Relationship between weight-adjusted-waist index and erectile dysfunction in the United State: results from NHANES 2001-2004

ObjectiveThe purpose of this study is to examine the association between a novel adiposity parameter, the weight-adjusted-waist index (WWI), and erectile dysfunction (ED).MethodsAccording to National Health and Nutrition Examination Survey (NHANES) 2001-2004, a total of 3884 participants were categorized as ED and non-ED individuals. WWI was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). Weighted univariable and multivariable logistic regression models were conducted to assess the correlation between WWI and ED. Smooth curve fitting was utilized to examine the linear association. The receiver operating characteristic (ROC) curve and DeLong et al.’s test were applied to compare the area under curve (AUC) value and predictive power among WWI, body mass index (BMI), and WC for ED.ResultsWWI was positively related to ED with the full adjustment [odds ratio (OR)=1.75, 95% confidence interval (95% CI): 1.32-2.32, p=0.002]. After converting WWI to a categorical variable by quartiles (Q1-Q4), compared to Q1 the highest WWI quartile was linked to an obviously increased likelihood of ED (OR=2.78, 95% CI: 1.39-5.59. p=0.010). Subgroup analysis revealed the stability of the independent positive relationship between WWI and ED. It was shown that WWI had a stronger prediction for ED (AUC=0.745) than BMI (AUC=0.528) and WC (AUC=0.609). Sensitivity analysis was performed to verify the significantly positive connection between WWI and stricter ED (OR=2.00, 95% CI: 1.36-2.94, p=0.003).ConclusionAn elevated WWI was related to higher risks of ED in the United State adults, and a stronger predictive power of WWI for ED was observed than BMI and WC

A Role for Cdc2- and PP2A-Mediated Regulation of Emi2 in the Maintenance of CSF Arrest

Vertebrate oocytes are arrested in metaphase II of meiosis prior to fertilization by cytostatic factor (CSF). CSF enforces a cell cycle arrest by inhibiting the anaphase promoting complex (APC), an E3 ubiquitin ligase that targets Cyclin B for degradation. Although Cyclin B synthesis is ongoing during CSF arrest, constant Cyclin B levels are maintained. To achieve this, oocytes allow continuous slow Cyclin B degradation, without eliminating the bulk of Cyclin B, which would induce release from CSF arrest. However, the mechanism that controls this continuous degradation is not understood

Synthesis and biological evaluation of new 13-n-nonylprotoberberine derivatives as antitubercular agents

Tuberculosis is a serious threat to public health throughout the world. A series of new 13-n-nonylprotoberberine derivatives was designed, synthesized and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis strain H37Rv. Several compounds (2, 11a-c, 11g, 13d, 15c) exhibited excellent anti-tubercular activity with an MIC below 1.0μg/mL. Notably, compound 13d showed potential antibacterial effect against both drug-susceptible and multidrug-resistant (MDR) M. tuberculosis with MIC ranges of 0.0625–1.0 μg/mL. These results suggest a mode of action different from that of the current anti-mycobacterial drugs rifampicin and isoniazid. Hence, compound 13d is an attractive lead compound for the development of new antitubercular agents

Accelerating AutoDock Vina with GPUs

AutoDock Vina is one of the most popular molecular docking tools. In the latest benchmark CASF-2016 for comparative assessment of scoring functions, AutoDock Vina won the best docking power among all the docking tools. Modern drug discovery is facing a common scenario of large virtual screening of drug hits from huge compound databases. Due to the seriality characteristic of the AutoDock Vina algorithm, there is no successful report on its parallel acceleration with GPUs. Current acceleration of AutoDock Vina typically relies on the stack of computing power as well as the allocation of resource and tasks, such as the VirtualFlow platform. The vast resource expenditure and the high access threshold of users will greatly limit the popularity of AutoDock Vina and the flexibility of its usage in modern drug discovery. In this work, we proposed a new method, Vina-GPU, for accelerating AutoDock Vina with GPUs, which is greatly needed for reducing the investment for large virtual screens and also for wider application in large-scale virtual screening on personal computers, station servers or cloud computing, etc. Our proposed method is based on a modified Monte Carlo using simulating annealing AI algorithm. It greatly raises the number of initial random conformations and reduces the search depth of each thread. Moreover, a classic optimizer named BFGS is adopted to optimize the ligand conformations during the docking progress, before a heterogeneous OpenCL implementation was developed to realize its parallel acceleration leveraging thousands of GPU cores. Large benchmark tests show that Vina-GPU reaches an average of 21-fold and a maximum of 50-fold docking acceleration against the original AutoDock Vina while ensuring their comparable docking accuracy, indicating its potential for pushing the popularization of AutoDock Vina in large virtual screens

2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione isolated from Averrhoa carambola L. root inhibits high glucose-induced EMT in HK-2 cells through targeting the regulation of miR-21–5p/Smad7 signaling pathway

Objective: 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione (DMDD) isolated from Averrhoa carambola L. root, has been proven therapeutic effects on diabetic kidney disease (DKD). This research aims to assess DMDD’s effects on DKD and to investigate its underlying mechanisms, to establish DMDD as a novel pharmaceutical agent for DKD treatment. Methods: The human renal tubular epithelial (HK-2) cells were induced by high glucose (HG) to mimic DKD and followed by DMDD treatment. The cytotoxicity of DMDD was assessed using the Cell Counting Kit-8 (CCK-8) assay. The migratory capacity of HK-2 cells was evaluated through transwell and scratch-wound assays. To investigate the effect of Smad7 and miR-21–5p, lentiviral transfection was employed in HK-2 cells. Additionally, the expression of proteins related to epithelial-mesenchymal transition (EMT) and TGFβ1/Smad2/3 pathway was checked by QRT-PCR, Western blot, and immunofluorescence techniques. Results: This study has shown that DMDD significantly suppresses cell migration and the expression of Vimentin, α-SMA, TGFβ1, and p-Smad2/3 in HK-2 cells under HG conditions. Concurrently, DMDD enhances the protein expression of E-cadherin and Smad7. Intriguingly, the therapeutic effect of DMDD was abrogated upon Smad7 silencing. Further investigations revealed that DMDD effectively inhibits miR-21–5p expression, which is upregulated by HG. Downregulation of miR-21–5p inhibits the activation of the TGFβ1/Smad2/3 pathway and EMT induced by HG. In contrast, overexpression of miR-21–5p negates DMDD’s therapeutic benefits. Conclusion: DMDD mitigates EMT in HG-induced HK-2 cells by modulating the miR-21–5p/Smad7 pathway, thereby inhibiting renal fibrosis in DKD. These findings suggest that DMDD holds promise as a potential therapeutic agent for DKD

The complete mitochondrial genome of Tetragonia tetragonioides (Pall.) Kuntze and its phylogenetic implications

The complete mitochondrial genome sequence of Tetragonia tetragonioides (Pall.) Kuntze was assembled and characterized in the present study. The mitochondrial genome was 347,227 bp in length and had a GC content of 43.84%, including 24 transfer RNA (tRNA) genes and three ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that T. tetragonioides was close to and Sesuvium portulacastrum

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4–512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections