Biology subjects

JIANG, Y.

Publications and source records attributed to JIANG, Y..

3 recordsLinked to original sources

bioRxiv2025

β-cell-specific Non-invasive Ultrasound Stimulation to Enhance Insulin Release and Glucose Control in Mice

AbstractsDiabetes poses a significant global health burden, with complications such as cardiovascular disease, stroke, and kidney failure. While insulin therapy is central to type 2 diabetes (T2D) management, its limitations--including rapid degradation and the need for frequent injections--highlight the demand for non-invasive alternatives. Here, we present an ultrasound (US)-mediated approach to enhance insulin release by selectively stimulating pancreatic {beta}-cells via targeted microbubbles (MBs). In vitro experiments using RINm5F {beta}-cells demonstrated that US-MB stimulation induces significant calcium influx and subsequent insulin release. In addition, this method effectively decreased blood glucose levels in mice by promoting insulin release. Mechanistic studies revealed that mechanosensitive ion channels play a pivotal role, as their inhibition (via GdCl3) abolished the ultrasonic effect. Importantly, the approach exhibited high biosafety, with no detectable cell death or tissue damage. Our findings establish ultrasound-stimulated {beta}-cell targeting as a promising non-invasive strategy for diabetes treatment, offering a potential alternative to conventional insulin therapy.

bioengineering↗

bioRxiv2025

Molecular Mechanism of pH Sensing and Activation in GPR4 Reveals Proton-Mediated GPCR Signaling

Maintaining pH homeostasis is critical for cellular function across all living organisms. Proton-sensing G protein-coupled receptors (GPCRs), particularly GPR4, play a pivotal role in cellular responses to pH changes, yet the molecular mechanisms underlying their proton sensing and activation remain incompletely understood. Here we present high-resolution cryo-electron microscopy structures of GPR4 in complex with G proteins under physiological and acidic pH conditions. Our structures expose an intricate proton-sensing mechanism driven by a sophisticated histidine network in the receptors extracellular domain. Upon protonation of key histidines under acidic conditions, a remarkable conformational cascade is initiated, propagating from the extracellular region to the intracellular G protein-coupling interface. This dynamic process involves precise transmembrane helix rearrangements and conformational shifts of conserved motifs, mediated by strategically positioned water molecules. Notably, we discovered a bound bioactive lipid, lysophosphatidylcholine, which has positive allosteric effects on GPR4 activation. These findings provide a comprehensive framework for understanding proton sensing in GPCRs and the interplay between pH sensing and lipid regulation, offering insights into cellular pH homeostasis and potential therapies for pH-related disorders.

molecular biology↗

bioRxiv2024

Discovery and Engineering of a New BvCas12a Nuclease for Mammalian Genome Editing and Nucleic Acid Detection

Cas12a is an RNA-guided endonuclease that has emerged as a powerful gene-editing tool. We have identified a novel Cas protein, BvCas12a, from Butyricimonas virosa with a 5-TYTN protospacer adjacent motif (PAM). BvCas12a exhibits double-stranded DNA cleavage activity in vitro and genome editing activity in eukaryotic cells. Though the editing efficiency of BvCas12a is marginally lower than that of AsCas12a, the editing specificity of BvCas12a in eukaryotic cells is comparable or superior to that of AsCas12a. Moreover, BvCas12a exhibits substantial collateral activity and can detect HPV DNA effectively and accurately in conjunction with isothermal amplification, highlighting its potential in nucleic acid diagnostics. Furthermore, we have engineered BvCas12a to create two variants, BvCas12a-R (N549R, T606P) and BvCas12a-RVR (N549R, K555V, C559R, T606P). These variants recognize expanded 5-YYN and 5-YN PAM in vitro, respectively. Additionally, they exhibit higher editing activity than wild-type BvCas12a and recognize 5-YYN PAM in vivo at all sites detected. In conclusion, we have identified a novel BvCas12a protein with high specificity and engineered two variants with broader PAM compatibility and improved genome editing efficiency. These findings offer a potent gene editing tool for application in scientific research, gene therapy, and nucleic acid diagnostics.

genomics↗