Search Results (5,768)

China has identified the high-quality development of its green manufacturing transition as the top priority for upgrading their industrial structure system which will lead to the sustainable development of an innovation ecosystem. To assess their progress in this area, this study selects the panel data of 31 provinces in China from 2011 to 2021 and constructs an evaluation index system for the green transformation of the manufacturing industry from four dimensions: environment, resources, economy, and industrial structure. This not only comprehensively and systematically reflects the dynamic changes in the green transformation of the manufacturing industry but also addresses the limitations of currently used indices. The entropy value method is used to calculate the comprehensive score of the green transformation of the manufacturing industry, while the key factors influencing the convergence of the green transformation of the manufacturing industry are further explored. The results show that first, the overall level of the green transformation of the manufacturing industry has significantly improved as evidenced by an approximate 32% increase. Second, regional differences are significant with the eastern region experiencing significantly higher levels of transformation compared to the central and western regions, along with a decreasing trend from the east to the central and western regions. From a policy perspective, the findings suggest that tailored production methods for each region should be adopted with a greater emphasis on knowledge exchanges to promote green transition in less developed regions. In addition, further regulations are required which, in part, focus on increasing the degree of openness to the outside world to promote the level of green manufacturing transition. Full article

In river-connected lake regions, both land use and hydrological regime changes may affect the ecosystem services; however, few studies have attempted to elucidate their complex influences. In this study, the spatiotemporal dynamics of eight ecosystem services (crop production, aquatic production, water yield, soil retention, flood regulation, water purification, net primary productivity, and habitat quality) were investigated through remote-sensing images and the InVEST model in the Dongting Lake Region during 2000–2020. Results revealed that crop and aquatic production increased significantly from 2000 to 2020, particularly in the northwestern and central regions, while soil retention and net primary productivity also improved. However, flood regulation, water purification, and habitat quality decreased, with the fastest decline in habitat quality occurring at the periphery of the Dongting Lake. Land-use types accounted for 63.3%, 53.8%, and 40.3% of spatial heterogeneity in habitat quality, flood regulation, and water purification, respectively. Land-use changes, particularly the expansion of construction land and the conversion of water bodies to cropland, led to a sharp decline in soil retention, flood regulation, water purification, net primary productivity, and habitat quality. In addition, crop production and aquatic production were higher in cultivated land and residential land, while the accompanying degradation of flood regulation, water purification, and habitat quality formed a “production-pollution-degradation” spatial coupling pattern. Furthermore, hydrological fluctuations further complicated these dynamics; wet years amplified agricultural outputs but intensified ecological degradation through spatial spillover effects. These findings underscore the need for integrated land-use and hydrological management strategies that balance human livelihoods with ecosystem resilience. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

Tauopathies are a diverse group of neurodegenerative diseases characterized by the presence of Tau inclusions in neurons and glia. Rather than the classic steps in the transformation of Tau into neurofibrillary tangles, as first studied in Alzheimer’s disease, studies on tauopathies reveal the presence of diverse Tau aggregates that appear to be disease-specific. Regardless, the phosphorylation and hyperphosphorylation of Tau, involving various kinases and phosphatases, appear to be central to all tauopathies. As in other neurodegenerative diseases, calcium dysregulation is an early event in multiple tauopathies, where it activates calmodulin to effect downstream events. Here, the events of Tau phosphorylation and hyperphosphorylation, which involve several CaM-dependent kinases and a single CaM-regulated phosphatase, are covered. In addition, CaM has been linked to other events, including Tau aggregation. As a central player in tauopathies, CaM offers several alternative therapeutic routes that are worth investigating. For example, evidence is presented here that supports targeting specific binding motifs of key CaM-regulated Tau kinases as a novel therapeutic approach. Full article

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation participating in various diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular redox homeostasis and a key determinant of ferroptosis resistance. Nrf2 activates the expression of downstream antioxidant genes to protect cells from oxidative stress and ferroptosis. Consequently, precise regulation of Nrf2 expression is crucial. Recent studies have revealed that complex epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA networks regulate Nrf2 expression. DNA methylation usually suppresses while histone acetylation promotes Nrf2 expression. The influences of histone methylation on NFE2L2 are site- and methylation degree-dependent. m6A modification stabilizes NFE2L2 mRNA to promote Nrf2 expression and thereby inhibit ferroptosis. This article summarizes current understanding of the epigenetic mechanisms controlling Nrf2 expression and Nrf2-mediated ferroptosis pathways and their implications in disease models. The challenges associated with the epigenetic regulation of Nrf2 and future research directions are also discussed. A comprehensive understanding of this regulatory interplay could open new avenues for intervention in ferroptosis-related diseases by fine-tuning cellular redox balance through the epigenetic modulation of Nrf2. Full article

The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Insulin-regulated glucose uptake is a central mechanism in maintaining systemic glucose homeostasis, primarily occurring in skeletal muscle and adipose tissue. This process relies on the insulin-stimulated translocation of the glucose transporter, GLUT4, from specialized intracellular compartments, known as GLUT4 storage vesicles (GSVs), to the plasma membrane. Disruption of this pathway is a hallmark of insulin resistance and a key contributor to the pathogenesis of type 2 diabetes. Recent advances have provided critical insights into both the insulin signalling cascades and the complex biogenesis, as well as the trafficking and fusion dynamics of GSVs. This review synthesizes the current understanding of the molecular mechanisms governing GSV mobilization and membrane fusion, highlighting key regulatory nodes that may become dysfunctional in metabolic disease. By elucidating these pathways, we propose new therapeutic avenues targeting GSV trafficking to improve insulin sensitivity and combat type 2 diabetes. Full article

The green renovation of existing residential buildings is a key way for the construction industry to achieve sustainable development and the dual carbon goals of China, which makes it urgent to make collaborative decisions among multiple stakeholders. However, because of divergent interests and risk perceptions among governments, energy service companies (ESCOs), and owners, the implementation of green renovation is hindered by numerous obstacles. In this study, we integrated prospect theory and evolutionary game theory by incorporating core prospect-theory parameters such as loss aversion and perceived value sensitivity, and developed a psychologically informed tripartite evolutionary game model. The objective was to provide a theoretical foundation and analytical framework for collaborative governance among stakeholders. Numerical simulations were conducted to validate the model’s effectiveness and explore how government regulation intensity, subsidy policies, market competition, and individual psychological factors influence the system’s evolutionary dynamics. The findings indicate that (1) government regulation and subsidy policies play central guiding roles in the early stages of green renovation, but the effectiveness has clear limitations; (2) ESCOs are most sensitive to policy incentives and market competition, and moderately increasing their risk costs can effectively deter opportunistic behavior associated with low-quality renovation; (3) owners’ willingness to participate is primarily influenced by expected returns and perceived renovation risks, while economic incentives alone have limited impact; and (4) the evolutionary outcomes are highly sensitive to parameters from prospect theory, The system’s evolutionary outcomes are highly sensitive to prospect theory parameters. High levels of loss aversion (λ) and loss sensitivity (β) tend to drive the system into a suboptimal equilibrium characterized by insufficient demand, while high gain sensitivity (α) serves as a key driving force for the system’s evolution toward the ideal equilibrium. This study offers theoretical support for optimizing green renovation policies for existing residential buildings in China and provides practical recommendations for improving market competition mechanisms, thereby promoting the healthy development of the green renovation market. Full article

Microglia, the brain’s resident innate immune cells, play a fundamental role in maintaining neural homeostasis and mediating responses to injury or infection. Upon activation, microglia undergo morphological and functional changes, including phenotypic switching between pro- and anti-inflammatory types and the release of different inflammatory mediators. These processes contribute to neuroprotection and the pathogenesis of various central nervous system (CNS) disorders. Mast cells, although sparsely located in the brain, exert a significant influence on neuroinflammation through their interactions with microglia. Through degranulation and secretion of different mediators, mast cells disrupt the blood–brain barrier and modulate microglial responses, including alteration of microglial phenotypes. Notably, mast cell-derived factors, such as histamine, interleukins, and tryptase, activate microglia through various pathways including protease-activated receptor 2 and purinergic receptors. These interactions amplify inflammatory cascades via various signaling pathways. Previous studies have revealed an exceedingly complex crosstalk between mast cells and microglia suggesting a bidirectional regulation of CNS immunity, implicating their cooperation in both neurodegenerative progression and repair mechanisms. Here, we review some of the diverse communication pathways involved in this complex interplay. Understanding this crosstalk may offer novel insights into the cellular dynamics of neuroinflammation and highlight potential therapeutic targets for a variety of CNS disorders. Full article

Heat stress in dairy cows, caused by high temperature and humidity during summer, has led to significant declines in milk production and severe economic losses for farms. Exosomes—extracellular vesicles carrying bioactive molecules—are critical for intercellular communication and immunity but remain understudied in heat-stressed Holstein cows. In this study, we extracted exosomes from three heat-stressed (HS) cows and three non-heat-stressed (Ctr) cows and employed proteomics to analyze plasma exosomes. We identified a total of 28 upregulated and 18 downregulated proteins in the HS group compared to the control group. Notably, we observed a significant upregulation of key protein groups, including cytoskeletal regulators, signaling mediators, and coagulation factors, alongside the downregulation of HP-25_1. These differentially expressed proteins demonstrate strong potential as heat stress biomarkers. GO and KEGG analyses linked the differentially expressed proteins to actin cytoskeleton regulation and endoplasmic reticulum pathways. Additionally, protein–protein interaction (PPI) analysis revealed the PI3K-Akt signaling pathway as a central node in the cellular response to heat stress. These findings establish plasma exosomes as valuable biospecimens, provide valuable insights into the molecular mechanisms of heat stress response, and may contribute to the development of precision breeding strategies for enhanced thermal resilience in dairy herds. Full article

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies. Full article

With the rapid pace of urbanization, cities are increasingly facing severe challenges related to environmental pollution, ecological degradation, and climate change. Extreme climate events—such as heatwaves, droughts, heavy rainfall, and wildfires—have intensified public concern about sustainability, environmental protection, and low-carbon development. Ensuring environmental preservation while maintaining residents’ quality of life has become a central focus of urban governance. In this context, evaluating green indicators and predicting urban greenness is both necessary and urgent. This study incorporates international frameworks such as the EU Green City Index, the European Green Capital Award, and the United Nations Sustainable Development Goals to assess urban sustainability. The Extreme Gradient Boosting (XGBoost) algorithm is employed to predict the green level of cities and to develop multiple optimized models. Comparative analysis with traditional models demonstrates that XGBoost achieves superior performance, with an accuracy of 0.84 and an F1-score of 0.81. Case study findings identify “Greenhouse Gas Emissions per Person” and “Per Capita Emissions from Transport” as the most critical indicators. These results provide practical guidance for policymakers, suggesting that targeted regulations based on these key factors can effectively support emission reduction and urban sustainability goals. Full article

Population aging poses significant challenges to the sustainability of pension systems. This study presents an integrated methodological approach that uniquely combines actuarial life-cycle modeling with agent-based simulation to assess the potential of Reverse Mortgage Loans (RMLs) as a dual lever for enhancing retiree welfare and supporting pension system resilience under demographic and financial uncertainty. We explore Reverse Mortgage Loans (RMLs) as a potential financial instrument to support retirees while alleviating pressure on public pensions. Unlike prior research that treats individual decisions or policy outcomes in isolation, our hybrid model explicitly captures feedback loops between household-level behavior and system-wide financial stability. To test our hypothesis that RMLs can improve individual consumption outcomes and bolster systemic solvency, we develop a hybrid model combining actuarial techniques and agent-based simulations, incorporating stochastic housing prices, longevity risk, regulatory capital requirements, and demographic shifts. This dual-framework enables a structured investigation of how micro-level financial decisions propagate through market dynamics, influencing solvency, pricing, and adoption trends. Our central hypothesis is that reverse mortgages, when actuarially calibrated and macroprudentially regulated, enhance individual financial well-being while preserving long-run solvency at the system level. Simulation results indicate that RMLs can improve consumption smoothing, raise expected utility for retirees, and contribute to long-term fiscal sustainability. Moreover, we introduce a dynamic regulatory mechanism that adjusts capital buffers based on evolving market and demographic conditions, enhancing system resilience. Our simulation design supports multi-scenario testing of financial robustness and policy outcomes, providing a transparent tool for stress-testing RML adoption at scale. These findings suggest that, when well-regulated, RMLs can serve as a viable supplement to traditional retirement financing. Rather than offering prescriptive guidance, this framework provides insights to policymakers, financial institutions, and regulators seeking to integrate RMLs into broader pension strategies. Full article

CNOT2, a central component of the CCR4-NOT transcription complex subunit 2, plays a pivotal role in the regulation of gene expression and metabolism. CNOT2 is involved in various cellular processes, including transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability. CNOT2 specifically contributes to the structural integrity and enzymatic activity of the CCR4-NOT complex with transcription factors and RNA-binding proteins. Recent studies have elucidated its involvement in cellular differentiation, immune response modulation, and the maintenance of genomic stability. Abnormal regulation of CNOT2 has been implicated in a spectrum of pathological conditions, including oncogenesis, neurodegenerative disorders, and metabolic dysfunctions. This review comprehensively examines the interplay between CNOT2 and p53, elucidating their collaborative and antagonistic interactions in various cellular contexts. CNOT2 is primarily involved in transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability, thereby influencing diverse biological processes such as cell proliferation, apoptosis, and differentiation. Conversely, p53 is renowned for its role in maintaining genomic integrity, inducing cell cycle arrest, apoptosis, and senescence in response to cellular stress and DNA damage. Emerging evidence suggests that CNOT2 can modulate p53 activity through multiple mechanisms, including the regulation of p53 mRNA stability and the modulation of p53 target gene expression. The dysregulation of CNOT2 and p53 interactions has been implicated in the pathogenesis and progression of various cancers, highlighting their potential as therapeutic targets. Additionally, CNOT2 regulates c-Myc, a well-known oncogene, in cancer cells. This review shows the essential roles of CNOT2 in maintaining cancer cellular homeostasis and explores its interactions within the CCR4-NOT complex that influence transcriptional and post-transcriptional regulation. Furthermore, we investigate the potential of CNOT2 as a biomarker and therapeutic target across various disease states, highlighting its significance in disease progression and treatment responsiveness. Full article