The extracellular electron transfer (EET) that connects the intracellular metabolism of electroactive microorganisms to external electron donors/acceptors, is the foundation to develop diverse microbial electrochemical technologies. For a particular microbial electrochemical device, the surface chemical property of an employed electrode material plays a crucial role in the EET process owing to the direct and intimate biotic-abiotic interaction. The functional modification of an electrode surface with redox mediators has been proposed as an effectual approach to promote EET, but the underlying mechanism remains unclear. In this work, we investigated the enhancement of electrochemically polymerized riboflavin interface on the bidirectional EET of Shewanella putrefaciens CN32 for boosting bioelectrocatalytic ability. An optimal polyriboflavin functionalized carbon cloth electrode achieved about 4.3-fold output power density (∼707 mW/m2) in microbial fuel cells and 3.7-fold cathodic current density (∼0.78 A/m2) for fumarate reduction in three-electrode cells compared to the control, showing great increases in both outward and inward EET rates. Likewise, the improvement was observed for polyriboflavin-functionalized graphene electrodes. Through comparison between wild-type strain and outer-membrane cytochrome (MtrC/UndA) mutant, the significant improvements were suggested to be attributed to the fast interfacial electron exchange between the polyriboflavin interface with flexible electrochemical activity and good biocompatibility and the outer-membrane cytochromes of the Shewanella strain. This work not only provides an effective approach to boost microbial electrocatalysis for energy conversion, but also offers a new demonstration of broadening the applications of riboflavin-functionalized interface since the widespread contribution of riboflavin in various microbial EET pathways together with the facile electropolymerization approach.

Traditional anthropometric indices are used in diagnosing metabolic syndrome (MetS). This study aimed to propose a novel index, a product of waist and neck circumferences (PWNC), and compared its value with traditional anthropometric parameters in identifying the presence of MetS in Chinese adults with type 2 diabetes mellitus (T2DM).

Biased G protein-coupled receptor (GPCR) ligands, which preferentially activate G protein or β-arrestin signaling pathways, are leading to the development of drugs with superior efficacy and reduced side effects in heart disease, pain management, and neuropsychiatric disorders. Although GPCRs are implicated in the pathophysiology of Alzheimer's disease (AD), biased GPCR signaling is a largely unexplored area of investigation in AD. Our previous work demonstrated that GPR3-mediated β-arrestin signaling modulates amyloid-β (Aβ) generation in vitro and that Gpr3 deficiency ameliorates Aβ pathology in vivo. However, Gpr3-deficient mice display several adverse phenotypes, including elevated anxiety-like behavior, reduced fertility, and memory impairment, which are potentially associated with impaired G protein signaling. Here, we generated a G protein-biased GPR3 mouse model to investigate the physiological and pathophysiological consequences of selective elimination of GPR3-mediated β-arrestin signaling in vivo. In contrast to Gpr3-deficient mice, G protein-biased GPR3 mice do not display elevated anxiety levels, reduced fertility, or cognitive impairment. We further determined that G protein-biased signaling reduces soluble Aβ levels and leads to a decrease in the area and compaction of amyloid plaques in the preclinical AppNL-G-F AD mouse model. The changes in amyloid pathology are accompanied by robust microglial and astrocytic hypertrophy, which suggest a protective glial response that may limit amyloid plaque development in G protein-biased GPR3 AD mice. Collectively, these studies indicate that GPR3-mediated G protein and β-arrestin signaling produce discrete and separable effects and provide proof of concept for the development of safer GPCR-targeting therapeutics with more directed pharmacological action for AD.

Noncoding RNAs (ncRNAs) can finely control the expression of target genes at the posttranscriptional level in prokaryotes. Regulatory small RNAs (sRNAs) designed to control target gene expression for applications in metabolic engineering and synthetic biology have been successfully developed and used. However, the effect on the heterologous expression of species- or strain-specific ncRNAs in other bacterial strains remains poorly understood. In this work, a Pseudomonas stutzeri species-specific regulatory ncRNA, NfiS, which has been shown to play an important role in the response to oxidative stress as well as osmotic stress in P. stutzeri A1501, was cloned and transferred to the Escherichia coli strain Trans10. Recombinant NfiS-expressing E. coli, namely, Trans10-nfiS, exhibited significant enhancement of tolerance to oxidative stress. To map the possible gene regulatory networks mediated by NfiS in E. coli under oxidative stress, a microarray assay was performed to delineate the transcriptomic differences between Trans10-nfiS and wild-type E. coli under H2O2 shock treatment conditions. In all, 1184 genes were found to be significantly altered, and these genes were divided into mainly five functional categories: stress response, regulation, metabolism related, transport or membrane protein and unknown function. Our results suggest that the P. stutzeri species-specific ncRNA NfiS acts as a regulator that integrates adaptation to H2O2 with other cellular stress responses and helps protect E. coli cells against oxidative damage.

Obesity is associated with an increased risk of many metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain poorly understood. Recent studies have demonstrated that MicroRNA-mediated gene silencing plays an important role in hepatic triglyceride (TG) metabolism. In the present study, we aimed to investigate the pathological function of miR-361-5p in the development of NAFLD.

Primary hypertrophic osteoarthropathy (PHO) is a rare, autosomal, recessive genetic disease characterized by digital clubbing, periostosis, and pachydermia. The underlying cause for the pathogenesis of this disease is a defect in prostaglandin E2 (PGE2) degradation, caused by mutations in HPGD or SLCO2A1. In this study, we describe the clinical characteristics, SLCO2A1 mutations, and bone metabolic markers of a PHO pedigree from a Chinese consanguineous twin family.

Emerging evidence suggests that G protein-coupled receptor (GPCR) kinases (GRKs) are associated with the pathophysiology of Alzheimer's disease (AD). However, GRKs have not been directly implicated in regulation of the amyloid-β (Aβ) pathogenic cascade in AD. Here, we determine that GRKs phosphorylate a non-canonical substrate, anterior pharynx-defective 1A (APH1A), an integral component of the γ-secretase complex. Significantly, we show that GRKs generate distinct phosphorylation barcodes in intracellular loop 2 (ICL2) and the C terminus of APH1A, which differentially regulate recruitment of the scaffolding protein β-arrestin 2 (βarr2) to APH1A and γ-secretase-mediated Aβ generation. Further molecular dynamics simulation studies reveal an interaction between the βarr2 finger loop domain and ICL2 and ICL3 of APH1A, similar to a GPCR-β-arrestin complex, which regulates γ-secretase activity. Collectively, these studies provide insight into the molecular and structural determinants of the APH1A-βarr2 interaction that critically regulate Aβ generation.