Repurposing of FDA-Approved drugs to predict new inhibitors against key regulatory genes in <i>Mycobacterium tuberculosis</i>

Tuberculosis (TB) disease has become one of the major public health concerns globally, especially in developing countries. Numerous research studies have already been carried out for TB, but we are still struggling for a complete and quick cure for it. The progress of Mycobacterium tuberculosis (MTB) strains resistant to existing drugs makes its cure and control very complicated. Therefore, it is the need of the hour to search for newer and effective drugs that can inhibit an increasing number of putative drug targets. We applied the drug repurposing concept to identify promising FDA-approved drugs against five key-regulatory genes (FurB, IdeR, KstR, MosR, and RegX3) of the MTB. The FDA drugs were virtually screened using a structure-based approach by GOLD versions 5.2, and subjected to rigid docking followed by an induced-fit docking algorithm to enhance the accuracy and prioritize drugs for repurposing. We found 11 candidate drugs (including ZINC03871613, ZINC03871614, ZINC03871615 as top scorer candidate drugs) that were frequently present within the top 20 GoldScore ranks and showed promising results. Furthermore, molecular dynamics simulation was performed to monitor the effect of the top scorer drugs on the structural stability of all the five targets, indicating that inhibitors preferentially bind to the active site of the targets. This work suggests that these known FDA-approved drugs open new application domains in the form of anti-tuberculosis agents.

     

Influence of cold plasma treatment on insecticidal properties of wheat seeds against red flour beetles

For the long-term fortification of warehoused crops, the insecticidal impact of cold plasma treated wheat seeds against red flour beetles are studied. In this study, the gain weight loss, mortality and repellency tests of cold plasma treated seeds are investigated and statistical analysis is carried out by SPSS software. Cold plasma treatment is carried out at 800 V for 1 and 4 min. The results show that the minimum grain weight loss is observed in plasma treated seeds as compared to controlled seeds. It is also observed that the mortality rate is minimum in the controlled seed while maximum at 4 min plasma treatment. Similarly, the repellent effect has a very small variation as compared to the controlled seed for Tribolium Castaneum. Therefore, plasma treatment can be considered as a practical and effective method for seed protection against red floor beetles particularly during long-term storage by controlling the insecticidal effects.     

固态维电器的动态功耗和设计考量

介绍 对于低电压信号或低功率切换应用,具备MOSFET输出的光学隔离固态继电器(SSR,solid state Relay)可以比传统机电式继电器(EMR,Electro-Mechanical Relay)带来几个重要优势,工程师在使用这类继电器时面临的一个主要挑战是如何决定并找出继电器封装内可以承受的最大动态和静态功率,工作频率基本上会对整体功耗带来最高限制,因此非常重要的一点是,必须精确计算动态和静态功耗以保证不会超出固态继电器规格所允许的最大功率,最后我们也会提供固态继电器可以在终端应用取得优势的应用范例.     

Computational single phase comparative study of inclined MHD in a Powell–Eyring nanofluid

In this study, the heat transfer and entropy of transient non-Newtonian Powell–Eyring nanofluid flow is studied. The nanofluid flows over a stretched flat surface, moving nonuniformly. The flow and heat transfer properties are analyzed subject to a convective heated slippery surface. This study also examined the thermal radiation, nanoparticle shapes, inclined magnetic field (B), and joule heating. The governing equations of flow are formulated in partial differential equations (PDEs). A numerical technique utilizes the Keller Box Method to find the similarity solution of the reduced ordinary differential equations, converted from PDEs by using an appropriate transformation. Two different nanofluids, copper–methanol (Cu–MeOH) and silicon carbide–methanol (SiC–MeOH), are considered in the analysis. Significant results of various parameters for the flow, heat, Skin friction (C_f), Nusselt number (Nu), and entropy analysis are described graphically. This study's remarkable finding is that the thermal conductivity in Powell–Eyring phenomena gradually increases compared to the conventional fluid. The Cu–MeOH based nanofluid is found to be a superior thermal conductor instead of the SiC–MeOH based nanofluid. The entropy of the system exaggerates with the incorporation of nanoparticle volume fraction $\varphi$, thermal radiation Nr, and material parameter $\mathrm{\Delta }$. It is found that the slip parameters work as a retarded force to the system and decrease the system's entropy.     

PREPARATION OF CLOVE BUDS DEODORIZED AQUEOUS EXTRACT (CDAE) AND EVALUATION OF ITS POTENTIAL TO IMPROVE OXIDATIVE STABILITY OF CHICKEN MEATBALLS IN COMPARISON TO SYNTHETIC AND NATURAL FOOD ANTIOXIDANTS

ABSTRACT

Antioxidative properties of prepared clove buds deodorized aqueous extract (CDAE) in chicken meatballs are studied. Total phenolic and flavonoid contents were found to be 271.9 ± 12.0 mg gallic acid equivalent per gram and 161.6 ± 7.7 mg rutin equivalent per gram CDAE, respectively. Chicken meatball samples were: (1) C (control, i.e., without CDAE), and those supplemented with 200 ppm of; (2) T1 (CDAE); (3) T2 (ascorbic acid); and (4) T3 (butylated hydroxyanisole [BHA] : butylated hydroxytoluene [BHT] = 1:1). Oxidative stability was assessed by measuring peroxide value (PV) and 2‐thiobarbituric acid reactive substances (TBARS) besides determination of color and sensory acceptability, over 12 days of chilled storage (8 ± 1C). All the treated samples showed higher induction period as well as lower PV and TBARS values than “C” throughout 12 days of storage (*P < 0.05). Color analysis showed that CDAE greatly improved redness of meatballs as compared with ascorbic acid and BHA‐BHT (*P < 0.05). Meanwhile, hedonic test indicated that treatment T1 did not affect sensory acceptability of chicken meatballs for all the tested attributes (color, aroma, taste, texture and overall acceptance) (*P > 0.05) up to comparable extent with T2 and T3.

PRACTICAL APPLICATIONS

The study provides a valuable method for the preparation of meatballs by replacing harmful synthetic antioxidants with natural ones with promising antioxidant and shelf‐life potential besides maintaining sensory attributes. This adaptation may result in massively enhanced consumption of these meatballs with disease‐preventive and health‐promoting effects. The main hurdle in commercialization of spicy meatballs is the pungent smell of spices as well as use of toxic organic solvents for extraction. The problem has been overcome by developing a method for the preparation of deodorized extracts in aqueous medium, which may significantly enhance the commercialization potential of meatballs and meatball‐based functional foods.     

Eco-friendly green synthesis of silver nanoparticles and their potential applications as antioxidant and anticancer agents

Abstract

Eco-friendly green synthesis of nanoparticles using medicinal plants gained immense importance due to its potential therapeutic uses. In the current study, silver nanoparticles (AgNPs) were synthesized using water extract of Jurinea dolomiaea leaf and root at room temperature. MTT assay was used to study anticancer potential of AgNPs against cervical cancer cell line (HeLa), breast cancer cell lines (MCF-7), and mouse embryonic fibroblast (NIH-3 T3) cell line for toxicity evaluation. The antioxidant potential was evaluated using stable DPPH radicals. In addition, the apoptotic nuclear changes prompted by AgNPs in more susceptible HeLa cells were observed using fluorescence microscope through DAPI and PI staining. Physiochemical properties of biosynthesized AgNPs were characterized using various techniques. AgNPs were formed in very short time and UV–vis spectra showed characteristic absorption peak of AgNPs. SEM and TEM showed spherical shape of AgNPs and XRD revealed their crystalline nature. EDX analysis revealed high percentage of silver in green synthesized AgNPs. FTIR analysis indicated involvement of secondary metabolites in fabrication of AgNPs. In vitro cytotoxic and antioxidant study revealed that herb and biosynthesized AgNPs exhibited significant dose-dependent and time-dependent anticancer and antioxidant potential. Furthermore, study on normal cell line and microscopic analysis of apoptosis revealed that AgNPs exhibited good safety profile as compared to cisplatin and induces significant apoptosis effect. Based on the current findings, it is strongly believe that use of J. dolomiaea offers large scale production of biocompatible AgNPs that can be used as alternative anticancer agents against cancer cell lines tested.     

Effect of fluxing additive on sintering temperature, microstructure and properties of BaTiO3

Various fluxing materials are added to technical ceramics in an attempt to lower their sintering temperatures and make their processing economical. The effect of 0·3?wt% Li₂CO₃ addition on the phase, microstructure, phase transition temperatures and dielectric properties of BaTiO₃ was investigated in the present study. The addition of 0·3?wt% Li₂CO₃ was observed to lower the optimum sintering temperature by ??200°C with no second phase formation and cause a five-fold reduction in grain size. Rhombohedral-to-orthorhombic and tetragonal-to-cubic phase transitions at the expected temperatures were evident from the Raman spectra, but the orthorhombic-to-tetragonal phase transition was not clearly discernible. The persistence of various phase(s) at higher temperatures in the flux-added materials indicated that the phase transitions occurred relatively slowly. A decrease in dielectric constant of Li₂O-added BaTiO₃ in comparison to pure BaTiO₃ may be due to the diminished dielectric polarizability of Li^?+? in comparison to Ba^2?+?.     

Bioactivity,in-vitro corrosion behavior,and antibacterial activity of silver–zeolites doped hydroxyapatite coating on magnesium alloy

Mg-based alloys received significant attention for temporary implant applications while, their applications have been limited by high degradation rate. Therefore, silver–zeolite doped hydroxyapatite (Ag-Zeo-HAp) coating was synthesized on TiO₂-coated Mg alloy by physical vapour deposition (PVD) assisted electrodeposition technique to decrease the degradation rate of Mg alloy. X-ray diffraction (XRD) analysis and field emission scanning electron microscopy (FE-SEM) images showed the formation of a uniform and compact layer of Ag-Zeo-HAp with a thickness of 15 μm on the TiO₂ film with a thickness of 1 μm. The potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) tests indicated that corrosion resistance of Mg-Ca alloy was considerably increased by the Ag-Zeo-HAp coating. The bioactivity test in the simulated body fluid (SBF) solution showed that a dense and homogeneous bonelike apatite layer was formed on the Ag-Zeo-HAp surface after 14 d. Investigation of antibacterial activity via disk diffusion and spread plate methods showed that the Ag-Zeo-HAp coating had a significantly larger inhibition zone (3.86 mm) towards Escherichia coli (E. coli) compared with the TiO₂-coated Mg alloy (2.61 mm). The Ag-Zeo-HAp coating showed high antibacterial performance, good bioactivity, and high corrosion resistance which make it a perfect coating material for biomedical applications.     

SiC_p及Al_2O_(3w)增强铸态混杂金属基复合材料的疲劳裂纹扩展机理(英文)

研究了一种SiCp及Al2O3w增强铸态混杂金属基复合材料(MMC)的疲劳裂纹扩展(FCG)机理,同时对比研究了Al2O3w增强铸态金属基复合材料和铸态铝合金的疲劳裂纹扩展机理。在研究近临界和裂纹稳定扩展区域的疲劳裂纹扩展(FCG)机理时,发现混杂MMC的临界应力强度因子?Kth值高于其他两种材料的?Kth值,说明应力强度因子?K值较低时混杂MMC可以更好地抵抗裂纹扩展。随着?K值的降低,两种MMC在近临界区域显示出相似的FCG机理,即主要由增强相–基体界面的剥离控制,随后由铝基体中空隙的形核与合并控制;在裂纹稳定或中等扩展区域,?K值较高时FCG除了受界面上周期性裂纹扩展引起的增强相–基体界面剥离的影响之外,还显著受到铝基体中疲劳条带的影响。此外,在高?K值下,因为局部失稳断裂机制,可见铝基体中空隙的形核与合并以及SiCp和Al2O3w中的穿晶断裂。对于铸态铝合金,在低?K值下,FCG主要受空隙的形核与合并所控制;在高?K值下,FCG主要受铝晶粒的疲劳条带控制,随后受Si团簇中空隙的形核与合并控制。