Yi Zhang’s research while affiliated with Shenzhen Second People's Hospital and other places

The application of resonant magnetic perturbation (RMP) with toroidal mode number n = 1 on HL-3 tokamak inhibits the L-H transition at specific heating power. Following RMP application, the electron density increases in the outer plasma region (ρ > 0.85, where ρ is the normalized toroidal flux), while the electron/ion temperature decreases. Notably, the equilibrium flow shear in the edge region is substantially reduced. This reduction, combined with enhanced micro-instabilities driven by increased profile gradients, leads to enhanced turbulence levels. Consequently, the diminished flow shear becomes less effective in suppressing turbulence, providing a comprehensive explanation for the inhibited access to H-mode. Through a modified one-dimensional predator–prey model that incorporates the effects of RMP-induced radial magnetic perturbations, we have conducted a quantitative analysis of the turbulence and flow dynamics during the L-H transition process. Our results indicate that as the strength of magnetic perturbation increases, the turbulence intensity increases and edge flow shear decreases, in agreement with experimental observations. Additionally, we found that the L-H transition power threshold increases almost linearly with the square of the radial magnetic perturbation intensity. These results enhance our understanding of RMP-induced changes in edge plasma transport, providing valuable insights for optimizing the operation of future tokamaks and improving the performance of fusion reactors.

Heart failure is associated with myocardial fibrosis, a pivotal histopathological feature arising from β-adrenergic receptor (β-AR) stimulation through sympathetic nervous system activation. Augmented glutaminolysis with increased bioavailability of α-ketoglutarate (α-KG) is suggested to contribute to fibrogenesis and changes in cellular gene expression. KCa3.1 is a calcium-activated potassium channel expressed in fibroblasts and has been implicated in mediating fibrosis, yet the putative interactions between glutaminolysis and KCa3.1 in β-AR-mediated cardiac fibrosis remain poorly understood. Here, we performed a series of in vitro and in vivo experiments to investigate how α-KG might influence the expression of KCa3.1 in the context of experimental myocardial fibrosis driven by β-AR activation. In cultured adult mouse cardiac fibroblasts, α-KG exposure resulted in the upregulation of KCa3.1 mRNA and protein levels that were commensurate with the dose and duration of exposure, and also led to increased KCa3.1 channel currents. Exposure to α-KG led to a significant decrease in levels of histone methylation (H3K27me3) within the KCa3.1 promoter, a decrease in the association of the transcription repressor REST from this site, as well as an enrichment of transcription activator AP-1 binding. The exacerbated fibrotic signaling induced by α-KG in cultured fibroblasts was suppressed by functional inhibition of KCa3.1 or by genetic knockdown of Kcnn4. Moreover, β-AR activation by isoproterenol significantly augmented glutaminolysis mediated by glutaminase 1 (GLS1) and significantly increased α-KG levels detected in the supernatant of cultured fibroblasts and cardiomyocytes. In addition, isoproterenol-induced KCa3.1 expression in fibroblasts was curtailed by treatment with the GLS1 inhibitor CB-839, or by GLS1 gene knockdown, or by treatment with the selective β2-AR antagonist, ICI118551. In mouse models of established cardiac fibrosis evoked by isoproterenol-stimulation or β2-AR overexpression, treatment with CB-839 for 4 weeks suppressed the phenotypic features of fibrosis, and this was associated with a decline in α-KG tissue content, a lack of histone demethylation at the KCa3.1 promoter, as well as suppression of KCa3.1 expression. Taken together, our study demonstrates for the first time that glutaminolysis contributes to β-AR activation-induced myocardial fibrosis via α-KG-stimulated KCa3.1 expression. We anticipate that treatments which target the β-AR/GLS1/α-KG/KCa3.1 signaling pathway might be effective for cardiac fibrosis.

Swallowing disorder or dysphagia is one of the common functional disorders in stroke survivors, and its early screening is important for reducing patient dependence, pneumonia incidence, mortality, and shortening the hospital stay. However, the commonly used methods to examine dysphagia, which include Toronto bedside swallowing screening test, volume viscosity swallowing test, and swallowing angiography screening/examination, are all invasive with the risk of aspiration. Here we have undertaken a detailed voice analysis on stroke patients with dysphagia by monitoring a series of acoustic parameters including maximum volume, maximum pitch, glottal noise excitation ratio, fundamental frequency perturbation, amplitude perturbation (Shimmer), maximum pronunciation time, irregularity, breath sound, overall severity, and voice disorder severity index. We show that all these acoustic parameters change significantly for the stroke patients with dysphagia compared with the healthy group as well as stroke group with no dysphagia, and the changes are correlated with the severity of pharyngeal residue especially for Shimmer and overall severity of the voice. Our findings suggest that voice analysis, which is quick and non-invasive, may give an important initial indication on the severity of dysphagia and cross-validate results from swallowing tests that clinicians may further pursue for a thorough diagnosis of dysphagia.

Introduction. Accumulating evidence indicates a significant association between gut microbiota and the risk of developing pyogenic arthritis (PA). However, their causal relationship has yet to be elucidated. Hypothesis. The gut microbiota is causally associated with the risk of PA. Aim. The Mendelian randomization (MR) methodology was employed to assess the potential causal effects of gut microbiota on the susceptibility to PA. Methodology. A two-sample MR study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis ( n =13,266) conducted by the MiBioGen consortium. The summary statistics of PA were obtained from the R11 release data provided by the FinnGen consortium (2,441 cases and 2,87,796 controls). Inverse-variance weighted (IVW) model, weighted median estimator model, weighted model-based method and MR-Egger regression (MER) model were used to examine the causal association between gut microbiota and PA. To assess the heterogeneity and pleiotropic effects of the identified instrumental variables (IVs), we utilized several analytical methods, including the leave-one-out sensitivity analysis, the MR Pleiotropy Residual Sum and Outlier test and Cochran’s Q test. Results. Utilizing the IVW method, we identified six bacterial traits that were negatively correlated with PA: Eubacterium eligens group [OR: 0.6057; 95 % confidence interval (CI): 0.4525 to 0.8107; P =0.0007], Barnesiella (OR: 0.7456; 95 % CI: 0.5760 to 0.9651; P =0.0258), Coprococcus2 (OR: 0.7257; 95 % CI: 0.5352 to 0.9840; P =0.0391), Ruminococcaceae UCG005 (OR: 0.7562; 95 % CI: 0.5920 to 0.9660; P =0.0252), E. oxidoreducens group (OR: 0.7311; 95 % CI: 0.5547 to 0.9637; P =0.0262) and Lachnospiraceae FCS020 group (OR: 0.7825; 95 % CI: 0.6135 to 0.9981; P =0.0482), respectively. On the contrary, four bacterial traits were positively correlated with PA: Adlercreutzia (OR 1.3210, 95 % CI 1.0181–1.7141, P =0.0362), Holdemania (OR 1.2239, 95 % CI 1.0013–1.4960, P =0.0485), Anaerostipes (OR 1.3614, 95 % CI 1.0189–1.8191, P =0.0369) and Butyricimonas (OR 1.2627, 95 % CI 1.0016–1.5921, P =0.0484), respectively. No significant heterogeneity among IVs or evidence of horizontal pleiotropy was detected. Conclusion. Our research demonstrates a potential causal link between various gut microbiota and the risk of PA. Further research is imperative to elucidate the mechanisms by which gut microbiota influence the pathogenesis of PA.