Explore the vast range of titles available.

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.

Although the formation of metal–carbon σ bonds is a fundamental principle in organometallic chemistry, the direct bonding of one organic molecule with one metal center to generate more than two metal–carbon σ bonds remains a challenge. Herein, we report an aromaticity-driven method whereby multiyne chains are used to construct three metal–carbon σ bonds in a one-pot reaction under mild conditions. In this method, multiyne chains act as ligand precursors capable of chelating an osmium center to yield planar metallapolycycles, which exhibit aromaticity and good stability. The direct assembly of various multiyne chains with commercially available metal complexes or even simple metal salts provides a convenient and efficient strategy for constructing all carbon-ligated chelates on the gram scale. Metal-carbon σ bonds mark the basis of organometallic chemistry, but the formation of multiple such bonds between single organic and metal entities remains a challenge. Here, the authors report a one-pot aromaticity-driven method to construct osmium-based multidentate complexes containing three metal-carbon σ bonds from multiyn chains.

Polydentate complexes containing combinations of nitrogen and carbon (N and C) ligating atoms are among the most fundamental and ubiquitous molecules in coordination chemistry, yet the formation of such complexes with planar high-coordinate N/C sites remains challenging. Herein, we demonstrate an efficient route to access related complexes with tetradentate CCCN and pentadentate CCCCN and NCCCN cores by successive modification of the coordinating atoms in complexes with a CCCC core. Combined experimental and computational studies reveal that the rich reactivity of metal-carbon bonds and the inherent aromaticity of the metallacyclic skeletons play key roles in these transformations. This strategy addresses the paucity of synthetic approaches to mixed N/C planar pentadentate chelating species and provides valuable insights into the synthesis of carbon-based high-coordinate complexes. Furthermore, the resulting complexes are the examples of organometallic species with combined photoacoustic, photothermal, and sonodynamic properties, which makes them promising for application in related areas. Coordination complexes based on polydentate ligands that contain both nitrogen and carbon ligating atoms are ubiquitous, but design of those with planar cores remains challenging. Here the authors show that complexes with planar CCCN, CCCCN and NCCCN cores can be accessed by modification of the coordinating atoms in CCCC core complexes.

Glucose and lipid metabolism disorder in diabetes mellitus often causes damage to multiple tissues and organs. Diabetes mellitus is beneficially affected by quercetin. However, its concrete mechanisms are yet to be fully elucidated. In our study, diabetes was induced in Sprague-Dawley rats by STZ injection. The rats were randomly divided into normal control, diabetic model, low-dose quercetin treatment, high-dose quercetin treatment, and pioglitazone treatment groups. Fasting blood glucose was collected to evaluate diabetes. Immunohistochemistry and fluorometric assay were performed to explore SIRT1. Akt levels were measured through immunoprecipitation and Western blot. After 12 weeks of quercetin treatment, the biochemical parameters of glucose and lipid metabolism improved to varying degrees. Hepatic histomorphological injury was alleviated, and hepatic glycogen content was increased. The expression and activity of hepatic SIRT1 were enhanced, and Akt was activated by phosphorylation and deacetylation. These results suggested that the beneficial effects of quercetin on glucose and lipid metabolism disorder are probably associated with the upregulated activity and protein level of SIRT1 and its influence on Akt signaling pathway. Hence, quercetin shows potential for the treatment of glucose and lipid metabolism disorder in diabetes mellitus.

Sophora flavescens is a regularly used traditional Chinese medicine. In an attempt to discover adequate active agents, the isoprenoid flavonoids from S. flavescens were further investigated. In this work, two new compounds (1–2, kurarinol A-B) together with 26 known ones (3–28) were isolated and elucidated on the basis of extensive NMR, UV and MS analyses. Furthermore, the antioxidant activity of all constituents was assessed through ABTS, PTIO and DPPH methodologies and also were evaluated for cytotoxic activity by three tumor cell lines (HepG2, A549 and MCF7) and one human normal cell line (LO2 cells). As a result, a multitude of components revealed significant inhibitory activity. In particular, compound 1–2 (kurarinol A-B), two new flavanonols derivatives, exhibited the most potent ABTS inhibitory activity with IC50 of 1.21 µg/mL and 1.81 µg/mL, respectively. Meanwhile, the new compound 1 demonstrated remarkable cytotoxicity against three cancer cells lines with IC50 values ranging from 7.50–10.55 μM but showed little effect on the normal cell. The two new isoprenoid flavonoids could be promising antioxidant and anti-tumor nature agents.

Constitutive activation of TGF-β signaling pathway is a well-documented mechanism responsible for the bone metastasis of prostate cancer (PCa). MicroRNAs (miRNAs) have been reported to be crucial for the activation of TGF-β signaling via targeting downstream components of TGF-β signaling pathway. Here, we report that miR-19a-3p is downregulated in bone metastatic PCa tissues and cells. Upregulation of miR-19a-3p suppresses invasion, migration in vitro and inhibits bone metastasis in vivo in PCa cells. Conversely, silencing miR-19a-3p yields the opposite effect. Our results further demonstrate that miR-19a-3p inhibits invasion and migration abilities of PCa cells via targeting downstream effectors of TGF-β signaling, SMAD2 and SMAD4, resulting in the inactivation of TGF-β signaling. Therefore, our results uncover a novel mechanistic understanding of miR-19a-3p-induced suppressive role in bone metastasis of PCa, which will facilitate the development of effective cancer therapy methods against PCa.

Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases globally. Hepatic stellate cells (HSCs) are the major effector cells of liver fibrosis. HSCs contain abundant lipid droplets (LDs) in their cytoplasm during quiescence. Perilipin 5 (PLIN 5) is a LD surface‐associated protein that plays a crucial role in lipid homeostasis. However, little is known about the role of PLIN 5 in HSC activation. Methods PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection. At the same time, PLIN 5 gene knockout mice were constructed and fed with a high‐fat diet (HFD) for 20 weeks to study the role of PLIN 5 in NAFLD. The corresponding reagent kits were used to measure TG, GSH, Caspase 3 activity, ATP level, and mitochondrial DNA copy number. Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC‐MS/MS. AMPK, mitochondrial function, cell proliferation, and apoptosis‐related genes and proteins were detected by western blotting and qPCR. Results Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria, inhibition of cell proliferation, and a significant increase in cell apoptosis through AMPK activation. In addition, compared with the HFD‐fed C57BL/6J mice, PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition, decreased LD abundance and size, and reduced liver fibrosis. Conclusion These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD. PLIN 5 regulation mechanisms in HSC Activation and fibrosis progression in NAFLD.

At present, several studies have assessed the association between ERCC6 rs2228526 polymorphism and the risk of cancer. However, the association remained controversial. To provide a more accurate estimate on the association, we performed a meta-analysis search of case-control studies on the associations of ERCC6 rs2228526 with susceptibility to cancer. PubMed, Embase, Google Scholar, Wanfang database, and Chinese National Knowledge Infrastructure databases (CNKI) China Biological Medicine Database (CBM) (up to August 2021) were searched to identify eligible studies. The effect summary odds ratio (OR) with 95% confidence intervals (CI) was applied to assay the association between the ERCC6 rs2228526 polymorphism and the risk of cancer. 14 studies included 15 case-control studies which contained 5,856 cases, and 6,387 controls were finally determined as qualified studies for this meta-analysis. Overall, based on current studies, we found significant association between ERCC6 rs2228526 polymorphism and the risk of cancer in four genetic models [the allele model G vs. A: 1.10, (1.03–1.17); the homozygous model GG vs. AA: 1.27, (1.07–1.51); heterozygote model GA vs. AA: 1.08, (1.00–1.17); the dominant model GG + GA vs. AA: 1.10, (1.02–1.19); the recessive model GG vs. GA + AA: 1.22, (1.03–1.45)]. In the stratified analysis based on ethnicity, we found significant association in two genetic models in Asians. Further, significant genetic cancer susceptibility was found under PB control on subgroup analysis by source of control. In addition, no significant association was found in lung cancer and bladder cancer patients in subgroup analyses based on cancer style. This study suggests that the ERCC6 rs2228526 polymorphism may be associated with increased cancer risk.

A micromixer is one of the most significant components in a microfluidic system. A three-dimensional micromixer was developed with advantages of high efficiency, simple fabrication, easy integration, and ease of mass production. The designed principle is based on the concepts of splitting–recombination and chaotic advection. A numerical model of this micromixer was established to characterize the mixing performance for different parameters. A critical Reynolds number (Re) was obtained from the simulation results. When the Re number is smaller than the critical value, the fluid mixing is mainly dependent on the mechanism of splitting–recombination, therefore, the length of the channel capable of complete mixing (complete mixing length) increases as the Re number increases. When the Re number is larger than the critical value, the fluid mixing is dominated by chaotic advection, and the complete mixing length decreases as the Re number increases. For normal fluids, a complete mixing length of 500 µm can be achieved at a very small Re number of 0.007 and increases to 2400 µm as the Re number increases to the critical value of 4.7. As the Re number keep increasing and passes the critical Re number, the complete mixing length continues to descend to 650 µm at the Re number of 66.7. For hard-to-mix fluids (generally referring to fluids with high viscosity and low diffusion coefficient, which are difficult to mix), even though no evidence of strong chaotic advection is presented in the simulation, the micromixer can still achieve a complete mixing length of 2550 µm. The mixing performance of the micromixer was also verified by experiments. The experimental results showed a consistent trend with the numerical simulation results, which both climb upward when the Re number is around 0.007 (flow rate of 0.03 μm/min) to around 10 (flow rate of 50 μm/min), then descend when the Re number is around 13.3 (flow rate of 60 µm/min).