Search Results (18,240)

Jacaranone derived from Senecio scandens, a traditional Chinese medicine used for centuries, has been documented to exhibit anti-inflammatory and antiproliferative properties in various tumor cell lines. However, the mechanism of action and relationship between inflammation and apoptosis induced by jacaranone remain inadequately elucidated. In this study, the targets of jacaranone and cancer were identified from various databases, while potential targets and pathways were predicted through the analysis of the protein–protein interactions (PPI) network and pathway enrichment. Through a comprehensive network pharmacology analysis and corroborating experimental findings, we revealed that jacaranone induces tumor cell death by fine-tuning the tumor necrosis factor receptor 1 (TNFR1) downstream signaling pathway. TNFR1 serves as a key node that assembles into complexes I and II, regulating pathways including the nuclear factor (NF)-κB signaling pathway and the cell apoptosis pathway, which play crucial roles in cellular life activities. Jacaranone successfully guides survival signaling pathways to apoptotic mechanisms by inhibiting the assembly of complex I and promoting the formation of complex II. In particular, the main action mechanism of jacaranone lies in inducing the degradation of the inhibitor of apoptosis protein (cIAP)-2. cIAP-2 serves as an E3 ubiquitin ligase that ubiquitinates receptor-interacting serine/threonine-protein kinase 1 (RIPK1), thereby hindering the formation of complex I and effectively reducing the phosphorylation of Inhibitor of κB kinase (IKK) β. When the deubiquitylation process of RIPK1 is triggered, it may promote the formation of complex II, which ultimately leads to cell apoptosis. This fully demonstrates the key role of jacaranone in regulating TNFR1 complexes, especially through the degradation of cIAP-2. Taken together, jacaranone hinders the assembly of TNFR1 complex I and promotes the formation of complex II to induce apoptosis of cancer cells. Our findings unveil a novel mechanism underlying jacaranone, while also presenting a fresh approach for the development of new pharmaceuticals. Full article

Better understanding the complex mechanisms underlying the variations in crop residue burning (CRB) intensity and patterns is crucial for evaluating control strategies and developing sustainable policies aimed at the efficient recycling of crop residues. However, the intricate interplay between the CRB practices, climate variability, and human activities poses a significant challenge in this endeavor. Here, we utilize the high spatiotemporal resolution of satellite observations to characterize and explore the dynamics of summer CRB in North China at multiple scales. Between 2003 and 2012, there was a significant intensification of summer CRB in North China, with the annual number of burning spots increasing by an average of 499 (95% confidence interval, 252–1426) spots/year. However, in 2013, China promulgated the stringent Air Pollution Prevention and Control Action Plan, which led to a rapid decrease in the intensity of summer CRB. Local farmers also adjusted their burning practices, shifting from concentrated and intense burning to a more dispersed and uniformly intense approach. Between 2003 and 2020, the onset of summer CRB shifted earlier in North China by 0.75 (0.5–1.1) days/year, which is attributed to the combined effects of climate change and anthropogenic controls. Specifically, the onset time is found to be significantly and negatively correlated with spring temperature anomalies and positively correlated with anomalies in the number of spring frost days. Climate change has led to a shortened crop growing season, resulting in an earlier start to summer CRB. Moreover, the enhanced anthropogenic controls on CRB expedited this process, making the trend of an earlier start time even more pronounced from 2013 to 2020. Contrary to the earlier onset of summer CRB, the termination of local wheat residue burning experienced a notable delay by 1.0 (0.8–1.4) days/year, transitioning from mid-June to early July. Full article

Despite significant progress in the field of clinical oncology in terms of diagnostic and treatment methods, the results of anticancer therapy are still not fully satisfactory, especially due to limited response and high toxicity. This has forced the need for further research to finding alternative ways to improve success rates in oncological treatment. A good solution to this problem in the context of rapidly obtaining an effective drug that works on multiple levels of cancer and is also safe is the global strategy of repurposing an existing drug. Research into other applications of an existing drug enables a precise assessment of its possible mechanisms of action and, consequently, the broadening of therapeutic indications. This strategy is also supported by the fact that most non-oncological drugs have pleiotropic effects, and most of the diseases for which they were originally intended are multifactorial, which in turn is a very desirable phenomenon due to the heterogeneous and multifaceted biology of cancer. In this review, we will mainly focus on the anticancer potential of H1 antihistamines, especially the new generation that were not originally intended for cancer therapy, to highlight the relevant signaling pathways and discuss the properties of these agents for their judicious use based on the characteristic features of cancer. Full article

Digital transformation has become a new driving force for corporate development, widely embraced by managers. However, in the actual digital transformation process, some companies’ performances are characterized by “more talk, less action”. To measure the phenomenon, this paper innovatively constructs the Digital Disclosure Anomaly (DDA) indicator using Chinese A-share listed companies’ data from 2013 to 2021 and examines the impact of DDA on corporate innovation efficiency by Saying is Believing theory. We find that DDAs show a long-term negative impact on corporate innovation efficiency. Our mechanism analysis suggests that DDAs reduce innovation efficiency through resource misallocation, which is driven by two mechanisms: the manager squandering effect and the inefficient investment effect. Our results suggest that DDAs are harmful for corporate innovation efficiency by the Saying is Believing (SIB) effect and corporate DDA behavior is detrimental to sustainability in digital economy development. Full article

Given the growing interest of the rubber industry in seeking alternatives that contribute to environmental sustainability, this work aims to present a study of the mechanical, thermal, and structural properties of natural rubber composites using tannin extracted from Acacia mearnsii as an antioxidant agent. Tannin is a natural and biodegradable product, rich in polyphenols and known for its antioxidant properties. The analyses assessed the effectiveness of incorporating tannins (0, 1, 1.5, and 2 parts per hundred rubber) into sulfur-crosslinked natural rubber composites using a binary accelerator system across three distinct vulcanization schemes: conventional, semi-efficient, and efficient. Initially, tannin characterization tests were conducted, revealing characteristic polyphenol bands of proanthocyanidin catechins, a high total phenolic content, and a substantial reduction in antioxidant activity. These findings highlight the significant antioxidant potential of tannins, particularly for industrial and biological applications. The analyses of the characteristics of natural rubber composites with tannin incorporation indicated that the type of vulcanization process directly affects the antioxidant action of the plant tannin, with the tannins being most effective in the efficient system due to the formation of monosulfidic and disulfidic bonds. Furthermore, the incorporation of tannin did not compromise the physical and chemical properties of the materials, highlighting it as a viable additive for the rubber industry. Full article

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, its precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine’s molecular actions. Ketamine primarily works by antagonizing NMDA receptors, reducing GABAergic inhibition, and increasing glutamate release. This enhanced glutamate activates AMPA receptors, triggering crucial downstream cascades, including BDNF-TrkB and mTOR pathways, promoting synaptic proliferation and regeneration. Moreover, neuroimaging studies have demonstrated alterations in brain networks involved in emotional regulation, including the Default Mode Network (DMN), Central Executive Network (CEN), and Salience Network (SN), which are frequently disrupted in depression. Despite the promising findings, the literature reveals significant inaccuracies and gaps in understanding the full scope of ketamine’s therapeutic potential. For instance, ketamine engages with opioid receptors, insinuating a permissive role of the opioid system in amplifying ketamine’s antidepressant effects, albeit ketamine does not operate as a direct opioid agonist. Further exploration is requisite to comprehensively ascertain its safety profile, long-term efficacy, and the impact of genetic determinants, such as BDNF polymorphisms, on treatment responsiveness. Full article

Bile acids (BAs), a category of amphiphilic metabolites synthesized by liver cells and released into the intestine via the bile duct, serve a vital role in the emulsification of ingested fats during the digestive process. Beyond their conventional emulsifying function, BAs, with their diverse structures, also act as significant hormones within the body. They are pivotal in facilitating nutrient absorption by interacting with the farnesoid X receptor (FXR), and they serve as key regulators of lipid and glucose metabolism, as well as immune system balance. Consequently, BAs contribute to the metabolism of glucose and lipids, enhance the digestion and absorption of lipids, and maintain the equilibrium of the bile pool. Their actions are instrumental in addressing obesity, managing cholestasis, and treating diabetes, and are involved in the onset and progression of cancer. This paper presents an updated systematic review of the pharmacological mechanisms by which BAs target the FXR, incorporating recent findings and discussing their signaling pathways in the context of novel research, including their distinct roles in various disease states and populations. The aim is to provide a theoretical foundation for the continued research and clinical application of BAs. Full article

This paper is devoted to the study of stationary trajectories of free particles. From a classical point of view, this appears to be an almost trivial problem: Free particles should follow straight lines as predicted by Newton’s first law, and straight lines are indeed the stationary trajectories of the standard action integrals in the classical theory. In the following, however, a general relativistic approach is studied, and in this situation it is much less evident what action integral should be used. As it turns out, using the traditional Einstein–Hilbert principle gives us stationary states very much in line with the classical theory. But it is suggested that a different action principle, and in fact one which is closer to quantum mechanics, gives stationary states with a much richer structure: Even if these states in a sense can represent particles which obey the first law, they are also inherently rotating. Although we may still be far from understanding how general relativity and quantum mechanics should be united, this may give an interesting clue to why rotation (or rather spin, which is a different but related concept) seems to be the natural state of motion for elementary particles. Full article

The human skin is a remarkable organ capable of extensive regeneration, especially after severe injuries such as burns and related wounds. The de-epidermized dermis (DED) model has become a valuable in vitro tool for skin regeneration studies, particularly for testing the mechanism of action and the efficacy of clinical cutaneous cell therapies. To further improve the quality and robustness of these applications, our study focused on optimizing and standardizing DED tissue preparation and storage, enhancing its effectiveness for clinical testing. Therefore, we optimized the air-liquid interfacial culture medium composition by simplifying the historical formulation without compromising keratinocyte (therapeutic cell model) viability or proliferation. Furthermore, we investigated the impacts of adding burn wound exudates in the model by focusing on cell behavior for enhanced translational significance. The results revealed notable differences in keratinocyte adhesion and proliferation between burn wound exudates collected at the early stages and late stages of acute patient treatment, providing new information on a possible therapeutic window to apply cell therapies on burn patients. Generally, this study reported a robust method for the preclinical in vitro assessment of keratinocyte-based cutaneous cell therapies using DED models. Overall, the study underscored the importance of using in vitro models with enhanced translational relevance to better predict the clinical effects of cutaneous cell therapies in burn patient populations. Full article

Cotton topping is a crucial aspect of cotton production, inhibiting apical dominance in cotton plants. Existing cotton topping machinery often results in over-topping. To address this challenge, the characteristics of manual topping operations were emulated by incorporating bionic principles to analyze the motions involved. Studying the artificial topping action and the trajectory of hand movements led to the design of a bionic topping manipulator and a trajectory-generating mechanism, serving as the core component of the cotton topping device. A flat-bottomed follower disc cam mechanism was used to facilitate the automatic opening and closing of the manipulator. The cam’s working area was divided, its contour curve selected, and the manipulator’s pulling spring’s action point and length determined. Subsequently, parametric equations for the motion trajectory of the bionic topping manipulator were established. Building on the topping mechanism’s working principle, a mechanical model was developed to analyze the swing of cotton plants. The model demonstrates that the displacement at the free end of the stalk was primarily influenced by its length. A lifter was then designed to reduce plant swing amplitude and orderly distribute its top position. The designed prototype of a single-row cotton bionic topping device was tested and verified through orthogonal tests, using operating speed, rotational speed, and topping depth as test factors. The topping rate and over-topping rate served as the indices for testing. The results indicated an average topping rate of 78.67% and an over-topping rate of 8%. This was achieved at a 0.3 m/s operating speed, a 40 r/min rotational speed, and a 110 mm topping depth. Cotton topping devices demonstrated greater effectiveness in minimizing damage to cotton plants, and future research should focus on enhancing topping rates even further. This study provides a theoretical foundation and test data to support the design of cotton topping machinery, guiding future mechanical improvements and agricultural practices. Full article

While lithium-ion batteries (LIBs) have pushed the progression of electric vehicles (EVs) as a viable commercial option, they introduce their own set of issues regarding sustainable development. This paper investigates how using end-of-life LIBs in stationary applications can bring us closer to meeting the sustainable development goals (SDGs) highlighted by the United Nations. We focus on how this practice can support three of these goals, namely Goal 7: Affordable and Clean Energy, Goal 12: Responsible Consumption and Production, and Goal 13: Climate Action. We present a literature review that details the aging mechanisms of LIBs, namely battery degradation, state of charge, state of health, depth of discharge, remaining useful life, and battery management systems. Then, we thoroughly examine the environmental and economic benefits of using second-life EV batteries in stationary applications and how they align with the SDGs. Our review of the literature summarizes the most relevant research in battery aging, giving a foundation for further research and allowing effective legislation to be written around EVs. Additionally, our examination of the benefits of using second-life batteries motivates initiatives for sustainable practices, helping both corporations and legislators orient their ideals towards the SDGs. Full article

Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal–midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS. Full article

Cardiovascular disease (CVD) remains a leading global health concern, with atherosclerosis being its principal cause. Standard CVD treatments primarily focus on mitigating cardiovascular (CV) risk factors through lifestyle changes and cholesterol-lowering therapies. As atherosclerosis is marked by chronic arterial inflammation, the innate and adaptive immune systems play vital roles in its progression, either exacerbating or alleviating disease development. This intricate interplay positions the immune system as a compelling therapeutic target. Consequently, immunomodulatory strategies have gained increasing attention, though none have yet reached widespread clinical adoption. Safety concerns, particularly the suppression of host immune defenses, remain a significant barrier to the clinical application of anti-inflammatory therapies. Recent decades have revealed the significant role of adaptive immune responses to plaque-associated autoantigens in atherogenesis, opening new perspectives for targeted immunological interventions. Preclinical models indicate that vaccines targeting specific atherosclerosis-related autoantigens can slow disease progression while preserving systemic immune function. In this context, numerous experimental studies have advanced the understanding of vaccine development by exploring diverse targeting pathways. Key strategies include passive immunization using naturally occurring immunoglobulin G (IgG) antibodies and active immunization targeting low-density lipoprotein cholesterol (LDL-C) and apolipoproteins, such as apolipoprotein B100 (ApoB100) and apolipoprotein CIII (ApoCIII). Other approaches involve vaccine formulations aimed at proteins that regulate lipoprotein metabolism, including proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesteryl ester transfer protein (CETP), and angiopoietin-like protein 3 (ANGPTL3). Furthermore, the literature highlights the potential for developing non-lipid-related vaccines, with key targets including heat shock proteins (HSPs), interleukins (ILs), angiotensin III (Ang III), and a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS-7). However, translating these promising findings into safe and effective clinical therapies presents substantial challenges. This review provides a critical evaluation of current anti-atherosclerotic vaccination strategies, examines their proposed mechanisms of action, and discusses key challenges that need to be overcome to enable clinical translation. Full article

Emerging social, economic, and environmental concerns bring operational challenges and the worldwide economy has seen magnifying pressure to incorporate environmental performance (EP) as a part of strategic decision. Studies in the field of environmental management and, particularly, in the areas of green practices, zero waste, and green innovation have suggested that, if executed properly, these organizations are able to promote EP. Under these conditions, organizations’ practices and mechanisms that ensure the enhancement of the EP of these business organizations have gained the wider attention of researchers and management. Focused on the environment and social responsibility, this study explores the complex relationships within sustainable green supply chain management (GSCM) and explores whether GSCM practices significantly impact both zero waste management and green innovation. The analysis also studies whether there are possible beneficial links between zero waste management, green innovation and environmental performance (EP). Additionally, through assessing the level to which these items come together in sustainable strategic actions, the paper shows the correlation among four important topics: GSCM practices, green innovation (GI), zero waste management, and EP. This study explores the relations between zero waste management and EP as well as green innovation and EP, examining whether these aspects of green practices have a positive relationship with effective waste management techniques in the presence of GSCM practices. The paper analyses interactions between GSCM practices and EP, and the mediation role of zero waste management and GI. Moreover, the moderating role of green knowledge sharing (GKS) also been tested. A total of 389 managers in the manufacturing sector completed the survey and the results were analyzed applying SPSS 25.0 and partial least squares structural equation modeling (PLS-SEM). The findings confirmed a significant association among GSCM practices, GI, zero waste management, GKS, and EP. Furthermore, findings also revealed that zero waste management GI has a positive intervention role between GSCM practices and EP. GSCM practices facilitate the promotion of EP by incorporating eco-design, green purchasing, new techniques for production or processes, and green marketing that ensures waste reduction and recycling practices. Full article

Microbiological communities have a significant impact on health and disease. Candida are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then Candida infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of Candida albicans-based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti-Candida potential. Two compounds, PUB14 and PUB17, displayed selective antifungal activity without negatively affecting beneficial microbiota, such as Lactobacillus sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of PUB14 and PUB17 against C. albicans, coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by Candida reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs. Full article