NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway.

Articular cartilage damage and chondrocyte apoptosis are among the distinguishing features of osteoarthritis. (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) is a transient receptor potential cation channel subfamily M member 7 (TRPM7) channel inhibitor and was initially considered a potent inhibitor of small-conductance Ca2+-activated K+ channels(SK1-3 or KCa2.1-2.3 channels). Since SK is one of the targets for atrial fibrillation therapy, several studies have been conducted using NS8593 and it has been shown to be effective in improving atrial fibrillation in rats, dogs and horses. Recently, inhibition of TRPM7 has been reported to alleviate articular cartilage destruction. However, the role and mechanism of NS8593 on articular chondrocyte damage is unknown. The purpose of this study was to investigate the effect and mechanism of NS8593 on sodium nitroprusside (SNP)-induced chondrocyte apoptosis in vitro. The results showed that SNP decreased cell viability and induced chondrocyte apoptosis. NS8593 dose-dependently inhibited the SNP-induced decrease in cell viability and reduced chondrocyte apoptosis. In addition, SNP stimulation significantly increased the phosphorylation level of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), and NS8593 treatment partially reversed the alteration of STING phosphorylation level. Treatment with the STING inhibitor H-151 inhibited SNP-induced chondrocyte apoptosis. These results suggest that NS8593 may inhibit SNP-induced chondrocyte apoptosis by suppressing the STING signaling pathway.

Functions of Peroxiredoxins and Their Roles in Autoimmune Diseases.

Significance: Oxidative stress is a common feature of autoimmune diseases. Low levels of reactive oxygen species (ROS) generation are important for various biological processes. Redox homeostasis can be disrupted when there is an imbalance between the production of ROS and the detoxification effect of antioxidants. Peroxiredoxins (PRDXs) are essential regulators of cellular redox signaling. Recent Advances: PRDXs are widely expressed antioxidant enzymes, and their physiological role is mainly to remove excess ROS in cells and reduce oxidative stress. Recent studies have shown that almost all PRDX subtypes are involved in the development of autoimmune diseases. Critical Issues: The pathogenesis of autoimmune diseases is complex, and effective treatments are lacking. Therefore, there is an urgent need to find new therapeutic targets. In this review, we discuss the functions of PRDXs and their pathophysiological roles in several autoimmune diseases. PRDXs may serve as potential targets for the treatment of autoimmune diseases. Future Directions: PRDXs are important in oxidative stress-mediated pathological situations. Future in-depth exploration of the mechanisms involved in regulating PRDXs in autoimmune diseases is needed to develop strategies targeting PRDXs for the treatment of autoimmune diseases. Antioxid. Redox Signal. 40, 329-344.

Targeting regulated chondrocyte death in osteoarthritis therapy.

In vivo articular cartilage degeneration is an essential hallmark of osteoarthritis (OA), involving chondrocyte senescence, extracellular matrix degradation, chondrocyte death, cartilage loss, and bone erosion. Among them, chondrocyte death is one of the major factors leading to cartilage degeneration. Many studies have reported that various cell death modes, including apoptosis, ferroptosis, and autophagy, play a key role in OA chondrocyte death. Currently, there is insufficient understanding of OA pathogenesis, and there remains a lack of treatment methods to prevent OA and inhibit its progression. Studies suggest that OA prevention and treatment are mainly directed to arrest premature or excessive chondrocyte death. In this review, we a) discuss the forms of death of chondrocytes and the associations between them, b) summarize the critical factors in chondrocyte death, c) discuss the vital role of chondrocyte death in OA, d) and, explore new approaches for targeting the regulation of chondrocyte death in OA treatment.

A theoretical model of factors influencing online consumer purchasing behavior through electronic word of mouth data mining and analysis.

The coronavirus disease 2019 pandemic has impacted and changed consumer behavior because of a prolonged quarantine and lockdown. This study proposed a theoretical framework to explore and define the influencing factors of online consumer purchasing behavior (OCPB) based on electronic word-of-mouth (e-WOM) data mining and analysis. Data pertaining to e-WOM were crawled from smartphone product reviews from the two most popular online shopping platforms in China, Jingdong.com and Taobao.com. Data processing aimed to filter noise and translate unstructured data from complex text reviews into structured data. The machine learning based K-means clustering method was utilized to cluster the influencing factors of OCPB. Comparing the clustering results and Kotler's five products level, the influencing factors of OCPB were clustered around four categories: perceived emergency context, product, innovation, and function attributes. This study contributes to OCPB research by data mining and analysis that can adequately identify the influencing factors based on e-WOM. The definition and explanation of these categories may have important implications for both OCPB and e-commerce.

Understanding the Green Procurement Behavior of Household Appliance Manufacturing Industry: An Empirical Study of the Enablers.

Green procurement, as a crucial green supply chain practice, contributes to sustainability achievement and reduces carbon emissions by selecting sustainable suppliers or outsourcing partners. The green procurement of household appliance manufacturing can reduce carbon emissions from the source and increase the competitiveness of products. To help better understand the driving powers and influential mechanism of green purchasing behavior for household appliance manufacturers, the green procurement mechanism is investigated by presenting an empirical study considering both endogenous and exogenous factors. A survey-based questionnaire is designed, and a semistructured interview is conducted for data collection. Besides, the structural equation model (SEM) approach is employed to test the supposed hypotheses and proposed assumptions based on the collected 529 questionnaire responses. The empirical results show that exogenous driving powers are more inclined to encourage household appliance manufacturers to perform green procurement strategy compared with endogenous factors. Additionally, the business strategy, governmental regulations, and customer awareness show greater influence on green purchasing behavior, while the corporate culture, production system, and suppliers have little impact. Taxation policies, environmental awareness, and green strategies are the three main driving factors for promoting green procurement from the governmental, individual, and organizational dimensions. This empirical study assists to investigate potential factors affecting green purchasing behavior and helps to disclose the influential mechanisms from a systematic viewpoint. Results derived from the empirical analysis could assist to achieve sustainability by better understanding green purchasing behavior and better promoting green procurement strategies.

L-Proline, a resolution agent able to target both enantiomers of mandelic acid: an exciting case of stoichiometry controlled chiral resolution.

We present a thought-provoking development in chiral resolution. Using a resolving agent of a given handedness, L-proline, we show that both R- and S-enantiomers of mandelic acid can be resolved from a racemic mixture simply by varying the stoichiometry. We are the first to report this specific feature, achieved by the existence of stoichiometrically diverse cocrystal systems between R- and S-mandelic acid and L-proline.

New Quality Cost Framework (QCF) Based on the Hybrid Fuzzy MCDM Approach.

Quality cost framework (QCF), as a measurement tool and research method, has played a significant role on quality improvement procedure (QIP) and recognition on economics of quality. The four general QCFs are usually conceptually employed assist quality managers to measure the quality cost (QC/COQ) including PAF, intangible loss, process cost, and ABC framework. The question of how to select an appropriate quality cost framework for individual organization is of great significance for implementing quality improvement activities. Considering the effectiveness and feasibility of the alternative solution, a novel hybrid fuzzy MCDM approach integrating fuzzy DMEATEL, an antientropy weighting technique and FVIKOR method are employed to study the quality cost models and assist managers to select a best QCF for an auto factory. The combined weight from subjectivity and objectivity is embedded into fuzzy VIKOR procedure to obtain alternatives' ranking order. The case study in a Chinese automaker enterprise shows high robustness of the hybrid MCDM approach, and it assists quality mangers to perform quality cost practice. Different from the previous study, the preferred solution is the ABC quality cost framework when feasibility dimension dominates, while the intangible loss framework shows first priority when the organization focuses on effectiveness principle.

Simultaneous Chiral Resolution of Two Racemic Compounds by Preferential Cocrystallization*.

We tap into an unexplored area of preferential crystallization, being the first to develop simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. We highlight how the two racemic compounds RS-mandelic acid (MAN) and RS-etiracetam (ETI) can be combined together as enantiospecific R-MAN⋅R-ETI and S-MAN⋅S-ETI cocrystals forming a stable conglomerate system and subsequently develop a cyclic preferential crystallization allowing to simultaneous resolve both compounds. The developed process leads to excellent enantiopurity both for etiracetam (ee>98 %) and mandelic acid (ee≈95 %) enantiomers.