Biology subjects

Jiang, G.

Publications and source records attributed to Jiang, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Parvalbumin interneuron maturation reorganizes cortical population activity structure during development

During brain development, spontaneous cortical activity undergoes a dramatic transformation from highly synchronous network events to less correlated and sparse neuronal firing that is thought to underlie more flexible neural coding. However, how the structure of population activity changes across this transition, what circuit mechanisms drive this reorganization, and the implications for information encoding have not been fully established. Using longitudinal in vivo calcium imaging in early postnatal mice, we demonstrate that cortical network desynchronization during the second postnatal week is accompanied by a redistribution of fractional variance from dominant, low-dimensional modes into many weaker dimensions, and a growing influence of GABAergic interneurons (INs) on the network. All-optical circuit interrogation revealed that parvalbumin (PV) INs, but not somatostatin (SST) INs, are sufficient to desynchronize the network and shift the distribution of population variance. Through targeted ablation of a fraction of PV INs, we show dimensionality is highly correlated with stimulus decoding accuracy. Furthermore, PV INs undergo a sharp increase in transcriptional maturation between postnatal day (P) 8 and 11, during which they preferentially enrich for synaptic genes. Lastly, a novel, biologically plausible, multi-cell-type computational model reproduced the developmental desynchronization and rise in dimensionality. Strikingly, without being constrained by perturbation data, the model accurately predicted the effects of each IN class on the network that we observed empirically.

neuroscience↗

bioRxiv2026

A naturally occurring Tat R52W variant in brain-derived HIV attenuates transcription and may contribute to reservoir persistence

HIV-1 persistence under suppressive antiretroviral therapy (ART) remains a major barrier to eradication, yet the contribution of naturally occurring viral variation to transcriptional regulation is incompletely understood. Here, we identify an HIV-1 Tat variant (R52W) that attenuates viral transcription through the disruption of the Tat-TAR RNA interaction. Full-length HIV-1 genomes derived from the brain microglia of a Last Gift donor, together with peripheral viral sequences obtained during suppressive ART, revealed the presence of the R52W variant in vivo. The same R52W variant was found in another virally suppressed donor within the same cohort. Additional analysis of 3,440 clinical blood isolates from people with HIV identified R52W in 73 sequences (2.12%) of individuals, including three on ART and a therapy controller, and across diverse viral subtypes. Structural modeling demonstrated that R52W destabilizes Tat-TAR binding, while functional assays showed markedly reduced Tat-mediated transcriptional activity, which was restored upon tryptophan-to-arginine reversion (W52R) in Tat. These findings establish a direct molecular mechanism by which a naturally occurring HIV-1 variant modulates viral transcriptional output. Together, our results identify transcriptionally attenuated HIV-1 variants in treated individuals and suggest that modulation of Tat-dependent transcription may represent an underappreciated determinant of viral persistence under suppressive ART.

microbiology↗

bioRxiv2026

SPP1+ Microglia Are Associated with Neuroimmune Rewiring and Glutamatergic Neuronal Injury in ART-Suppressed People Living with HIV

Abstract Antiretroviral therapy (ART) effectively suppresses systemic HIV replication but does not eradicate viral reservoirs in the brain, where their identity and contribution to neurological injury remain poorly defined. Using bulk, single-cell, and single-nucleus transcriptomics of postmortem human brain tissue, we identify an activated SPP1 microglial population that expands 5.8-fold during ART and serves as the primary central nervous system (CNS) reservoir, preferentially harboring HIV transcripts. These reservoir microglia adopt a distinct, immune-evasive reprogramming state marked by chronic type I interferon signaling and inflammasome activation, which we recapitulate in primary human microglia via prolonged interferon-{beta} exposure. We show that viral transcription in ART-suppressed brains is dominated by nef, which may sustain the viral reservoir by disrupting host HLA-A and HLA-E presentation machinery. This persistent, immune-evasive state is associated with TREM2-C1QC complement-mediated synaptic pruning and severe DNA damage response dysregulation, culminating in a profound loss of VGLUT1 and GAD67 glutamatergic neurons that persists despite viral suppression. Our findings establish SPP1 microglia as an active, pathogenic CNS reservoir, identifying the SPP1, MHC-I, and complement pathways as therapeutic targets to eliminate viral persistence and reverse HIV-associated neurocognitive dysfunction.

neuroscience↗

bioRxiv2026

Rate of meristem initiation driven by the MADS-WUS axis contributes to floral survival and inflorescence evolution in grasses

Crop domestication has repeatedly shaped inflorescence architecture to improve floral production, but mechanisms coordinating the rate of floral initiation, maturation and survival remain unclear. Combining morphometry, modelling and molecular genetic analyses, we show that floral production in the indeterminate barley (Hordeum vulgare L.) inflorescence follows an "initiate fast-die young" strategy orchestrated by a main MADS-box gene, SPIKELET INITIATION AND FERTILITY (SIF). SIF accomplishes this duality by coordinately terminating the inflorescence meristem via WUSCHEL and activating the floral meristem via APETALA1 (Vrn-H1). Hereby, the ancestral SIF "slow" allele promotes a timely commitment to floral maturation, whereas the derived "fast" allele permits more floral initiations. Postdomestication selection of SIF alleles thus enables diversified reproductive strategies in barley populations to maintain yield traits in the field. Finally, we show that a lineage-specific SIF duplication contributed to meristem fate transition and inflorescence evolution during Triticeae cold adaptation. Our results establish developmental rate as a key driver of architectural innovation and reproductive success.

plant biology↗

bioRxiv2026

CBR4 is essential for mice but not for skeletal muscle function

The mitochondrial fatty acid synthesis (mtFAS) pathway is a highly conserved process in mitochondria implicated in metabolic state sensing. Aberrant functioning of this pathway leads to neurodegenerative diseases in humans. Animal experiments indicates that the mtFAS pathway is essential in mammals, and mtFAS inactivation leads to neuronal cell death. Nuclear encoded mitochondrial 3-ketoacyl-acyl carrier protein reductase (KAR) is a heterotetrameric enzyme in this process, consisting of two CBR4 and two HSD17B8 polypeptides. CBR4 works as the catalytic subunit of the enzyme. Here, we provide evidence that CBR4 function is essential in mammals. In contrast, a skeletal muscle-specific Cbr4 KO in mice did not result in any measurable defects in muscle strength and endurance, and the overall structure of the muscle remained unchanged. The Cbr4 KO did not affect the lipoylation process in quadriceps muscle samples, and high-resolution respirometry analysis of soleus muscle samples showed no defects in mitochondrial respiration capacity. The lack of a phenotype of a muscle-specific Cbr4 KO is consistent with previous reports on a lack of effects of mtFAS inactivation in muscle and re-iterates the question about the existence of bypass mechanisms that can alleviate mtFAS deficiencies in non-neuronal cell types.

physiology↗

bioRxiv2026

Cohesin collisions maintain ordered nucleosome architecture at boundaries and promoters

Cohesin is best known for its role in loop extrusion, while nucleosome phasing at regulatory elements is usually attributed to local DNA-bound factors and remodelers. Here we identify a previously unrecognized role for cohesin-mediated extrusion in maintaining local nucleosome architecture at CTCF sites and transcription start sites. Using single-molecule nano-NOMe-seq during SCC1 depletion, cell-cycle progression and Sororin perturbation, we show that CTCF-bound sites contain distinct nucleosome architectures ranging from ordered CTCF-footprinted arrays to footprint-free nucleosomal and inaccessible configurations.. In unperturbed cells, ordered CTCF-footprinted nucleosome arrays were strongest at a boundary-enriched class of CTCF sites without regulatory elements. By contrast, CTCF sites overlapping regulatory elements showed stronger aggregate CTCF ChIP-seq signal despite weaker footprinting and less regular nucleosome phasing, indicating that boundary-like nucleosome architecture is not predicted by CTCF occupancy alone. At TSSs, promoter-proximal CTCF defined a distinct state balance: CTCF-positive promoters were enriched for accessible and footprinted configurations, whereas CTCF-negative promoters showed proportionately fewer footprinted states and were dominated by footprint-free phased arrays. Acute SCC1 depletion disrupted nucleosome organization at CTCF sites without regulatory elements and at promoters with promoter-proximal CTCF, despite retention of aggregate CTCF ChIP-seq signal at CTCF-bound sites. SCC1 depletion also altered nucleosome organization at promoters lacking promoter-proximal CTCF, highlighting that cohesin-dependent nucleosome patterning is not simply a CTCF-barrier phenomenon. Cell-cycle and Sororin analyses further separated extrusion-associated states from Sororin-stabilized post-replicative cohesin, highlighting that nucleosome order depends on effective cohesin-barrier encounters rather than cohesin occupancy alone. Together, these findings establish cohesin collisions as an active local mechanism that patterns nucleosomes at boundaries and promoters.

molecular biology↗

bioRxiv2026

BioGAIP: A Scalable, User-Friendly and Robust LLM-Powered Multi-Agent System for Automated Bioinformatics Tasks

The rapid explosion of large-scale, high-throughput biological data has created an urgent demand for efficient analysis pipelines. Traditional bioinformatics approaches, while powerful, often require specialized computational expertise, placing them out of reach for bench biologists. Large Language Models (LLMs) offer new possibilities for automating complex reasoning and tool integration, yet existing LLM-based solutions have not sufficiently lowered this barrier, and expert-level analysis remains inaccessible to most nonexperts. Here, we present BioGAIP, an LLM-powered agent that integrates expert-level reasoning within an end-to-end platform for bioinformatics tasks. By coupling optimized autonomous agents with full graphical interfaces, BioGAIP transforms complex analytical workflows into an automated, user-friendly, and low-intervention process with natural language input. Key features of BioGAIP include dynamic information retrieval, automatic environment configuration, and self-directed design of analysis pipelines, making large-scale multi-omics analysis highly accessible. Built on agent-based client-server architecture, BioGAIP ensures secure resource management and supports heavy computational demands. Extensive evaluations on diverse published datasets demonstrate that BioGAIP reliably recapitulates established biological insights and shows strong potential for novel discovery. By democratizing complex bioinformatics workflows, BioGAIP accelerates accessible data-driven discovery for both experts and nonexperts.

bioinformatics↗

bioRxiv2026

The ENL-USP7 Complex Regulates HIV Latency Through BRD4 Stabilization

HIV-1 persists in CD4 T cells and brain microglia through host factors that enforce viral latency, yet the mechanisms that stabilize key transcriptional regulators remain incompletely understood. Here, we identify the YEATS domain-containing protein ENL and its associated deubiquitinase USP7 as a host complex that maintains HIV-1 latency. USP7 stabilizes BRD4 by deubiquitination, suppressing HIV transcription and sustaining viral quiescence. Disruption of the ENL-USP7 complex using selective PROTACs reactivates latent HIV in cell line models, as well as in resting CD4 T cells and microglia isolated from people with HIV on antiretroviral therapy. These findings uncover a critical ENL-USP7-BRD4 axis that enforces HIV-1 latency and highlight USP7 as a potential target for latency-reversing strategies. HighlightsO_LIENL, a YEATS domain-containing crotonylation reader, acts as a suppressor rather than an activator of HIV-1 transcription. C_LIO_LIENL recruits USP7 to stabilize BRD4 and enforce viral latency. C_LIO_LIDisruption of the ENL-USP7-BRD4 axis reactivates latent HIV in T cells and microglia. C_LIO_LITargeting USP7 or ENL reveals a therapeutic vulnerability in HIV reservoirs. C_LI

microbiology↗

bioRxiv2026

Long-read metagenomic sequencing reveals novel lineages and functional diversity in urban soil microbiome

City parks and other urban green spaces can bring significant benefits to the physical and mental health of city residents. However, there is limited knowledge about the microbial communities inhabiting these urban soils. Here, we applied long-read metagenomic sequencing to 58 urban soil samples from two major cities in China, enabling genome-resolved reconstruction of microbial diversity at unprecedented contiguity. We recovered 7,949 medium- and high-quality metagenome-assembled genomes, comprising 4,171 species-level genome bins, of which over 97% represent previously undescribed species. Long-read assemblies revealed extensive secondary metabolic capacity, including more than 30,000 biosynthetic gene clusters, which were highly contiguous compared with those from fragmented short-read assemblies. Beyond secondary metabolism, we uncovered over 2 million small protein families, including hundreds that are strongly enriched in the neighbourhood of defense systems and mobile genetic elements, highlighting their overlooked role in urban soils. These findings expand our understanding of the functional diversity of urban soil microbiomes and provide new insights with implications for urban public health.

bioinformatics↗

bioRxiv2026

The RNA Editome of Esophageal Squamous Cell Carcinoma Identifies an ADAR1-CDK13 Editing Feedback Loop Mediating cGAS-STING Activation in Early Tumorigenesis

ObjectiveRNA adenosine-to-inosine (A-to-I) editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a pervasive post-transcriptional mechanism that expands transcriptomic and proteomic diversity. However, the global landscape of RNA A-to-I editing, as well as its functional and clinical significance in esophageal squamous cell carcinoma (ESCC), remains largely unexplored. This study aimed to systematically characterize the RNA editome of ESCC and elucidate its biological and clinical significance. MethodsWhole-transcriptome sequencing was performed on 121 primary ESCC tumors, with or without lymph node metastasis, together with matched normal tissues, to construct a high-resolution RNA editome. ADAR1-regulated RNA editing events were identified, and their functional consequences were investigated using integrated transcriptomic, phosphoproteomic, and RNA immunoprecipitation sequencing (RIP-seq) analyses. Associations between CDK13 editing, cGAS-STING-interferon-stimulated gene (ISG) signaling, and patient survival were further evaluated. ResultsA total of 222,020 high-confidence RNA editing sites were identified, of which approximately 98% were A-to-I events, including 124,486 ESCC-specific edits predominantly enriched in introns, 3' untranslated regions, and non-coding RNAs, highlighting a pervasive post-transcriptional regulatory layer. RNA A-to-I editing was extensively remodeled and globally up-regulated in non-metastatic ESCC, whereas only minimal changes were observed during lymph node metastasis, indicating that RNA editing alterations predominantly occur during early tumorigenesis. CDK13 emerged as a recurrent ADAR1 target, with RNA editing inversely correlated with CDK13 expression. ADAR1-mediated CDK13 editing established a positive feedback loop associated with enhanced interferon-stimulated gene (ISG) signaling and poorer survival in non-metastatic ESCC. Mechanistically, partial attenuation of CDK13 induced chronic, tumor cell-intrinsic activation of the cGAS-STING-ISG pathway. Integrated multi-omics analyses further revealed that CDK13 regulates phosphorylation networks governing cytoskeleton organization, intracellular trafficking, RNA homeostasis, and immune signaling. ConclusionRNA A-to-I editing represents a dynamic regulatory mechanism driving early ESCC progression and remodeling tumor cell-intrinsic immune signaling. ADAR1-mediated editing of CDK13 provides a mechanistic link between RNA editing and cGAS-STING-ISG pathway activation, revealing potential therapeutic vulnerabilities and supporting its utility as an early prognostic biomarker in ESCC.

cancer biology↗

bioRxiv2025

LorMe: a streamlined and interoperable R framework for end-to-end microbiome analysis

Microbiome research is rapidly evolving accompanied by increasingly diverse analytical strategies and visualization formats. However, existing R-based tools remain fragmented, differ in data structures, and often require extensive package-specific pre-processing. This increases command-line complexity and limits both interoperability and reproducibility across packages. Here, we present LorMe (Lightweight One-line Resolving Microbial Ecology), an R package that provides a unified, interoperable, and user-friendly framework for microbiome data analysis. LorMe incorporates a standardized S4 object system with fully bidirectional compatibility with phyloseq and microeco, which enables seamless data exchange across major microbial analysis packages. A global configuration system ensures consistent parameter control and visualization standards, and a modular architecture supports both complete end-to-end workflows and flexible execution of individual analytical components. Based on these, LorMe further offers an one-command pipeline that conducts the full spectrum of microbial community analyses, including alpha and beta diversity, differential abundance testing, co-occurrence network inference, and meta-network construction, while archiving all intermediate objects and source data to ensure complete reproducibility. Demonstrations using sample datasets show that LorMe performs comprehensive analyses within minute, produces publication-ready outputs, and maintains methodological transparency. Application to a real rhizosphere dataset revealed biologically coherent patterns across diversity metrics, differential taxa, and network modules, highlighting the capacity of LorMe to support robust ecological interpretation. Collectively, LorMe provides a lightweight, extensible, and flexible solution that reduces technical barriers and enhances reproducibility in microbiome research. LorMe package is freely accessible from both CRAN (https://cran.r-project.org/web/packages/LorMe) and github (https://github.com/wangnq111/LorMe)

bioinformatics↗

bioRxiv2025

Pharmaceuticals residues lead to enrichment of Human, Animal, and Plant Pathogens in Wastewater

Wastewater forms a reservoir for diverse microbial pathogens, posing significant risks to public health and aquatic ecosystems. They further contain several pharmaceutical residues that can induce profound shifts in the wastewater microbiome. In this study, we assessed whether common non-antimicrobial pharmaceuticals such as pain killers and blood pressure regulators impact wastewater pathogen profiles. We spiked wastewater with caffeine (stimulant), atenolol (beta-blocker), paracetamol (analgesic), ibuprofen (anti-inflammatory) and enalapril (ACE-inhibitor), and monitored microbiome 16S rRNA gene profiles. We then matched species composition to a comprehensive database of human, animal, and plant pathogens. All pharmaceuticals significatively increased abundance and biodiversity for zoonotic, plant, and animal pathogens. These findings highlight that pharmaceutical contamination poses a biohazard risk by fostering pathogen growth. We call for a paired, continuous monitoring of chemical and biological pollutants and a more stringent removal of pharmaceutical residues from wastewater.

microbiology↗

bioRxiv2025

Using the simple telegraph model to decipher transcriptional burst regulation across genome-wide data

Gene transcription is a stochastic bursting process, with burst frequency and burst size as core parameters. Deciphering its genome-wide regulation is challenging, as complex models (capturing detailed biology) are impractical for large-scale use due to unstable inference and high computation. We proposed a simple telegraph model-based framework to analyze genome-wide scRNA-seq and smFISH datasets, addressing these limitations. When sample size [≥] 500 and burst parameter change [≥] 3-fold, its inferred burst frequency- and size-dominated variations reliably proxy true regulation. Analyses across mouse cells (CAST/C57 alleles, fibroblasts vs. embryonic stem cells) and healthy/hypertrophic cardiomyopathy (HCM) human heart tissues revealed key rules: 1) Burst frequency- or size-dominated regulation was primary (over 70% of variable genes), with more bursty-regulated genes in HCM; 2) TATA-initiator synergy (enhancing burst size-dominated regulation) was lost in HCM; 3) Burst frequency-dominated genes enriched in genome stability/cell cycle/apoptosis (via TFs like Foxo4/Mcm2), while burst size-dominated ones in signaling/metabolism/proteostasis (via TFs like Zfp322a/Smchd1/Ppargc1a), and their interdependent dysregulation accelerated HCM. This study establishes the simple telegraph model as a scalable framework linking transcriptional burst dynamics to cell fate and pathology.

molecular biology↗

bioRxiv2025

No more than three PlpE non-overlapping epitopes trigger significant antibody production in individuals vaccinated with the Pasteurella multocida epitope-chimeric proteins

Current vaccine research still confronts multiple challenges, and epitope-focused vaccine design serves as an effective technical approach to address these issues. Antigens harbor multiple epitopes; however, the number of epitopes capable of triggering significant antibody responses in vaccinated individuals remains undefined. This study aimed to determine the number of non-overlapping epitopes--designated "effective epitopes" hereafter--that trigger significant antibody production in vaccinated individuals when presented in distinct PlpE epitope-chimeric proteins. Herein, chimeric proteins incorporating varying numbers of PlpE non-overlapping B-cell epitopes were generated. By analyzing serum antibody responses in vaccinated individuals, the number characteristic of PlpE effective epitopes was elucidated. The total number of PlpE effective epitopes in vaccinated individuals was 2.6 (95%CI: 1.909-3.201) for full-length PlpE, and 1.2 (95%CI: 0.5426-1.857), 0.9 (95%CI: 0-1.820), and 0.2 (95%CI: 0-0.5016) for the PlpE chimeric proteins (PlpE-VP60P, PlpE-BcfA, PlpE-PtfA), respectively. With an increase in the number of PlpE non-overlapping epitopes incorporated into the chimeric proteins, the number of PlpE effective epitopes exhibited a trend of initial increase followed by a decrease. Ultimately, the average total number of effective epitopes across all PlpE chimeric proteins did not exceed 3, with the highest number 2.1 (95%CI: 1.572-2.628). In conclusion, the number of PlpE non-overlapping epitopes on an antigen, that trigger significant antibody responses in each vaccinated individual, is very limited. IMPORTANCEEpitopes underpin the antigenicity of protein antigens. Although the concept of antigenic epitopes has been proposed over 50 years, our understanding on epitopes remains incomplete. Multiple antigenic epitopes can be identified on a single antigen, while the number of these epitopes that function in vaccinated individuals remains unclear--a gap hindering the rational design of vaccines. In previous studies, we identified 6 non-overlapping epitopes of Pasteurella multocida PlpE. Herein, we found that the total number of non-overlapping epitopes--capable of significantly triggering antibody production--that are present in PlpE chimeric proteins does not exceed 3 per vaccinated individual. This finding offers important insights for rational vaccine design: given the highly limited number of non-overlapping epitopes that function in vaccinated individuals, only a limited number of epitopes can be grafted onto scaffold proteins. Epitope-focused vaccine design must therefore account for competitive interactions between epitopes on the new antigen.

immunology↗

bioRxiv2025

Multi-omics reveals lipid metabolism, mitochondrial and extracellular matrix dysregulation of diabetic cardiomyopathy in the human heart

Diabetic cardiomyopathy (DbCM) is a condition characterized by myocardial dysfunction in diabetes. Although the clinical recognition of DbCM is increasing, its underlying molecular mechanisms remain poorly understood. We aimed to conduct a comprehensive multi-omics analysis of heart tissue from cardiomyopathy patients (both with and without diabetes),alongside tissue from healthy donors, by integrating transcriptomic, 4D-DIA proteomic, and full-spectrum widely targeted metabolomic data. Differential analyses revealed a significant metabolic pattern in patients with DbCM, characterized by increasing utilization of triglyceride-derived fatty acids. Correlation analyses highlighted impaired BNIP3L-mediated mitophagy as a potential contributor to the disruption of fatty acid metabolism and mitochondrial dysfunction in DbCM. Protein interaction and fibrotic trichrome analyses showed that patients with DbCM had impaired cardiac matrix repair compared to patients with cardiomyopathy without diabetes. These findings provide a system-level understanding of DbCM and reveal molecular signatures driving its progression, offering insights for targeted therapeutic strategies against diabetic heart disease.

bioinformatics↗

bioRxiv2025

Attomolar Detection of HIV-1 with Label-Free RCA-rCRISPR on Smartphone

Human Immunodeficiency Virus-1 (HIV) remains a major global public health challenge, having led to over 42.3 million deaths since its discovery in the early 1980s. Despite progress in prevention and treatment, around 60% of people with HIV (PWH) remain undiagnosed in resource-limited regions, disproportionately affecting vulnerable populations and underserved communities across the world. This illustrates the critical need for accessible, accurate, and equipment-free diagnostic tools to enhance detection and thus provide opportunities to curb its spread. Here, we developed a low-cost, robust, and label-free rolling circle amplification (RCA)-rCRISPR diagnostic platform for detecting HIV viral load with minimal instrumentation. Our strategy, combining the integration of RNA-detecting RCA reaction with plasmid reporter-based ratiometric CRISPR (rCRISPR), enables sensitive detection of unprocessed RNA targets without the need for intensive sample pre-treatment. This label-free RCA-rCRISPR diagnostic platform detected HIV RNA down to single-digit aM sensitivity (~3000 copies/mL) from PWH-derived HIV samples ex vivo. Unlike typical RCA, which requires sample fragmentations to break long RNA target sequences, our design harnesses the triple functions of the phi29 DNA polymerase (namely exonuclease activity, polymerization, and strand displacement), enabling the detection of the entire HIV genome without pre-fragmentation. For point-of-care (POC) applications, we constructed an all-in-one smartphone-based minigel electrophoresis device to facilitate equipment-free HIV viral load testing, making it accessible to resource-limited communities. Additionally, the assay has demonstrated the ability for point mutation detection (BRAF mutation in canine urothelial carcinoma), showcasing the robustness of our strategy for broad disease diagnostic applications.

bioengineering↗

bioRxiv2025

Sustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation

Cancer cachexia is an involuntary weight loss condition characterized by systemic metabolic disorder. A comprehensive flux characterization of this condition however is lacking. Here, we systematically isotope traced eight major circulating nutrients in mice bearing cachectic C26 tumors (cxC26) and food intake-matched mice bearing non-cachectic C26 tumors (ncxC26). We found no difference in whole-body lipolysis and proteolysis, ketogenesis, or fatty acid and ketone oxidation by tissues between the two groups. In contrast, compared to ncxC26 mice ad libitum, glucose turnover flux decreased in food intake-controlled ncxC26 mice but not in cxC26 mice. Similarly, sustained glucose turnover flux was observed in two autochthonous cancer cachexia models despite reduced food intake. We identified glutamine and alanine as responsible for sustained glucose production and tissues with altered use of glucose and lactate in cxC26 mice. We provide a comprehensive view of metabolic alterations in cancer cachexia revealing those distinct from decreased nutrient intake. HighlightsO_LIQuantitative fluxomics of cancer cachexia under matched food intake and body weight C_LIO_LIIntact lipolysis, proteolysis, ketogenesis, and lipid oxidation in cachectic mice C_LIO_LISustained glucose consumption in cachectic mice despite reduced food intake C_LIO_LIIncreased glucose production from glutamine and alanine in cachectic mice C_LI

cancer 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↗