Biology subjects

Qi, B.

Publications and source records attributed to Qi, B..

17 recordsLinked to original sources

bioRxiv2026

Bacterial Peptidoglycan Extends Lifespan by Activating Lysosomal Activity through V-ATPase Binding

Lysosomal dysfunction is a hallmark of aging, yet whether microbial components actively regulate this organelle to influence longevity remains unknown. Here, we identify bacterial peptidoglycan (PGN), a major cell wall component degraded by host lysozyme, as an evolutionarily conserved activator of lysosomal function that extends lifespan in both C. elegans and mice. We show that aging leads to an intestinal decline in lysozyme expression, which impairs bacterial cell-wall digestion and results in systemic PGN deficiency. Late-life PGN supplementation (starting at 18 months of age) significantly prolongs mouse lifespan and improves healthspan. Mechanistically, PGN localizes to lysosomes and directly binds V-ATPase subunits, enhancing ATP hydrolysis activity and promoting lysosomal acidification. This effect is abolished by V-ATPase inhibition (bafilomycin A1) or genetic disruption of lysosomal components (cup-5 and vha-12 mutants), confirming that functional V-ATPase is strictly required for lysosomal function and the longevity benefit. Importantly, PGN restores lysosomal acidification in aged cells, alleviates cellular senescence markers, and improves multiple hallmarks of aging including locomotion and muscle integrity. Collectively, these findings reveal an evolutionarily conserved mechanism whereby hosts exploit bacterial cell wall components to maintain cellular homeostasis, establishing a gut microbiome-lysosome-longevity axis with implications for microbiome-based anti-aging interventions.

physiology↗

bioRxiv2026

ADSS1 is a suppressed metabolic control node in dystrophic skeletal muscle

Duchenne muscular dystrophy is initiated by dystrophin loss but is accompanied by profound metabolic remodelling. Here, we identify suppression of the muscle-enriched adenylosuccinate synthase, ADSS1, and the purine nucleotide cycle in mdx muscle. Integrated multi-omic profiling revealed a compensated purine-stress state in which nucleotide salvage and quality control were increased to preserve adenine nucleotide abundance and buffer consequential toxic/disruptive deoxy-/nucleotide production. Purine metabolism was the highest-impact joint pathway with metabolite and transcript hits in mdx muscle, and its maintenance program was directionally conserved in human ADSS1 myopathy. Interventions positioned around ADSS1 separated the outputs of this node. Ribose and dimethyl fumarate remodelled upstream or downstream stress programs, whereas only adenylosuccinic acid bypassed ADSS1 to expand the adenine nucleotide pool and remodel CoA/acetyl-CoA metabolism. All three interventions suppressed pro-adipogenic transcription without broadly correcting the lipidome. These findings identify ADSS1 as a regulated metabolic control node that couples purine retention to inflammatory and adipogenic remodelling in dystrophic muscle.

molecular biology↗

bioRxiv2026

Single-Cell Multi-Omics Dissection of Malignant Evolutionary Mechanisms and Construction of a Prognostic Model for Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) exhibits pronounced heterogeneity across WHO histological grades, yet systematic single-cell multi-omics studies characterizing these transitions remain limited. We integrated scRNA-seq and scATAC-seq data across ccRCC WHO grades to establish a multi-omics framework encompassing tumor cells and immune populations. Using pseudotime trajectory analysis and machine learning ensembles, we developed a prognostic signature (CBG) from core nodes of transcriptional regulatory networks. We found that in tumor cells, epigenetic alterations consistently precede metabolic reprogramming and invasive adaptation. CD8+ T cell exhaustion followed a trajectory shifting from IRF7- to ZNF683-regulated states, while monocytes differentiated toward M1 and M2 macrophages orchestrated by NFIC/IL1B and CEBPD/GLI2. Intercellular communication networks showed a temporal progression from inflammation, through vascular remodeling, to immunosuppression dominance. The CBG signature demonstrated robust performance in independent cohorts, identifying SLC11A1 and SH3YL1 as antagonistic survival determinants. This study elucidates the dynamic molecular and immunological mechanisms underlying ccRCC grade progression, providing a robust framework for subtype-specific prognostication and precision therapeutic targeting.

bioinformatics↗

bioRxiv2026

Phylogenetically Dispersed Subsetting for Species-Level Machine Learning Evaluation: Dependence-Aware Validation and Limited Effective Information

Species are widely treated as independent sampling units in comparative analyses, yet shared evolutionary history induces structured dependence that can substantially reduce the amount of independent information available for statistical evaluation and inference. This mismatch between nominal species richness and effective information content can lead to overestimation of statistical precision in species-level analyses. Here, we develop a general framework for quantifying effective information under phylogenetic dependence. We define evaluation subsets embedded within a shared phylogenetic covariance structure and introduce two complementary measures. The first, MIESS (mean-based independence-equivalent sample size), quantifies the amount of independent information available for estimating aggregate quantities under a specified phylogenetic correlation structure, derived from generalized least-squares variance principles. The second, PIESS (prediction-metric-based independence-equivalent sample size), extends this idea to predictive evaluation by mapping uncertainty in standard performance metrics (RMSE, MAE, and R{superscript 2}) onto an independence-equivalent sample size scale via calibration against independent-sample benchmarks. We evaluate this framework using empirical mammalian phylogenies (Cricetidae) and idealized tree topologies representing contrasting phylogenetic structures. Across these systems, and under standard models of trait evolution including Brownian motion (BM), Ornstein-Uhlenbeck (OU), and Early-Burst (EB) processes, we compare subsets constructed under phylogenetically dispersed, clustered, and random sampling schemes. Across all settings, dispersed subsets reduce redundancy relative to clustered subsets but do not eliminate dependence-induced information loss. For example, under the{lambda} -transformed BM analysis, the dispersed 64-species subset yielded R{superscript 2}-based PIESS values well below the nominal size under moderate to strong phylogenetic signal (14.59 at{lambda} = 1.00, increasing to 31.96 at {lambda} = 0.50). The resulting loss arises from residual phylogenetic covariance and is robust across evolutionary regimes and sampling fractions. These results indicate that nominal species counts can substantially overestimate independent information in species-level evaluation contexts, and that accounting for phylogenetic dependence is essential for interpreting statistical precision, comparing predictive performance, and designing evaluation protocols in comparative biological analyses.

evolutionary biology↗

bioRxiv2025

Adaptive Feature-Weighted Stacking Ensemble for Short-Term Risk Prediction of Prolonged Length of Stay in Elderly Trauma Patients

The Adaptive Feature-Weighted Stacking Ensemble (AFWSE) model is presented here as a new machine learning method that provides staged prediction of prolonged length of stay in trauma patients. We used a retrospective dataset of elderly trauma patients using simulated data from publicly available feature characteristics. AFWSE is designed to combine different base learners like logistic regression, random forest, and gradient boosting, into a stacked ensemble with an adaptive feature weighting mechanism that allows researchers to identify complex patterns while emphasizing clinically relevant features. The AFWSE model was compared to standard machine learning methods, specifically, logistic regression, random forest, gradient boosting, and neural networks, demonstrating consistently better predictive validity and accuracy. The AFWSE identified important features which included older age, injury site, injury mechanism, or type of trauma, and Glasgow Coma Scale, which contributes to the existing body of clinical evidence. The AFWSE model mechanism and its potential clinical interpretation and implications are discussed, along with addressing the recognized limitations of using simulated datasets.

bioengineering↗

bioRxiv2024

FvM4K1, a Serine/Threonine Kinase and Ste20 Homolog Positively Regulates Fruit Size via Hippo Signalling Pathway in Woodland Strawberry (Fragaria vesca)

Strawberry fruit size is critical for its marketability. However, organ size control is a complex process regulated by various signaling pathways. In animals, the Hippo signaling pathway acts as a negative regulator of organ size, with Ste20 kinase, a serine/threonine kinase being a key component. Mutation in Ste20 causes excessive cell proliferation and enlarged organs. In this study, FvM4K1, a Ste20-like kinase from woodland strawberry (Fragaria vesca), is identified. FvM4K1 partially restores defects in a yeast Ste20 mutant ste20{Delta} and fully rescues growth in Arabidopsis mutant atsik1-4 lacking its Ste20 homolog, AtSIK1, underscoring its functional conservation. Downregulation FvM4K1 by RNAi in woodland strawberry leads to fruits and smaller plants resulting from reduced cell size and number, while overexpression increases organ size, indicating a positive role in fruit and organ size control which contrasts the negative role of Ste20 in other organisms. FvM4K1 auto-phosphorylates, with Lys269 and Thr396 being critical for its function. FvM4K1 interacts with FvMOB1A and FvMOB1B, components of the Hippo signalling pathway, and phosphorylates them at Thr35 and Thr36, respectively. These findings provide novel insights into the mechanisms underlying fruit and organ size control in woodland strawberry and contribute to our understanding of the Hippo signalling pathway in higher plants, a pathway that remains largely unexplored. It also opens new avenues for exploring the regulatory function of Hippo pathway in plant development and potentially inform biotechnological strategies for crop improvement.

plant biology↗

bioRxiv2024

Neuronal Detection Triggers Systemic Digestive Shutdown in Response to Adverse Food Sources

The ability to sense and adapt to adverse food conditions is essential for survival across species, but the detailed mechanisms of neuron-digestive crosstalk in food sensing and adaptation remain poorly understood. This study identifies a novel mechanism by which animals detect unfavorable food sources through neurons and initiate a systemic response to shut down digestion, thus safeguarding against potential harm. Specifically, we demonstrate that NSY-1, expressed in AWC neurons, detects Staphylococcus saprophyticus (SS) as an unfavorable food source, prompting the animal to avoid and halt digestion of SS. Upon detection, the animals activate the AWCOFF neural circuit, leading to a systemic digestive shutdown, which is mediated by NSY-1-dependent STR-130. Additionally, NSY-1 mutation triggers the production of insulin peptides, including INS-23, which interact with the DAF-2 receptor to modulate SS digestion and affects the expression of intestinal BCF-1. These findings uncover a crucial survival strategy through neuron-digestive crosstalk, where the NSY-1 pathway in AWC neurons orchestrates food evaluation and initiates digestive shutdown to adapt effectively to harmful food sources.

physiology↗

bioRxiv2024

Moderate-term dimethyl fumarate treatment reduces pathology of dystrophic skeletal and cardiac muscle in a mouse model

In Duchenne muscular dystrophy (DMD), corticosteroids significantly slow disease progression and have been used as a standard of care tool for more than 30 years. However, corticosteroids also impart side effects severe enough to preclude use in some patients. There remains an unmet need for new therapeutics that target the flow-on pathogenic mechanisms of DMD with a more favourable side-effect profile. We have previously demonstrated that short-term treatment with dual-purpose anti-inflammatory, anti-oxidative dimethyl fumarate (DMF), a drug with indication and established safety data in Multiple Sclerosis, more selectively modulates Duchenne (mdx) immunology than the frequently used corticosteroid, prednisone (PRED). Here, we assess the effect of moderate-term DMF treatment over 5 weeks in the typically mild mdx mouse model that we aggravated using exercise. We show that like PRED, DMF maintains anti-inflammatory action but with additional anti-fibrotic and anti-lipogenic effects on muscle with moderate-term use. This study supports our previous work highlighting DMF as a possible repurposing candidate for DMD, especially for patients who cannot tolerate chronic corticosteroid treatment.

pathology↗

bioRxiv2024

A Novel Role of Hyaluronan and its Membrane Receptors, CD44 and RHAMM in Obesity-Related Glomerulopathy

Obesity-related glomerulopathy (ORG) contributes to diabetic nephropathy and kidney cancer, leading to chronic/end-stage kidney disease. To date, treatments for ORG are limited because of incomplete understanding of the disease pathogenesis. Here, we identified a novel role for hyaluronan (HA) and its membrane receptors, CD44 and RHAMM in obesity-associated renal inflammation, fibrosis, tubular injury, and kidney dysfunction. Pharmacological and genetic ablation of HA, CD44 or RHAMM reversed these renal disorders induced by high fat diet feeding in mice in vivo. Increased HA content, and CD44 and RHAMM expression damaged the kidney via activation of TGF-{beta}1/Smad2/3, P38/JNK MAPK and ROCK/ERK pathways. We further established a link between renal insulin resistance and ECM remodelling using human kidney cells in vitro, shedding mechanistic insight into the role of HA, CD44 and RHAMM in the pathogenesis of ORG. Furthermore, in human kidney biopsies gene expression of CD44 and RHAMM was increased in chronic kidney disease and diabetic nephropathy, and their levels were correlated with markers of kidney (dys)function (GFR, serum creatinine, proteinuria). Our findings provide evidence for HA-CD44/RHAMM as a potential therapeutic target in ORG and consequent prevention of chronic kidney disease.

physiology↗

bioRxiv2024

Host-pathogen Coadaptation by running with PAR protein

Host-pathogen coadaptation is mutually beneficial for the survival of both organisms. Embryo development is a crucial aspect of animal evolution as it ensures the continuation of their offspring. However, there is little understanding of the coadaptation mechanisms underlying embryo developmental factors in host-pathogen interactions. Here, by using a C. elegans-P. aeruginosa infection model, we demonstrate that PAR-5, essential for the establishment of anterior-posterior polarity within the single cell C. elegans zygote, acts as a mediator in regulating host-pathogen co-evolution. We discover that Pseudomonas aeruginosa-PA14 infection induces PAR-5 expression, which accelerates animal embryo development and ensures the continuity of their offspring. Moreover, PA14 stimulates host PAR-5 secretion, which reduces the virulence of PA14. Both functions of PAR-5 are beneficial for host survival. Meanwhile, pathogens utilize PAR-5 to inhibit host immunity/UPRER by bypassing the core PMK-1-mediated innate immunity and activating mTOR by interacting with LET-363, promoting pathogen spread. Therefore, our study uncovers an unexpected mechanism in host-pathogen co-evolution that targets a host embryo developmental factor, promoting coexistence and facilitating the adaptation of both hosts and pathogens.

evolutionary biology↗

bioRxiv2023

Use of dye sensitizers for increased photoacoustic mechanosensation

The photoacoustic effect refers to the generation of pressure waves in matter stimulated by light[1]. In the context of radiology (i.e., photoacoustic imaging) waves generated by pulsed laser light are detected by an ultrasound transducer[2-4]. It has been shown that photoacoustic waves produce a mechanical, tactile sensation in humans on bare skin[5]. In a series of psychophysical experiments, performed with both medical grade and off-the-shelf pulsed light systems, participants could detect, categorically describe, and discern the direction of travel of pulsed optical stimuli with the use of a dye as an optical absorber on the skin. To a large extent, the sensations were perceived as localized vibration on the glabrous surface of the fingers, when sensitized with the thin film of dye. This form of sensory stimulation demonstrates an enhanced non-contact, non-optogenetic, in situ activation of the mechanosensory system. This modality of sensation may provide a tool that leads to new insights in psychology, neuroscience, mechanobiology, and the health sciences. Finally, it has many advantageous characteristics for human interaction with artificial environments, as optical signals can be projected onto the skin across distances.

neuroscience↗

bioRxiv2023

UPRER-immunity axis acts as physiological food evaluation system that promotes aversion behavior in sensing low-quality food

To survive in challenging environments, animals must develop a system to assess food quality and adjust their feeding behavior accordingly. However, the mechanisms that regulate this chronic physiological food evaluation system, which monitors specific nutrients from ingested food and influences food-response behavior, are still not fully understood. Here, we established a low-quality food evaluation assay system and found that heat-killed E. coli (HK-E. coli), a low sugar food, triggers cellular UPRER and immune response. This encourages animals to avoid low-quality food. The physiological system for evaluating low-quality food depends on the UPRER (IRE-1/XBP-1) - Innate immunity (PMK-1/p38 MAPK) axis, particularly its neuronal function, which subsequently regulates feeding behaviors. Moreover, animals can adapt to a low-quality food environment through sugar supplementation, which inhibits the UPRER -PMK-1 regulated stress response by increasing vitamin C biosynthesis. This study reveals the role of the cellular stress response pathway as physiological food evaluation system for assessing nutritional deficiencies in food, thereby enhancing survival in natural environments.

developmental biology↗

bioRxiv2023

Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer

The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate (DSS). By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC{Delta}Chil1 mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a "scaffold model" for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.

microbiology↗

bioRxiv2022

Characterization of a miniaturized ultrasound transducer customized for oral health applications

ObjectiveTo customize a miniaturized ultrasound transducer to access full-mouth B-mode, color Doppler and spectral Doppler imaging for monitoring oral health. MethodsA customized periodontal ultrasound transducer SS-19-128 (19 MHz, 128 channels) with 1.8 cm wide and 1 cm thick was developed and connected to a data acquisition (DAQ) system. B-mode, color Doppler, and spectral Doppler data could all be collected with SS-19-128. The imaging resolution and penetration capacity of SS-19-128 were characterized on phantoms. Five human subjects were recruited to demonstrate B-mode and Doppler imaging by SS-19-128. Gingival thickness was measured on 11 swine teeth by SS-19-128 for comparison to conventional transgingival probing via Bland-Altman analysis and Pearson correlation. ResultsThe axial and lateral spatial resolution at 5.5 mm depth is 102.1 m and 142.9 m, respectively. The penetration depth in a tissue-mimicking phantom is over 30 mm. In vivo B-mode imaging of all 28 teeth was demonstrated on one human subject, and imaging of tooth #18 was accessed on five human subjects. Gingival thickness measurement compared with transgingival probing showed a bias of -0.015 mm and SD of 0.031 mm, and a r = 0.9235 (P<0.0001) correlation. In vivo color and spectral Doppler imaging of the supraperiosteal artery in human gingiva was performed to generate hemodynamic information. ConclusionsThe small size of SS-19-128 offers important advantages over existing technology--more specifically, whole-mouth scanning/charting reminiscent of radiography. This is nearly a two-fold increase in the number of teeth that can be assessed versus existing transducers.

bioengineering↗

bioRxiv2022

Full-mouth photoacoustic/ultrasound imaging of the periodontal pocket with a compact intraoral transducer

Periodontitis is a public issue and imaging periodontal pocket is important to evaluate periodontitis. Regular linear transducers have limitations in imaging the posterior teeth due to their geometry restrictions. Here we characterized a transducer that can image the entire human mouth including assessment of periodontal pockets via a combination of photoacoustic and ultrasound imaging. Unlike conventional transducer design, this device has a toothbrush-shaped form factor with a side-view transducer to image molars (total size: 1 x 1.9 cm). A laser diode was integrated as the light source to reduce the cost and size and facilitates clinical transition. The in vivo imaging of a molar of a periodontal patient demonstrated that the transducer could image in the posterior area of gum in vivo; the value determined by imaging was within 7% of the value measured clinically.

bioengineering↗

bioRxiv2021

BREVIPEDICELLUS and ERECTA mediate expression of AtPRX17 in preventing Arabidopsis callus retardation and browning

Efficient in vitro callus generation is fundamental to tissue culture propagation, a process required for plant regeneration and transgenic breeding for desired phenotypes. Identifying genes and regulatory elements that prevent callus retardation and browning is essential to facilitate the development of vitro callus systems. Here we show that BREVIPEDICELLUS (BP) and ERECTA (ER) pathways in Arabidopsis callus are converged to prevent callus browning and positively regulate an isoperoxidase gene AtPRX17 expression in the rapid growth callus. Loss of functions in both BP and ER resulted in markedly increasing callus browning. Transgenic lines with pro35S::AtPRX17 in the bp-5 er105 double mutant background fully rescued this phenotypic abnormality. Using plant in vitro DNA-binding assays, we observed that BP protein bound directly to the upstream sequence of AtPRX17 to promote its transcription during callus growth. ER is a universally presenting factor required for cell proliferation and growth, we show that ER positively regulates expression of a transcription factor WRKY6, which also directly binds to an additional site of the AtPRX17 promoter for its high expression. Our data reveals an important molecular mechanism in regulating expression of peroxidase isozyme to reduce Arabidopsis callus browning. HighlightBREVIPEDICELLUS and ERECTA are involved in regulating Arabidopsis callus browning by controlling expression of AtPRX17.

plant biology↗

bioRxiv2018

Microbial Community Structure and Diversity of Shrimp Paste at Different Fermentation Stages

High-throughput sequencing was used to reveal the highly diverse bacterial populations in shrimp paste at different fermentation stages. We studied three stages of fermentation and obtained 448,916 reads. Using this approach, we revealed the presence of 30 phyla, 55 classes, 86 orders, 206 families and 695 genera of bacteria in the shrimp paste. Shrimp paste in fermentation metaphase had a more diverse microbiota than that in fermentation prophase and fermentation anaphase. Diversity appeared greatest in fermentation anaphase. The four dominant phyla were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. The most common genera were Psychrobacter, Halomonas, Bacillus, Alteribacillus, and Lactococcus. Their content varied at different stages of fermentation. All the microbiome presented a variety of changes in the microbial diversity of shrimp paste.\n\nImportanceMost research on the microbial diversity of shrimp paste has focused on the shrimp culture environment, or the chemical composition and sensory attributes of the paste. Little research has been conducted on the microbial diversity and composition of shrimp paste. The relationship between microbes and the flavor and quality of shrimp paste has thus been unknown. We therefore analyzed the microbial composition and variation of shrimp paste at different stages of fermentation. The dominant bacteria in fermentation prophase, metaphase, and anaphase were identified. Our preliminary findings give some insight into which microbes contribute to the flavor of shrimp paste and suggest how to improve its flavor. In addition, our findings are relevant to optimizing the production of shrimp paste and guaranteeing its quality and safety.

microbiology↗