Recent development and strategies towards target interactions: Synthesis, characterization and in silico analysis of benzimidazole based thiadiazole as potential anti-Alzheimer agents.

In the current research study, we aim to design and synthesize highly potent hybrid analogs of benzimidazole derived thiadiazole based Schiff base derivatives which can combat the cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) accountable for developing Alzheimer's disease. In this context, we have synthesized 15 analogs of benzimidazole based thiadiazole derivatives, which were subsequently confirmed through spectroscopic techniques including 1H NMR, 13C NMR and HREI-MS. Biological investigation of all the analogs revealed their varied acetylcholinesterase inhibitory potency covering a range between 3.20 ± 0.10 µM to 20.50 ± 0.20 µM as well as butyrylcholinesterase inhibitory potential with a range of 4.30 ± 0.50 µM to 20.70 ± 0.50 µM when compared with the standard drug Donepezil having IC50 = 6.70 ± 0.20 µM for AChE and 7.90 ± 0.10 µM for BuChE. The promising inhibition by the analogs was evaluated in SAR analysis, where analog-1 (IC50 = 3.20 ± 0.10 µM for AChE and 4.30 ± 0.50 µM for BuChE), analog-4 (IC50 = 4.30 ± 0.30 µM for AChE and 5.50 ± 0.20 µM for BuChE) and analog-5 (IC50 = 4.10 ± 0.30 µM for AChE and 4.60 ± 0.40 µM for BuChE) were found as the lead candidates. Moreover, molecular docking and ADME analysis were conducted to explore the better binding interactions and drugs likeness respectively.

Investigation of novel bis-thiadiazole bearing schiff base derivatives as effective inhibitors of thymidine phosphorylase: Synthesis, in vitro bioactivity and molecular docking study.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It is crucial for the development, invasion and metastasis of tumors as well as angiogenesis. In our current research, we examine how structurally changing bis-thiadiazole bearing bis-schiff bases affects their ability to inhibit TP. Through the oxidative cyclization of pyridine-based bis-thiosemicarbazone with iodine, a series of fourteen analogs of bis-thiadiazole-based bis-imines with pyridine moiety were developed. Newly synthesized scaffolds were assessed in vitro for their thymidine phosphorylase inhibitory potential and showed moderate to good inhibition profile. Eleven scaffolds such as 4a-4d,4f-4 h and 4j-4 m were discovered to be more effective than standard drug at inhibiting the thymidine phosphorylase enzyme with IC50 values of 1.16 ± 1.20, 1.77 ± 1.10, 2.48 ± 1.30, 12.54 ± 1.60, 14.63 ± 1.70, 15.53 ± 1.80, 17.47 ± 1.70, 18.98 ± 1.70, 19.53 ± 1.50, 22.73 ± 2.40 and 24.87 ± 2.80 respectively, while remaining three analogs such as 4n, 4i and 4ewere found to be more potent, but they were less potent than the standard drug. All analogs underwent SAR studies based on the pattern of substitutions around the aryl part of the bis-thiadiazole skeleton. The most active analogs in the synthesized series were then molecular docking study performed to investigate their interactions of active part of enzyme. The results showed that remarkable interactions were exhibited by these analogs with the targeted enzymes active sites. Furthermore, to confirm the structure of synthesized analogs by employing spectroscopic tools such as HREI-MS and NMR.

Financial performance of China's listed firms in presence of coronavirus: Evidence from corporate culture and corporate social responsibility.

Motivated from the shortage of the existing research studies on impacts of dangerously contagious diseases on firms' financial performance, this study sheds light on the impacts of Coronavirus (Covid-19) outbreak on financial performance upon on the quarterly data of 126 Chinese listed firms across 16 industries. Overall, the Covid-19 outbreak reduced Chinese listed firms' financial performance proxied by the revenue growth rate, ROA, ROE, and asset turnover. This outbreak's negative effects on Chinese firms' profitability were much smaller than that on their revenue growth rates. While this outbreak's negative effects on financial performance of Chinese listed firms were bigger for those that were seriously affected by this pandemic like airlines, travel, and entertainment (ATE), this pandemic's effects were positive for the medicine industry. In the meanwhile, Chinese listed firms that located in high-risk regions suffered a bigger financial loss during the outbreak, and especially there was a strong Hubei effect. The corporate culture and CSR moderated the inverse relationship between this outbreak and Chinese firms' financial performance. Findings of this study contribute to enrich the existing literature on impacts of the Covid-19 outbreak on firms' financial performance worldwide and suggest helpful practical and theoretical implications.

Chemical synthesis of a library of natural product-like derivatives based on pinnaic acid and initial evaluation of their anti-cancer activity.

Halichlorine and pinnaic acid have been shown previously to be potent inhibitors of the inflammatory enzymes cPLA2 and VCAM-1 and have also demonstrated some anti-cancer activity. They possess an almost identical azaspirocyclic core consisting of a unique 3-dimensional geometry with four stereocentres, making them compounds of interest for further study to reveal any bioactivity not yet discovered. The azaspirocyclic core was synthesised from an established protocol, from which a small library of novel analogues were synthesised and tested for activity against two cancer cell lines, HeLa and CaCo-2, along with the non-cancerous cell line HaCaT. Eleven compounds were found to be selective for CaCo-2 cells.

Exploration on the coordinated development of urbanization and the eco-environmental system in central China.

Scientific evaluation of the interaction between urbanization and the eco-environmental system in Central China is of great significance. To optimizing the quality of urbanization and improving the eco-environmental state. As a case study of Central China, this research attempts to build a set of analytical systems to realize the integrated deconstruction from analyzing comprehensive evaluation indexes, quantification of coupling coordination, spatiotemporal evolution traits, decoupling path exploration to influential factor analysis. It tries to clarify the differences between cities, identify problematic areas, and propose targeted improvement measures. The outcomes show that the urbanization level of the cities in Central China has been improved significantly. In contrast, their eco-environmental levels are fluctuating, with the growth rate lower than that of urbanization. The coordination level between the two systems is rising, changing from primary dysfunction to intermediate coordination. The coordination level is characterized by obvious spatial association dominated by Types H-H and L-L and ever-increasing agglomeration. The decoupling between the two systems only falls into two types: strong decoupling and relative decoupling with expansion, indicating a negative effect between them. There is a problem regarding negative urbanization development. The factors including energy consumption, investment in fixed assets, opening to the outside world, technological progress, and government management capabilities all have an impact on the coordination of the two with divergent significances.

Extracellular microRNAs: key players to explore the outcomes of in vitro fertilization.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown. METHODS: This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS. RESULTS: The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p < 0.001). Our results showed that miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 in NOR patients with a sensitivity of 80% and specificity of 71%, (AUC = [0.753 (0.651; 0.855)], p = 0.001). For clinical pregnancy outcome prediction, FF miRNA-21 exhibited high sensitivity (74.8%) and specificity (83.7%) with the AUC value of 0.774 (0.682; 0.865). CONCLUSION: Conclusively, our results provide evidence that miR-7-5p, miR-378-3p, miR-224, miR-212-3p were a differentially high expression in normo-androgenic PCOS patients than NOR patients. While miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 (p = 0.001). The expression level of FF miR-212-3p was significantly related to the probability of embryos to develop into a high-quality blastocyst in patients with normal ovarian reserve.

Melatonin levels and microRNA (miRNA) relative expression profile in the follicular ambient microenvironment in patients undergoing in vitro fertilization process.

PURPOSE: Intrafollicular fluid (IFF) melatonin plays a decisive role in maintaining granulosa cells' DNA integrity and protects them against apoptosis. It reduces oxidative stress and improves the oocyte quality with a higher fertilization rate. METHOD: This prospective study investigated the antioxidant property of IFF melatonin and its impact on IVF outcome parameters. We also explored the relative expression of five microRNAs (miR-663b, miR-320a, miR-766-3p, miR-132-3p, miR-16-5p) and levels of cell-free DNA (cfDNA) by real-time PCR in unexplained infertile patients. We collected 425 follicular fluid (FF) samples containing mature oocytes from 295 patients undergoing IVF. RESULTS: Patients were subgrouped based on IFF melatonin concentration (group A ≤ 30 pg/mL, group B > 70 to ≤ 110 pg/mL, group C > 111 to ≤ 385 pg/mL). Our results showed that patients with ≤ 30 pg/mL IFF melatonin levels have significantly higher oxidative stress markers, cfDNA levels, and lower relative expression of miR-663b, miR-320a, miR-766-3p, miR-132-3p, and miR-16-5p compared to other subgroups (p < 0.001). Similarly, they have a low fertilization rate and a reduced number of high-quality day 3 embryos. CONCLUSION: Findings suggest that the therapeutic use of melatonin produces a considerable rise in the number of mature oocytes retrieved, fertilization rate, and good-quality embryo selection. Furthermore, miRNA signature enhances the quality of embryo selection, thus, may allow us to classify them as non-invasive biomarkers to identify good-quality embryos.

Evaluating the impact of double dose vaccination on SARS-CoV-2 spread through optimal control analysis.

This paper presents a new nonlinear epidemic model for the spread of SARS-CoV-2 that incorporates the effect of double dose vaccination. The model is analyzed using qualitative, stability, and sensitivity analysis techniques to investigate the impact of vaccination on the spread of the virus. We derive the basic reproduction number and perform stability analysis of the disease-free and endemic equilibrium points. The model is also subjected to sensitivity analysis to identify the most influential model parameters affecting the disease dynamics. The values of the parameters are estimated with the help of the least square curve fitting tools. Finally, the model is simulated numerically to assess the effectiveness of various control strategies, including vaccination and quarantine, in reducing the spread of the virus. Optimal control techniques are employed to determine the optimal allocation of resources for implementing control measures. Our results suggest that increasing the vaccination coverage, adherence to quarantine measures, and resource allocation are effective strategies for controlling the epidemic. The study provides valuable insights into the dynamics of the pandemic and offers guidance for policymakers in formulating effective control measures.

Will advancement in technologies bring fear and damage human employment? Evidence from China's manufacturing industry.

Advancement in technologies such as robotic industries and artificial intelligence bring fear among human being that jobs will be substituted by robots. Base on the panel data of 28 China's manufacturing industries, this research analyzed the impact of technical progress bias on employment. First, we calculate the technical progress bias index of 28 industries base on the stochastic frontier model with transcendental logarithm function found 16 industries were toward the skilled labor while the remaining 12 industries were toward the unskilled labor. Second, the empirical results show that technical progress bias has a positive impact on the total manufacturing employment and significant positive effect on the unskilled labor, while no significant impact on skilled labor employment. Third, the threshold effect test proves that if taking industry value-added per capita or R&D capital stock as threshold variable, the threshold about the impact exist, making the impact on skilled labor was insignificant.

Facile benzothiazole-triazole based thiazole derivatives as novel thymidine phosphorylase and α-glucosidase inhibitors: Experimental and computational approaches.

The present study reports the new thiazole (A-L) derivatives based on benzothiazole fused triazole which were synthesized and assessed against thymidine phosphorylase and α-glucosidase enzymes. Several compounds with the same basic structure but different substituents were found to have high activity against the targeted enzymes, while others with the same basic skeleton but different substituents were found to have medium to low activity among the members of tested series. These analogs showed a varied range of inhibition in both case thymidine phosphorylase and alpha glucosidase, A (IC50 = 7.20 ± 0.30 µM and IC50 = 1.30 ± 0.70 µM), B (IC50 = 8.80 ± 0.10 µM and IC50 = 2.10 ± 0.30 µM), C (IC50 = 8.90 ± 0.40 µM and IC50 = 3.20 ± 0.20 µM) and thiazole containing analogs such as G (IC50 = 11.10 ± 0.20 µM and IC50 = 7.80 ± 0.20 µM) and H (IC50 = 12.30 ± 0.30 µM and IC50 = 6.30 ± 0.20 µM). When compared with standard drugs 7-Deazaxanthine, 7DX (IC50 = 10.60 ± 0.50 µM) and acarbose (IC50 = 4.30 ± 0.30 µM) respectively. These analogs were also subjected to molecular docking studies which indicated the binding interaction of molecules with active sites of the enzyme and strengthen the drug profile of these compounds. ADMET studies also predict the drug-like properties of these compounds, with no violations of drug likeness rules.

Identification of novel benzothiazole-thiadiazole-based thiazolidinone derivative: in vitro and in silico approaches to develop promising anti-Alzheimer's agents.

Aim: The present study describes benzothiazole derived thiazolidinone based thiadiazole derivatives (1-16) as anti-Alzheimer agents. Materials & methods: Synthesis of benzothiazole derived thiazolidinone based thiadiazole derivatives was achieved using the benzothiazole bearing 2-amine moiety. These synthesized compounds were confirmed via spectroscopic techniques (1H NMR, 13C NMR and HREI-MS). These compounds were biologically evaluated for their anti-Alzheimer potential. Binding interactions with proteins and drug likeness of the analogs were explored through molecular docking and ADMET analysis, respectively. In the novel series, compound-3 emerged as the most potent inhibitor when compared with other derivatives of the series. Conclusion: The present study provides potent anti-Alzheimer's agents that can be further optimized to discover novel anti-Alzheimer's drugs.

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In vitro enzymatic, in silico ADME and molecular docking based analysis for the identification of novel bis-indole containing triazine-thiazole hybrids derivatives as promising urease inhibitors.

The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including 1H NMR, 13C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC50 = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC50 = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure-activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC50 = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC50 = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.

Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives.

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that target drug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and -CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.

Functional outcome of primary hamstring anterior cruciate ligament reconstruction in patients with different body mass index classes.

PURPOSE: We compared functional outcomes after primary hamstring-graft anterior cruciate ligament (ACL) reconstruction in patients with different body mass index (BMI) classes. METHODS: Functional outcomes after ACL reconstruction were measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Lysholm score. The procedures were carried out by a single surgeon between 2001 and 2009 in 2 groups of patients with different BMI classes: a normal-BMI group (BMI 18.5 to 24.9) and a high-BMI group (BMI ≥ 25), with a minimum of 2 years' follow-up. Rolimeter readings for ligament laxity as well as complications between the 2 groups were also analyzed. RESULTS: A total of 92 patients were reviewed, with the normal-BMI group consisting of 49 patients, whereas there were 43 patients in the high-BMI group. There were no significant differences between the groups in any of the preoperative and postoperative scores or ligament laxity. Both groups showed comparable clinically significant improvement in their postoperative scores compared with their preoperative scores. Patients in the high-BMI group had a slightly increased postoperative complication rate when compared with the normal-BMI group. CONCLUSIONS: Primary hamstring ACL reconstruction is an effective treatment option in patients irrespective of preoperative BMI. High BMI does not adversely affect functional outcomes as measured by the KOOS and Lysholm scores up to and at 2 years postoperatively, and these patients benefit in a manner comparable to that of patients with normal BMI. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Ecological environment pressure state and response system for coupling coordinate development: an application on china data.

This research aims to develop an ecological carrying capacity index for the ecological environment under the principle of the pressure-state-response framework model and discusses the coupling coordination of ecological environment pressure, state, and response system of the urban region in china from 2011 to 2020. Furthermore, predicated the degree of security warning for each year while establishing the ecological carrying capacity index and the urban ecological coupling model. Results specify that the coordination degree of urban ecological development in Nanchang, Jiangxi has been improved year by year, the ecological carrying capacity security index shows an upward tendency from the overall view, and the security warning degree rises from comparative insecurity to comparative security. The analysis demonstrates that in the process of national ecological civilization construction demonstration zone construction, the ecological resources and environmental policies adopted by Nanchang city have played a great role in promoting ecological security. However, the ecological security index in Nanchang is still below 0.6, far from the high-security level (0.77), and the government and the public still need to do a lot to improve ecological security.

Transition to a low-CO2 emissions economy: China government policy for early-stage green finance.

The popularity of green economy as an innovative technique and financial mechanism has soared as a result of this exchange, the gross domestic product (GDP); transition economy (TE); CO2 emissions; human capital (HC); Government Fund Strategy (GFS); green finance (GF) play a very important role. When it comes to advancing genetic civilization, China's achievements in the field of green money have become firm proof of the country's progress. China has come to terms with the fact that it cannot continue on its current path of promoting monetary development at the expense of the environment, both for its own people and for the sake of the global community. The country has prioritized environmental concerns over equality with others through economic, political, social, and other factors. Furthermore, in order to accomplish the enormous goal, China's cross-country coal use must be covered to allow it to peak before 2020, and fossil fuel byproducts must peak before 2030. This article argues that China's "green drive" is a cause for optimism and concludes by arguing that the top 2030 goal for fossil fuel byproducts is ambitious but doable.

What are the impetuses Behind E-health applications' self-management services' ongoing adoption by health community participants?

Over the past 20 years, the identification of interventions related to healthcare management has been greatly facilitated by improvements in the well-being and health of the entire population. However, regardless of the positive developments in smart health applications and e-health research, there are two important gaps, (1) the role of gamification variables in the continued use of eHealth applications has not been adequately assessed, and (2) the extent to which people's perception of the continued use of e-health applications is encouraged through habit. Customers and companies can derive considerable value from exploring E-Health applications' health self-management services. Accordingly, estimating such services' ongoing adoption by customers is aimed for in this research, with habits, intrinsic and extrinsic variables incorporated into a study model which is then tested. This paper examined perceived autonomy, perceived competence, perceived relatedness has positively related to enjoyment and habit. Reward has positively related to perceived autonomy and continued to use. Enjoyment and Habit have positively associated with the decision to continue to use in e-Health Apps. 269 individuals who have used Chinese e-health applications comprised the data collection sample, being reached via an online questionnaire. Data analysis was undertaken using Partial Least Squares Structural Equation Modelling (PLS-SEM). It was found that the ongoing adoption of e-health self-management services was perpetuated to a greater extent by intrinsic variables; in terms of strategizing for companies' e-services, the results can inform this process.

Optimization of investment strategies through machine learning.

The main objective of this research is to develop a sustainable stock quantitative investing model based on Machine Learning and Economic Value-Added techniques for optimizing investment strategies. Quantitative stock selection and algorithmic trading are the two features of the model. Principal component analysis and economic value-added criteria are used in quantitative stock model for efficiently stocks selection, which may repeatedly select valuable stocks. Machine learning techniques such as Moving Average Convergence, Stochastic Indicators and Long-Short Term Memory are used in algorithmic trading. One of the first attempts, the Economic Value-Added indicators are used to appraise stocks in this study. Furthermore, the application of EVA in stock selection is exposed. Illustration of the proposed model has been done on United States stock market and finding shows that Long-Short Term Memory (LSTM) networks can more accurately forecast future stock values. The proposed strategy is feasible in all market situations, with a return that is significantly larger than the market return. As a result, the proposed approach can not only assist the market in returning to rational investing, but also assist investors in obtaining significant returns that are both realistic and valuable.

A machine learning-based Biding price optimization algorithm approach.

Trading companies of used product market are struggling to gain customers attentaion and to sell the products. The aim of this research is to develop a mechanism that can maximize the sale of products while considering profit implications. The literature review classifies the procurement mechanism. Given the limited-supply nature, that also includes unpredictable quality levels and a procurement mechanism that perceives the company offering prices to suppliers on a single-item basis. The academic literature has not covered such a mechanism. Techniques like those that improve the required bidding strategy are reviewed and considered fit to be included in the support tool as the procedures intention to maximize an objective function depending on the bidding price and contain the probability of winning the auction and the profit made from the proceeding, the motivation laid on the approach that predicts the probability. It is determined that this assembles a Response to Reverse Request for Quotation that meets the assumptions of a First-Price Sealed-Bid(FPSD) auction that potentially includes a hidden reservation price.

Does globalization and ecological footprint in OECD lead to national happiness.

This study examines the relationship between globalization, ecological footprint, innovation, and subjective wellbeing in the form of happiness, using a comprehensive assessment of OECD countries from 2008 to 2020. The study employs FGLS, Quantile, and Bootstrap Quantile regression estimation to investigate the quadratic effects of globalization, ecological footprint, and the moderating effect of innovation while controlling for renewable energy and population density. Happiness is a multidisciplinary subject, and this study focuses on the economic dimensions of happiness. The findings reveal a nonlinear relationship between ecological footprint and globalization, with negative effects on subjective wellbeing at high levels of ecological footprint and globalization. However, the moderating effect of innovation mitigates these adverse effects, indicating that innovation can help to offset the detrimental impacts of ecological footprint and globalization on subjective wellbeing. The study's implications are significant for policymakers promoting sustainable economic growth while enhancing subjective wellbeing. The findings highlight the importance of investing in innovation and sustainable development to promote subjective wellbeing in the face of increasing ecological footprint and globalization. Additionally, this research contributes to the multidisciplinary understanding of happiness and provides valuable insights for future research in this area.