Biology subjects

Wang, Y. Y.

Publications and source records attributed to Wang, Y. Y..

6 recordsLinked to original sources

bioRxiv2026

Robust T and B cell activation is associated with rapid clearance of infectious SARS-CoV-2

The immunologic correlates of rapid clearance of SARS-CoV-2 shedding are not well understood, partly due to challenges of collecting samples early after infection and the fact that most studies do not measure infectious virus. Here, we performed mass cytometry profiling of peripheral blood cells collected from people 4-6 days after onset of symptoms from acute SARS-CoV-2 infection who underwent daily nasopharyngeal testing for SARS-CoV-2 culture positivity. We identified broad and coordinated activation of innate and adaptive immune cells in unvaccinated individuals with primary infection. Faster clearance of infectious virus shedding was associated with robust adaptive immune cell activation and proliferation, namely among cytotoxic CD8+, CD4+, and {gamma}{delta} T cells and plasmablasts. In contrast, vaccinated individuals who rapidly cleared breakthrough infection showed minimal cellular immune activation. Our findings identify early immune correlates of rapid clearance of infectious SARS-CoV-2 shedding that may inform future prevention and therapeutic approaches to reduce disease burden and transmission.

immunology↗

bioRxiv2026

AFilter: Improved Antibody Epitope Prediction by Machine Learning-Optimized Interface Energy Filtering of AlphaFold3-Predicted Complex

AlphaFold3 (AF3) predicts protein-complex structures from sequence with near-experimental accuracy on many targets, substantially lowering the cost of mechanistic and therapeutic discovery. However, application to antibody epitope prediction is hampered by an approximately 63% failure rate. Comparing successful and failed AF3 predictions across antibody-antigen and nanobody-antigen complexes, we found that failed predictions share a distinctive energetic signature: distorted CDR-loop geometries and elevated van der Waals strain at the interface. Building upon these observations, we developed a machine learning-based interface energy filtering framework, designated AFilter, capable of eliminating over 90% of erroneous predictions while retaining >90% of true positives. Compared with ipTM-based filtering, AFilter improved accuracy from 82.7% to 97.7% for nanobody-antigen complexes and from 79.4% to 96.3% for antibody-antigen complexes, while simultaneously raising the true positive rate from 69.8% to 96.4% and from 63.1% to 92.5%, respectively. When applied to NeuroMab antibodies of unknown structure, AFilter prioritized high-confidence epitope predictions that AF3 sampling alone could not reliably surface. As a lightweight post-hoc filter (<5% computational overhead) that requires no re-docking, AFilter is directly compatible with existing AF3 prediction pipelines and, in principle, transferable to other diffusion-based complex predictors, providing a practical quality-assurance layer for antibody epitope mapping in early-stage drug discovery.

bioinformatics↗

bioRxiv2023

The tumour suppressor Fat1 is dispensable for normal murine haematopoiesis

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vavi-Cre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hemopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine haematopoiesis.

cancer biology↗

bioRxiv2023

Gender-specific impact of trans 10, cis 12-conjugated linoleic acid on pai transgenic female mice

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.

physiology↗

bioRxiv2023

Metabolic impact of trans 10, cis 12-conjugated linoleic acid in pai transgenic mice

Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) from ruminant-derived foodstuffs can induce body fat loss in mammals after oral administration, while its mechanism on fat reduction has yet to be clarified fully until now. In the current study, a transgenic mouse that produced t10c12-CLA had been generated by inserting the Propionibacterium acnes isomerase (Pai) expression cassette into the Rosa26 locus, and its male offspring were used to decipher an irreversible long-term impact of t10c12-CLA on health and its mechanism of action. Compared to their wild-type C57BL/6J littermates, comprehensive phenotype profiling of biallelic pai/pai mice indicated that white fat was decreased while brown fat was increased reversely; meanwhile, more heat was released and the central activities were reduced. Besides decreased plasma triglycerides in both pai genotypes and increased serum FGF21 in pai/wt mice, RNA and protein analysis revealed that the fatty acid oxidation and thermogenesis capacity of brown adipose tissues were elevated via CPT1B and UCP1/2 over-expression. The results indicate that the t10c12-CLA-induced fat loss might be caused by the excess FGF21 and the increased mass and extra thermogenesis of brown adipose tissue in transgenic mice.

physiology↗

bioRxiv2019

Inhibitory effect of Bacillus subtilis WL-2 and its IturinA lipopeptides against Phytophthora infestans

Potato late blight triggered by Phytophthora infestans ((Mont.) de Bary) represents a great food security threat worldwide and is difficult to control. Currently, Bacillus spp. have been considered biocontrol agents to control many fungal diseases. Here, Bacillus subtilis WL-2 was selected as the antifungal strain with the most potential against P. infestans mycelium growth. Additionally, the functional metabolites extracted from WL-2 were identified as IturinA-family cyclic lipopeptides (CLPs) via high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS). Analyses using scanning and transmission electron microscopy (SEM and TEM) revealed that IturinA caused a change in the mycelial surface and damage to the internal cell structure, including cell membrane disruption and irregular organelle formation. Moreover, propidium iodide staining and nucleic acid and protein release were detected to clarify the cell membrane damage caused by IturinA. Additionally, IturinA triggered reactive oxygen species (ROS) generation and malondialdehyde (MDA) production. Mitochondrial membrane potential (MMP), mitochondrial respiratory chain complexes activity (MRCCA), respiratory control rate (RCR), and oxidative phosphorylation efficiency (P/O) assays indicated that P. infestans mitochondria affected by IturinA were so seriously damaged that the MMP and MRCCA declined remarkably and that mitochondrial ATP production ability was weakened. Therefore, IturinA induces cell membrane damage, oxidative stress, and dysfunction of mitochondria, resulting in P. infestans hyphal cell death. As such, the results highlight that B. subtilis WL-2 and IturinA have great potential as candidates for inhibiting P. infestans mycelium growth and controlling potato late blight.\n\nIMPORTANCEPotato (Solanum tuberosum L.) is the fourth most common global food crop, and its planting area and yield increase yearly. Notably, in 2015, China initiated a potato staple food conversion strategy, and by 2020, approximately 50% of potatoes will be consumed as a staple food. The plant pathogen fungus Phytophthora infestans ((Mont.) de Bary) is the culprit of potato late blight; however, biological agents rather than chemicals are highly necessary to control this threatening disease. In this study, we discovered an antifungal substance, IturinA, a lipopeptide produced by Bacillus subtilis WL-2. Moreover, our research revealed the actual mechanism of IturinA against P. infestans mycelium growth and clarified the potential of B. subtilis WL-2 and IturinA as a biocontrol agent against P. infestans mycelium growth as well as for controlling the development of late blight in potato cultivation.

microbiology↗