Biology subjects

wang, c.

Publications and source records attributed to wang, c..

8 recordsLinked to original sources

bioRxiv2026

Sequential assembly in vivo of the bacteriophage P22 genome translocation channel

Bacteriophage P22 ejects four internal proteins into infected cells to assemble a channel for genome translocation across the cell envelope. However, how these proteins cooperate to build the trans-envelope channel remains enigmatic. Using in situ single-particle cryogenic electron microscopy, we determined near-atomic in vivo structures of P22 infection intermediates, revealing how the tail hub protein gp10 templates the sequential assembly of three internal proteins gp7*, gp20 and gp16 into a ~50-nm trans-envelope channel that extends from the virion into the host cytoplasm. Functional analyses explain why phage DNA can be detected in supernatant fluids during infection by channel-defective mutants. Our structures also provide a mechanistic basis for the long-standing observation that a P22 virion lacking gp16 can be complemented, extra-cytoplasmically, by a co-infecting virion lacking gp20, thereby allowing the genome in the gp16-deficient particle to enter the host cytoplasm.

microbiology↗

bioRxiv2025

A new nitrogen biochemical process: Oxidization of ammonium into nitrogen gas using nitrate

The nitrifying bacteria oxidize ammonium into nitrite or nitrate under aerobic conditions, while the anaerobic ammonia-oxidizing bacteria utilize nitrite to oxidize ammonium into nitrogen gas under anaerobic conditions. There is no biochemical process that can directly oxidize ammonium into nitrogen gas using nitrate under anaerobic conditions. In this study, mature anaerobic ammonium oxidation (anammox) granular sludge was inoculated in an anaerobic nitrogen-removal system, while nitrate and ammonium were used as the influent substrates. The experiment was conducted for 537 days at a temperature of 30-32{degrees}C and a pH of 8.0-9.0. The transformation from nitrite-anammox to nitrate-anammox was stably achieved on the 350th day. The experimental results showed that, nitrate directly oxidized ammonium into nitrogen gas under anaerobic conditions. The produced gas consisted of 96.3% nitrogen and 3.7% carbon dioxide. The removal ratio of ammonium to nitrate was approximately 1.67:1, and the total inorganic nitrogen removal rate reached up to 290.20 mg/(L{middle dot}d). Unlike the nitrite-anammox reaction, this reaction was accompanied by an acid production process, which caused a decrease in pH. When the substrate was changed to nitrite and ammonium, the total nitrogen removal rate of only 1.1-1.3 mg/(L{middle dot}d) was achieved. This new biochemical reaction of nitrogen was defined as nitrate-anammox. The study reveals a new pathway of nitrogen transformation, providing novel insights into the global nitrogen cycle.

microbiology↗

bioRxiv2025

Joint Modeling of Longitudinal Biomarker and Survival Outcomes with the Presence of Competing Risk in Nested Case-Control Studies with Application to the TEDDY Microbiome Dataset

MotivationLarge-scale prospective cohort studies collect longitudinal biospecimens alongside time-to-event outcomes to investigate biomarker dynamics in relation to disease risk. The nested case-control (NCC) design provides a cost-effective alternative to full cohort biomarker studies while preserving statistical efficiency. Despite advances in joint modeling for longitudinal and time-to-event outcomes, few approaches address the unique challenges posed by NCC sampling, non-normally distributed biomarkers, and competing survival outcomes. ResultsMotivated by the TEDDY study, we propose "JM-NCC", a joint modeling framework designed for NCC studies with competing events. It integrates a generalized linear mixed-effects model for potentially non-normally distributed biomarkers with a cause-specific hazard model for competing risks. Two estimation methods are developed. fJM-NCC leverages NCC sub-cohort longitudinal biomarker data and full cohort survival and clinical metadata, while wJM-NCC uses only NCC sub-cohort data. Both simulation studies and an application to TEDDY microbiome dataset demonstrate the robustness and efficiency of the proposed methods.

bioinformatics↗

bioRxiv2024

Recombinant expression, purification, and antifungal activity of the novel antimicrobial peptide TaW662

Blumeria graminis f. sp. tritici (Bgt) is a significant wheat fungal pathogen, posing threats to both yield and quality. Antimicrobial peptides, with their broad-spectrum activities, hold promise in combating Bgt-induced wheat fungal diseases.In this study, we identified TaW662, an antifungal peptide gene sourced from the wheat-Thinopyrum intermedium disomic alien addition line SN6306. Through third-generation transcriptome sequencing, we obtained the full-length transcript of TaW662. Notably, TaW662 exhibited upregulated expression in response to powdery mildew infection in SN6306. Subcellular localization analysis revealed TaW662s extracellular secretion, suggesting its role in defense mechanisms. Additionally, the TaW662 protein was expressed in Escherichia coli, and the purified protein could inhibit the growth of Bgt in vitro. Utilizing the online alphafold2 server, we predicted the three-dimensional structure of TaW662, aiding in understanding its fungicidal mechanisms. Analysis of TaW662s physicochemical properties further supported its potential efficacy as a fungicide against Bgt. In conclusion, TaW662 emerges as a promising candidate for combating Bgt-induced wheat fungal diseases, warranting further exploration for agricultural disease management strategies. HighlightsTaW662, a secreted protein homologous to TaWIR1, is induced in wheat by Blumeria graminis f. sp. tritici (Bgt). The expression pattern of TaW662 in wheat under induced by Bgt was analysed using RNA-Seq technology. The three-dimensional structure of TaW662 was predicted using AlphaFold2. The growth of Bgt is inhibited by recombinant TaW662.

plant biology↗

bioRxiv2022

ARZIMM: A Novel Analytic Platform for the Inference of Microbial Interactions and Community Stability from Longitudinal Microbiome Study

Dynamic changes of microbiome communities may play important roles in human health and diseases. The recent rise in longitudinal microbiome studies calls for statistical methods that can model the temporal dynamic patterns and simultaneously quantify the microbial interactions and community stability. Here, we propose a novel autoregressive zero-inflated mixed-effects model (ARZIMM) to capture the sparse microbial interactions and estimate the community stability. ARZIMM employs a zero-inflated Poisson autoregressive model to model the excessive zero abundances and the non-zero abundances separately, a random effect to investigate the underlining dynamic pattern shared within the group, and a Lasso-type penalty to capture and estimate the sparse microbial interactions. Based on the estimated microbial interaction matrix, we further derive the estimate of community stability, and identify the core dynamic patterns through network inference. Through extensive simulation studies and real data analyses we evaluated ARZIMM in comparison with the other methods.

bioinformatics↗

bioRxiv2021

ICA treatment diabets induced bone loss via primary cilia/Gli2/Osteocalcin signaling pathway

Diabetes mellitus, as a metabolic system disorder disease, aggravates the disease burden of patients and affects the quality of human life. Diabetes-associated bone complications lead to decreased bone mechanical strength and osteoporosis. Evidences show that chronic hyperglycemia and metabolic intermediates, such as inflammatory factor, reactive oxygen species (ROS) and advanced glycation end products (AGEs), are regarded as dominant hazardous factors of primary cilia/Gli2 signal disorders. Case studies have demonstrated abnormal bone metabolism in diabetics, however, how diabetes damages primary cilia/Gli2 signal is largely unknown. Therefore, we studied the effects of diabetes on femoral primary cilia by establishing a Streptozocin (STZ)-induced diabetic (Sprague Dawley) SD rat model and diabetic bone loss cell model in vitro. Our results confirmed that diabetes impaired femur primary cilia, osteoblast differentiation and mineralization by inhibiting primary cilia/Gli2 signaling pathway, additionally, Icariin(ICA) treatment could rescue the impairment of osteoblast differentiation caused by high glucose medium in vitro. ICA activated primary cilia/Gli2/osteocalcin signaling pathway of osteoblasts by protecting primary cilia from glucotoxicity imposed by diabetes, intact primary cilia could be as anchoring sites, in which Gli2 was processed and modified, and matured Gli2 entered the nucleus to initiate downstream osteocalcin gene transcription. Additionally, ICA inhibited ROS production of mitochondria, thus balanced mitochondrial energy metabolism and oxidative phosphorylation. All results suggest that ICA can protect the primary cilia and mitochondria of osteoblast by reducing intracellular ROS, thereby recover primary cilia/Gli2 signaling pathway to facilitate osteoblast differentiation and mineralization, suggesting that ICA has potential as a novel type of drug treating bone loss induced by diabetes.

cell biology↗

bioRxiv2019

The characterization of a humanized rabbit anti-TNF α monoclonal antibody?A nationwide RA treatment drug study

Tumor necrosis factor alpha (TNF) is now regarding as a key role in the pathogenesis of immune-mediated disease such as Rheumatoid arthritis (RA), Crohn's Disease, Psoriatic arthritis and Plaque Psoriasis. HERE we have successfully developed an anti-hTNF monoclonal rabbit antibody(HZ3M) with high binding and neutralizing activity based on RabMAbs platform. Rabbit hybridomas, immunized subcutanrously with 0.4 mg human TNF, were generated from the rabbit splenocytes and a total of 142 hybridoma clones with specific binding to human TNFa were obtained. The anti-TNFa RabMAbs showed better neutralizing activity and higher antigen binding affinity compared to Humira and Remicade, the elimination phase half-life 58.2h respectively. In vivo efficay studies, normal mice or human TNF-alpha transgenic mice were injected with 1.0 mg/kg Humira (positive control), HZ3M at 0.33?1.0 or 3.0 mg/kg, or solvent (negative control), showed that HZ3M is able to bind and neutralize hTNF in transgenic and normal mice as well as normal rabbits.Clearly dose-dependent response can be determined. Compared to marketed anti-TNFa drug Humira, the efficacy of HZ3M is seems to show significant longer holding time.Our observations indicate that the HZ3M derived from RabMAb preclinical safety study, and might have a therapeutic role in RA treatment.

cell biology↗

bioRxiv2019

Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely unexplored. Here, we identify an uncharacterized human lncRNA from influenza A virus (IAV) patients, antivirus and activate neutrophil (AVAN), that is significantly up-regulated upon virus infection. Mechanistically, nuclear lncRNA-AVAN positively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Furthermore, we also found that cytoplasmic lncRNA-AVAN directly binds tripartite motif containing 25 (TRIM25) and enhances the association of TRIM25 and Retinoic acid inducible gene-1 proteins (RIG-I) and the ubiquitylation of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune signaling. More importantly, we enforced the expression of AVAN in transgenic mice and found that it significantly alleviated IAV virulence and virus production. Collectively, these findings highlight the potential clinical implications of lncRNA-AVAN as a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.

immunology↗