Role of sPD-1 and sPD-Ls in the pathogenesis of connective tissue disease. / sPD-1和sPD-Lsåœ¨ç»“ç¼”ç»„ç»‡ç— å‘ç— æœºåˆ¶ä¸­çš„ä½œç”¨.

Membrane-bound programmed cell death-1 (mPD-1) and membrane-bound programmed cell death-ligands (mPD-Ls) have soluble forms, which are soluble programmed cell death-1 (sPD-1) and soluble programmed cell death-ligands (sPD-Ls) [including soluble programmed cell death-ligand 1 (sPD-L1) and soluble programmed cell death-ligand 2 (sPD-L2)]. sPD-1 and sPD-L2 are mainly produced by alternative splicing isoforms of PD-1 mRNA, while sPD-L1 is produced by matrix metalloproteinases (MMPs) cutting membrane-bound programmed cell death-ligand 1 (mPD-L1). sPD-1 and sPD-Ls play an important role in autoimmune regulation via blocking the mPD-1 /mPD-L1 pathway, while connective tissue disease (CTD) is a kind of disease caused by autoimmune reaction, and abnormal function of mPD-1/mPD-L1 can occur in the occurrence and development of many autoimmune diseases. Therefore, sPD-1 and sPD-Ls play an important role in the pathogenesis of CTD caused by autoimmune reaction via blocking the mPD-1 /mPD-L1 pathway. It is of great practical significance to understand clinical value of sPD-1 and sPD-Ls in various CTDs for improving the quality of life of patients and the underlying mechanism.

Analysis of the binding pattern of NIK inhibitors by computational simulation.

NF-kappaB-Inducing Kinase (NIK) is a key kinase in the activation of the NF-κB non-classical signalling pathway, which has been shown to be over-activated in patients with inflammatory diseases, immune disorders and malignancies and solid tumours inducing activation of the NF-κB non-classical signalling pathway. The design of ATP-competitive small molecule inhibitors against NIK has been a hot topic in the last decade, and many efficient NIK inhibitors have been identified. In this work, I aim to unravel the mechanism of NIK inhibition by different representative NIK type I 1/2 kinase inhibitors, using ADME, molecular docking, molecular dynamics simulation, MM-PBSA analysis and 3D-QSAR analysis. This work contributes to the understanding of the efficiency of NIK inhibitor binding by revealing the basis of the efficiency of NIK inhibitors, the difference in binding modes between different inhibitors and the overall effect on NIK.Communicated by Ramaswamy H. Sarma.

Discovery of lupus nephritis targeted inhibitors based on De novo molecular design: comprehensive application of vinardo scoring, ADMET analysis, and molecular dynamics simulation.

Lupus Nephritis (LN) is an autoimmune disease affecting the kidneys, and conventional drug studies have limitations due to its imprecise and complex pathogenesis. Therefore, the aim of this study was to design a novel Lupus Nephritis-targeted drug with good clinical due potential, high potency and selectivity by computer-assisted approach.NIK belongs to the serine/threonine protein kinase, which is gaining attention as a drug target for Lupus Nephritis. we used bioinformatics, homology modelling and sequence comparison analysis, small molecule ab initio design, ADMET analysis, molecular docking, molecular dynamics simulation, and MM/PBSA analysis to design and explore the selectivity and efficiency of a novel Lupus Nephritis-targeting drug, ClImYnib, and a classical NIK inhibitor, NIK SMI1. We used bioinformatics techniques to determine the correlation between lupus nephritis and the NF-κB signaling pathway. De novo drugs design was used to create a NIK-targeted inhibitor, ClImYnib, with lower toxicity, after which we used molecular dynamics to simulate NIK SMI1 against ClImYnib, and the simulation results showed that ClImYnib had better selectivity and efficiency. Our research delves into the molecular mechanism of protein ligands, and we have designed and validated an excellent NIK inhibitor using multiple computational simulation methods. More importantly, it provides an idea of target designing small molecules.Communicated by Ramaswamy H. Sarma.

Unveiling the Effectiveness of Agency Cost and Firms' Size as Moderators Between CSR Disclosure and Firms' Growth.

The excellence of corporate governance in companies lies in their ability to adopt the corporate social responsibility (CSR), which enhances their growth. This study examines the effect of agency cost, firm size, and CSR disclosure on the firms' growth. Specifically, the study analyzed the agency cost and firms' size as the moderators that influence the firms' performance asymmetrically. In its approach, the study compiled data of 300 Pakistani listed companies, which have a significant concern with CSR for the period 2010-2018. Using the 2SLS and GMM instrumental panel regressions, our empirical results show that the agency cost is detrimental to the firms' growth. In contrast, the firms' size boosts the firms' growth. Moreover, the growth of firms with leverage declines and the presence of independent directors improves the firms' growth.

The Coupling and Coordinated Development from Urban Land Using Benefits and Urbanization Level: Case Study from Fujian Province (China).

In recent years, urbanization has been developing rapidly. However, it is also accompanied by land management problems, such as low land use efficiency. In this research, we manage to explore the temporal and spatial evolution laws as well as characteristics of the coupling and coordinated development between urbanization and land use benefits. Through this, it is possible for us to provide policy recommendations for the sustainable development of the urbanization in Fujian Province. In this study, we take prefecture-level municipal districts and county-level cities in Fujian as the research subject. We construct an index system, based on data in 2002, 2005, 2010, 2015, and 2017, to evaluate the urban land use benefits and urbanization. Besides, we leverage the Gini coefficient weighting method to give weight to each index and calculate the value of its benefits. Moreover, it is the relative development degree and the coupling coordination degree model that we comprehensively leverage to study the spatiotemporal evolution law of the coupling coordination degree (CCD). The results show that: (1) Urban land use benefits and urbanization level are positively correlated with the regional administrative level and economic development status; (2) The CCD of urban land use benefits and urbanization level in various regions of Fujian is still low. However, the overall development direction is good; (3) From the perspective of spatial distribution, the CCD owns a "center-periphery" pattern that is based on the law of diminishing CCD power from three central cities of Fuzhou, Xiamen, and Sanming. Consequently, it requires governments to take action. Firstly, they should promote the intensive land use in the urbanization process. Meanwhile, they should also pay attention to ecological environment protection. Besides, it is recommendable to give full play to the radiating and leading effect of central cities on surrounding ones. Finally, they are required to provide appropriate policies and resource support to peripheral cities.

Can Sense of Opportunity Identification Efficacy Play a Mediating Role? Relationship Between Network Embeddedness and Social Entrepreneurial Intention of University Students.

Social entrepreneurship is an entrepreneurial activity centering on solving social problems and creating social values, which can effectively alleviate the problems of sustainable development such as an excessive gap between the rich and the poor, a lack of resources and so on, and can resolve the "triple failures" of government, the market and public welfare departments to a certain extent. As the subjective attitude of entrepreneurs, entrepreneurial intention can predict a representational incidence rate of entrepreneurial behavior. Therefore, aimed at university students, a special group of entrepreneurs, this paper constructs a theoretical framework of "network embeddedness - sense of opportunity identification efficacy - university students' social entrepreneurial intention" from the perspective of social cognitive theory through 466 pieces of valid survey data, and uses Stata 14 to construct a multiple linear regression model to explore the mechanism of action between the three. The results show that university students' sense of opportunity identification efficacy can significantly and positively stimulate their social entrepreneurial intention, and the network embeddedness (network scale and network intensity) of entrepreneurs is also significantly and positively correlated with their sense of opportunity identification efficacy; however, via the hierarchical regression model, it was found that the sense of opportunity identification efficacy can only partially mediate the relationship between network embeddedness and university students' social entrepreneurial intention, which is mainly manifested in the positive correlation between university students' social entrepreneurial intention and their network scale, and is unrelated to network intensity. This research contributes to enriching the theory of social entrepreneurial intention and guides the strengthening of university students' social entrepreneurial intention in reality.