations were observed (P > 0.05). RCS regression demonstrated a non-linear relationship for vitamin B1, with a protective effect observed at intake levels > 1.84 mg/day. ConclusionHigher dietary vitamin B1 intake is associated with a reduced risk of endometriosis. While B2 and B6 showed no significant associations, their trends provide additional insight for future research.

cancer biology↗

bioRxiv2025

Single-nuclear transcriptomics of lymphedema-associated adipose reveals a pro-lymphangiogenic stromal cell population

Chronic lymphedema is a progressive, disfiguring disease that results from dysfunction of the lymphatic vasculature, causing distal accumulation of interstitial fluid, localized development of tissue edema, and expansion of subcutaneous adipose tissue (SAT). As the molecular mechanisms governing SAT remodeling in this disease are unclear, we performed single-nucleus RNA sequencing on paired control and affected SAT biopsies from patients with unilateral lymphedema. Lymphedema samples were characterized by expansion of SAA+ adipocytes, pro-adipogenic stem cells, and proliferation of lymphatic capillaries. A GRIA1+ lymphedema-enriched stromal cell population expressing VEGFC, ADAMTS3, and CCBE1 was identified, suggesting an enhanced axis of communication between adipose stem and progenitor cells (ASPCs) and lymphatic endothelial cells. Furthermore, lymphedema ASPC-conditioned media promoted lymphatic endothelial tube elongation and proliferation in vitro. These findings indicate a critical role for ASPCs in regulating adipocyte differentiation and lymphatic vascular remodeling in lymphedema, and provide a valuable resource for better understanding this disease.

cell biology↗

bioRxiv2025

Multi-Omics Analysis of Wound Microbiome and Staphylococcus aureus in Pressure Ulcer

This study employs a multi-omics approach to investigate the wound microbiome and Staphylococcus aureus in pressure ulcers. Metagenomic sequencing and associated technologies were utilized to examine bacterial populations, identify dominant species, and study biofilm formation in S. aureus through metabolomic and proteomic characteristics. The results revealed a significant reduction in microbial diversity in pressure ulcer samples compared to controls, with Staphylococcus, Corynebacterium, and Klebsiella being the most prevalent genera. Functional prediction analysis indicated differences in pathogenic invasiveness and biofilm formation factors among the groups. The presence of antimicrobial resistance genes was higher in the pressure ulcer group, particularly in Staphylococcus spp. strains. Whole-genome sequencing of 29 S. aureus isolates identified various clonal complexes and spa types, with the majority possessing genes conferring resistance to {beta}-lactam antimicrobials and virulence factors. Histopathological examination and fluorescent in situ hybridization confirmed the presence of S. aureus in biofilm structures. In vitro biofilm formation tests and metabolomic and proteomic analyses provided insights into the interactions between S. aureus strains and their biofilm formation, revealing enriched pathways related to metabolic processes and membrane composition. This research offers a scientific foundation for understanding the colonization patterns of S. aureus biofilms in pressure ulcer wounds.

microbiology↗