SWI/SNF染色质重塑复合物亚基Baf60a调控能量代谢稳态的研究进展

代谢综合征是一种全球性的慢性流行病,其发病机理由遗传与环境等因素共同决定。表观遗传修饰是在基因的核苷酸序列不发生改变的情况下,通过可遗传的变化调控基因表达。近年来研究发现,表观遗传修饰能够应答于环境因素、调控基因表达和信号转导进程。其中,染色质重塑复合物SWI/SNF(SWItch/Sucrose non fermentable,SWI/SNF)关键亚基Baf60a,在维持机体能量代谢稳态过程中发挥着重要作用。文中重点阐述了生理和病理状态下,Baf60a维持机体脂质代谢、胆固醇代谢、尿素循环及代谢节律性稳态的分子机制。深入探讨以Baf60a为基点的能量代谢调控网络,有望为代谢综合征的改善和治疗提供潜在药物治疗靶点和扎实的研究依据。

Rectified Ion Transport in Ultra-thin Membrane Governed by Outer Membrane Electric Double Layer

of main observation and conclusion The outstanding combination of selectivity and permeability observed in ultra-thin nanoporous mem-branes atracts broad interest from both fundamental research and practical application aspects.t is reported that the asymmetrical ion transport can berealized through the modfication of polyelectrolytes on the outer membranes surface.However,the related mechanisms are til nclear which hinderstheir applications.Herein,we systematclly investigate the origin of the ion current rectification in heterogeneously charged ultra-thin nanopores.Thecalcuated resuts based on the contiuity model suggest that,the ion transport across the ulra-thin membrane is dominated by the charge on the outermembrane surfoce rather than the pore wal.the overlap of electric double layer outside the pore entrance is essential fpr the ion asymmetric transport.And t acordingly results in the fact that the ion concentration enrichment and depletion effect ocurring outside the nanopore orifices governs the highand low ionic conductance states under the applied bias.These features can be regulated by the membrane surface state,which is truly attractive be.Ccause the surfaces of the outer membrane can be easily modified by experimental approaches.These findings provide the renew inspiration for the design of high-performance 2D nanofluidic devices.

A deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori

Helicobacter pylori(H.pylori)is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis,and its high prevalence and resistance make it difficult to tackle.A graph neural network-based deep learning model,employing different training sets of 13,638 molecules for pre-training and fine-tuning,was aided in predicting and exploring novel molecules against H.pylori.A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H.pylori strains with minimum inhibitory concentrations(MICs)of 0.25-0.5μg/mL.Pharmacokinetic studies demonstrated an ideal gastric retention of 8,with the stomach concentration significantly higher than its MIC at 24 h post dose.Oral administration of 8 and omeprazole(OPZ)showed a comparable gastric bacterial reduction(2.2-log reduction)to the triple-therapy,namely OPZ+amoxicillin(AMX)+clarithromycin(CLA)without obvious disturbance on the intestinal flora.A combination of OPZ,AMX,CLA,and 8 could further decrease the bacteria load(2.8-log reduction).More importantly,the mono-therapy of 8 exhibited comparable eradication to both triple-therapy(OPZ+AMX+CLA)and quadrupletherapy(OPZ+AMX+CLA+bismuth citrate)groups.SecA and BamD,playing a major role in outer membrane protein(OMP)transport and assembling,were identified and verified as the direct targets of 8 by employing the chemoproteomics technique.n summary,by targeting the relatively conserved OMPs transport and assembling system,8 has the potential to be developed as a novel anti-H.pylori candidate,especially for the eradication of drug-resistant strains.