Biology subjects

wang, J.

Publications and source records attributed to wang, J..

7 recordsLinked to original sources

bioRxiv2026

Cholesteryl Ester as a Prognostic Biomarker In IDH-wildtype Glioblastoma

Current treatment of IDH-wildtype glioblastoma (GBM) relies on the first-line chemotherapy-temozolomide. Although MGMT methylation is routinely conducted to predict chemosensitivity, its efficacy is often compromised. Thus, there is an urgent need to discover more accurate prognostic biomarkers. Cholesteryl ester (CE) has been recently recognized as a key feature of GBM, however, its role in GBM prognosis remains poorly understood. We first employed label-free stimulated Raman scattering (SRS) imaging to quantitatively analyze CE level in intact tumor tissues obtained from IDH-wildtype GBM patients. Our result revealed significantly prolonged 2-year overall survival (OS) in patients with CE level [≥] 40% compared to those with CE level < 40%. CE outperformed MGMT methylation for 2-year OS prognosis (AUC: 0.836 vs. 0.763). Importantly, CE also achieved superior prognostic performance over MGMT methylation on an independent cohort, with higher sensitivity (0.856 vs. 0.667), specificity (0.833 vs. 0.583), NPV (1.00 vs. 0.667), PPV (0.833 vs. 0.583). Given synergistic effects between CE and MGMT methylation, we developed a prognostic model combining these two biomarkers. Specially, machine learning (XGBoost) model exhibited optimal performance in the training cohort (AUC: 0.920), and maintained its superior performance on the independent cohort (sensitivity: 0.946, specificity: 0.873, NPV: 1.00; PPV: 0.917). Mechanistically, integrative analysis of TCGA database linked poor prognosis to the coordinated upregulation of genes involved in cholesterol efflux, hydrolysis, transport, and inhibition of de novo synthesis, unraveling a possible underlying mechanism between poor prognosis and cholesterol metabolism. This work identified CE as a prognostic biomarker for IDH-wildtype GBM.

neuroscience↗

bioRxiv2025

ICFinder: ion channel identification and ion permeation residue prediction using protein language models

Ion channel dysfunction underlies many diseases (e.g., arrhythmias, epilepsy, cystic fibrosis), and uncharacterized channels may also contribute to pathology. Identifying such channels and their residues directly contacting the permeation pathway (i.e., ion permeation residues) is key to elucidating transport mechanisms and developing targeted therapies. Leveraging the protein language model ESM-2 and curated datasets, we developed BLAPE and CLAPE frameworks for high-throughput ion channel identification and permeation residue prediction. Our models outperformed existing methods, with 33%-171% improvements in Matthews correlation coefficients (MCC) across different datasets. Analysis of amino acid composition revealed enrichment for weakly polar residues among ion permeation sites. Case studies on four diverse ion channels highlighted that CLAPE consistently outperforms existing predictors and remains applicable to proteins lacking experimental structures, while also complementing structure-based pipelines such as AlphaFold3. We further applied our models to UniRef50 to predict potential ion channels, and made these results publicly available through the ICFinder webserver (https://tianlab-tsinghua.cn/icfinder/), providing a ready-to-use resource for the research community. All source code is available at https://github.com/JueWangTHU/ICFinder.

bioinformatics↗

bioRxiv2025

Plant coumarins enhance viral pathogenicity by miRNA-mediated apoptosis in insect herbivores

Plant secondary metabolites (PSM) influence the susceptibility of insect herbivores to entomoviruses, but the apoptosis mechanism is not clear. Among plant hosts screened, the level of coumarin is correlated with NPV-mediated mortality, with high coumarin levels associated with high mortality and low coumarin levels with low mortality. Flow cytometry and morphological experiments showed that coumarins increased the apoptosis rate in NPV-infected larvae. miRNA transcriptomic analysis of coumarin-exposed larvae identified downregulation of miR-8 and miR-6497-3p, which negatively correlate with expression of pro-apoptotic kinases MAPK and ASK1. In addition, miR-9c-5p is upregulated, suppressing the apoptosis inhibitor 14-3-3 protein zeta. Our study suggests plant coumarins increase the susceptibility of larvae to NPV through miRNA-mediated regulation of apoptotic pathways. These findings suggest viral biocontrol efforts may be more successful on certain host plants, and provide molecular insight into how plant defense chemicals synergize with entomoviruses to control agricultural pests.

ecology↗

bioRxiv2023

Chemical screens in aging-relevant human motor neurons identify MAP4Ks as therapeutic targets for amyotrophic lateral sclerosis

Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant motor neurons, we identify a neuroprotective compound and show that MAP4Ks may serve as therapeutic targets for treating ALS. The lead compound broadly improves survival and function of motor neurons directly converted from human ALS patients. Mechanistically, it works as an inhibitor of MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, and normalizes subcellular distribution of RANGAP1 and TDP-43. Finally, in an ALS mouse model we show that inhibiting MAP4Ks preserves motor neurons and significantly extends animal lifespan.

neuroscience↗

bioRxiv2020

An effective, safe and cost-effective cell-based chimeric vaccine against SARS-CoV2

More than one hundred vaccines against SARS-CoV-2 have been developed and some of them have entered clinical trials, but the latest results revealed that these vaccines still face great challenges. Here, we developed a novel cell-based gp96-Ig-secreting chimeric vaccine which is composed of two viral antigens, the RBD of spike protein, and a truncated nucleocapsid protein that could induce epitope-specific cytotoxic T lymphocytes but low antibody response. Syrian hamsters immunized with the cell-based vaccine produced high level of SARS-CoV-2 specific NAbs and specific T cell immunity which could eliminate RBD-truncated N-expressing cells, without the induction of antibody against N protein and other observed toxicity. This study provides a proof of concept for clinical testing of this safe, effective and cost-effective vaccine against SARS-CoV2 infection.

immunology↗

bioRxiv2019

Fibroblast growth factor-2 prevents synaptic pathology in minimal hepatic encephalopathy via NRG1/ErbB4 signaling

BackgroundMinimal hepatic encephalopathy (MHE) is implicated in the impairment of memory function. Fibroblast growth factor-2 (FGF2) is involved in modulating synaptic and neuronal formation. MethodsThe aim of this study is to examined the impacts of FGF2 on MHE pathology. Our study addressed whether FGF2 could trigger neuregulin-1 (NRG1) release to ameliorate synaptic impairment in MHE rats and in primary cultured neurons. ResultsThe results showed the decreased FGF2 expression in MHE brains. After treatment with FGF2, secreted neuregulin-1 (NRG1) and ErbB4 were increased, and the interaction of the 2 proteins was enhanced. Additionally, treatment with FGF2 or NRG1 induced synaptic formation, with increase in the activity of synapse and the density of dendritic spine, through Sirt1. NRG1 signaling was prevented by administration of FGF2, which acts through the FGFR1 in MHE rats. Finally, intracerebroventricular injection with FGF2 or NRG1 mitigated the impairment of synaptogenesis. ConclusionThe data suggest that FGF2 may be a promising latent therapeutic reagent for MHE pathogenesis.

neuroscience↗

bioRxiv2019

Phanerochaete chrysosporium strain B-22, a parasitic fungus infecting Meloidogyne incognita

We characterized the parasitism by strain B-22 of Phanerochaete chrysosporium on the eggs, second stage juveniles (J2), and adult females of the root-knot nematode (Meloidogyne Incognita). Strain B-22 had a strong lethal effect against M. incognita J2. The highest corrected mortality was 71.9% at 3 x 108 conidia mL-1. The estimated LC50 value was 0.96 x 108 conidia mL-1. Strain B-22 parasitized M. incognita eggs 2 days after treatment, causing the depression and dissolution of egg shells. The fungal spores parasitized J2 by gathering in the body wall, germinating to develop hyphae, and crossing the juvenile cuticle to dissolve it, thereby causing the shrinkage and deformation of the juvenile body wall. The spores and hyphae also attacked adult females, causing the shrinkage and dissolution of their bodies and leakage of contents in 5 days. Results of greenhouse experiments showed that different concentrations of P. chrysosporium effectively controlled different life stages of M. incognita and root knot symptoms in tomato plants. Moreover, the control efficacy increased with increasing conidial concentration; the best results were achieved with 3 x 108 cfu mL-1. In the roots, the highest inhibition rate was 84.61% for adult females, 78.91% for juveniles, 84.25% for the egg mass, and 79.48% for the gall index. The highest juvenile inhibition rate was 89.18% in the soil. Meanwhile, strain B-22 improved the plant growth. Thus, P. chrysosporium strain B-22 is safe for tomato plants while effectively parasitizing M. incognita, making it a promising biocontrol agent against M. incognita.

pathology↗