Ion selectivity and gating behavior of the CorA-type channel Bpss1228.

Magnesium is an essential element to sustain all forms of life. Total intracellular magnesium content is determined by the balance of magnesium influx and efflux. CorA is a divalent selective channel in the metal ion transport superfamily and is the major Mg2+ uptake pathway in prokaryotes and eukaryotic mitochondria. Previous studies have demonstrated that CorA showed distinct magnesium bound closed conformation and Mg2+-free states. In addition, CorA is regulated by cytoplasmic magnesium ions and its gating mechanism has been investigated by electron paramagnetic resonance technique and molecular dynamic simulations. Here, we report a study of the putative CorA-type channel Bpss1228 from Burkholderia pseudomallei, which has been shown to be significantly associated with pseudomallei infection. We expressed and purified the Bpss1228 in full-length. Subsequently, electrophysiological experiments further investigated the electrical characteristics of Bpss1228 and revealed that it was a strictly cation-selective channel. We also proved that Bpss1228 not only possessed magnesium-mediated regulatory property a remarkable ability to be modulated by magnesium ions. Finally, we observed the three-step gating behavior of Bpss1228 on planar lipid bilayer, and further proposed a synergistic gating mechanism by which CorA family channels control intracellular magnesium homeostasis.

Nanopore Electrochemistry for Pathogen Detection.

Pathogen infections seriously threaten human health, and there is an urgent demand for rapid and efficient pathogen identification to provide instructions in clinical diagnosis and therapeutic intervention. Recently, nanopore technology, a rapidly maturing technology which delivers ultrasensitive sensing and high throughput in real-time and at low cost, has achieved success in pathogen detection. Furthermore, the remarkable development of nanopore sequencing, for example, the MinION sequencer from Oxford Nanopore Technologies (ONT) as a competitive sequencing technology, has facilitated the rapid analysis of disease-related microbiomes at the whole-genome level and on a large scale. Here, we highlighted recent advances in nanopore approaches for pathogen detection at the single-molecule level. We also overviewed the applications of nanopore sequencing in pathogenic bacteria identification and diagnosis. In the end, we discussed the challenges and future developments of nanopore technology as promising tools for the management of infections, which may be helpful to aid understanding as well as decision-making.

Aminoglycosides with Anti-MRSA Activity: A Concise Review.

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti- MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

Traditional Chinese medicine for gouty arthritis: A protocol for meta-analysis.

BACKGROUND: Gouty arthritis (GA) is a chronic disease caused by monosodium urate crystal deposition. Repeated attacks of arthritis may lead to the deposition of urate to form gout stone, resulting in joint deformity and joint damage. Although GA is not fatal, it causes low work productivity and low quality of life. Western drug, such as febuxostat, colchicine, allopurinol, often cannot get satisfying curative effect, and may even lead to serious side effects, such as exfoliative dermatitis or uremia. However, the therapeutic effect of Traditional Chinese medicine is very satisfactory. The treatment effect of simiao powder, a Chinese patent medicine, combined with acupuncture was widely used on treatment of GA. Although it has been widely used in clinical practice, its relative effectiveness and safety have not been confirmed. Therefore, this study will use meta-analysis to verify the efficacy and safety of simiao powder combined with acupuncture in the treatment of GA. METHODS: All randomized controlled trial of simiao powder combined with acupuncture for the treatment of RA from their inception 29 October, 2020 will be searched form the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library. Two authors will independently select studies, extract data based on pre-designed inclusion and exclusion criteria. Methodological quality assessment and risk of bias will be assessed using Cochrane bias risk tool. All data analysis will be conducted using Revman5.3, WinBUGS 1.4.3, and Stata14.2 software. RESULTS: We will compare the different outcome indicators of various studies to provide a synthesis of the efficacy and safety of Simiao powder combined with acupuncture for GA patients. The main outcome measures included efficacy, remission rate (no drug symptoms), recurrence rate, clinical absolute score and relative score. Secondary outcome measures included related adverse reactions and uric acid concentration. CONCLUSION: The findings of the study will provide helpful evidence for the efficacy and safety of simiao powder combined with acupuncture in the treatment of GA. REGISTRATION NUMBER: This study protocol have been funded through a protocol registry. The registry number is INPLASY2020110028.

Traditional Chinese medicine for irritable bowel syndrome: A protocol for meta-analysis.

BACKGROUND: Irritable bowel syndrom (IBS) is a common functional gastrointestinal disorder which is characterized as recurrent abdominal pain, abdominal discomfort, and abnormal bowel habits such as diarrhea, constipation, both or alternate appear. Although IBS is not fatal, it seriously affects the patients' daily life and work. Western drug, such as antidiarrheals, gastrointestinal antispasmodic, often cannot get satisfying curative effects. However, the therapeutic effect of Traditional Chinese medicine (TCM) on IBS is very satisfactory which was shown in a large number of randomized controlled trials. Although TCM has been widely used in clinical practice, its relative effectiveness and safety have not been confirmed. Therefore, this study will use meta-analysis to verify the efficacy and safety of different types of TCM in the treatment of IBS. METHODS: We search the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library for all randomized controlled trial of TCM for the treatment of IBS from their inception to Oct 15, 2020. Two authors will independently select studies, extract data based on predesigned inclusion and exclusion criteria. Methodological quality assessment and risk of bias will be assessed using Cochrane bias risk tool. All data analysis will be conducted using Revman5.3, WinBUGS 1.4.3, and Stata14.2 software. RESULTS: This study will compare the different outcome indicators of various studies directly and indirectly, and provide a high-quality synthesis of effectiveness and safety of different TCM methods for patients with IBS. The main outcome indicators include effectiveness, remission rate (no drug symptoms), relapse rate, clinical absolute score, and relative score. Secondary outcome indicators included related adverse reactions and serum serotonin concentration. CONCLUSION: The conclusion of this systematic review will provide a high-quality evidence based on the efficacy and safety of different TCM treatment methods for IBS. REGISTRATION NUMBER: This study protocol has been funded through a protocol registry. The registry number is INPLASY2020100052.

Association of TLR4 Gene rs2149356 polymorphism with primary gouty arthritis in a case-control study.

BACKGROUND: The toll-like receptor (TLR)4-interleukin1ß (IL1ß) signaling pathway is involved in the monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether the TLR4 gene rs2149356 SNP is associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1ß signaling pathway molecules expression. METHODS AND FINDINGS: The rs2149356 SNP was detected in 459 GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1ß were measured in different genotype carriers, and correlations between TLR4 gene SNP and TLR4 mRNA, IL1ß were investigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P<0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (OR = 1.88); this finding was not influenced by making adjustments for the components of possible confounders (adjusted OR = 1.96). TLR4 mRNA and IL1ß were significantly increased in the TT genotype from acute GA patients (P<0.05, respectively), and lipids were significantly different among three genotypes in the GA patients (P<0.05, respectively). CONCLUSIONS: The TLR4 gene rs2149356 SNP might be associated with GA susceptibility, and might participate in regulating immune, inflammation and lipid metabolism. Further studies are required to confirm these findings.

[Comparative analysis of clinical indicators of gout patients of different syndrome types and its significance].

OBJECTIVE: To understand the difference in clinical indicators of gout patients of different Chinese medical syndromes and its clinical significance. METHODS: Form November 2011 to December 2012, syndrome typed were 257 male gout in-/outpatients from Affiliated Hospital of Chuanbei Medical College. Another 50 healthy male subjects were recruited as the control. Their clinical and laboratory data were collected. All were excluded from infections and other inflammatory diseases. RESULTS: Four syndrome types existed in gout patients, i.e., intermingled phlegm-stasis blood syndrome (IPSBS), obstruction of dampness and heat syndrome (ODHS), Pi-deficiency induced dampness syndrome (PDIDS), qi-blood deficiency syndrome (QBDS). Of them, 53 acute phase gout patients suffered from IPSBS, 41 from ODHS, 25 from QBDS, and 17 from PDIDS; 41 non-acute phase gout patients suffered from QBDS, 40 from PDIDS, 24 from ODHS, and 16 from IPSBS. Statistical analysis of clinical data showed that, when compared with the normal control group, there was statistical difference in blood routines (WBC, GR, LY, MO) and blood biochemical indices (UA, Ur, Cr, ALT, AST, ALB, GLOB, TG, HDL-C, VLDL-C, apoA, apoB100) of gout patients of different syndromes (P < 0.05, P < 0.01). There was also statistical difference or correlation among different syndromes (P < 0.05). CONCLUSIONS: In the acute phase gout patients, IPSBS and ODHS were dominated, while in the non-acute phase gout patients, QBDS and PDIDS were often seen. In patients of IPSBS and ODHS, inflammation and immune response were more obvious, indicating that better efficacy might be achieved by clearing heat and removing blood stasis associated anti-inflammatory and immune regulation therapies. In patients of QBDS and PDIDS, impaired renal functions were more significant, indicating that better efficacy might be achieved by invigorating Pi and tonifying Shen dominated treatment.