Search Results (6,295)

From the Red Shirt heartlands of the North and Northeast to the conservative South and the fragmented middle-class electorate of Bangkok, Thailand’s regional divisions reflect a deeply contested relationship with centralized power. How these divisions shape citizens’ relative trust in local versus central government remains an open empirical question. Drawing on three waves of the Asian Barometer Survey conducted between 2014 and 2022 (pooled N = 3600), this study examines whether territorial location produces differential trust in local relative to central government. The findings are mixed. Regional differences are observable in baseline models, but their explanatory power diminishes once individual-level evaluations of political institutions and economic conditions are taken into account. Rural residents exhibit a smaller trust gap, indicating a weaker relative preference for local over central government, consistent with central welfare transfers sustaining support for the central tier. At the contextual level, higher regional poverty rates are associated with a compression of the trust gap between levels of government. Once poverty is introduced, the overall temporal increase observed by 2022 is no longer statistically significant. Structural economic geography explains much of the aggregate shift. Regional dynamics, however, are not uniform. The Northeast diverges sharply in the final wave, and the pattern holds across model specifications. The shift points to accumulated political alienation rooted in repeated episodes of electoral disenfranchisement. The findings carry direct implications for decentralization policy and territorial development strategy. Where regional trust gaps are driven by fiscal constraints on local government and accumulated political alienation, administrative redesign alone cannot restore citizen confidence in sub-national governance. Full article

Photovoltaic desert control (PVDC), an innovative model integrating clean energy development and desertification control, faces complex coordination challenges among local governments, local communities, and photovoltaic enterprises. This study constructs a tripartite evolutionary game model to identify the conditions that drive PVDC toward coordinated governance. The model defines a three-dimensional strategy space: government regulatory intensity (Strong vs. Lax), community willingness to cooperate (Active Cooperation vs. Passive Resistance), and enterprise ecological integration (Active Ecological Integration vs. Passive Land Occupation). Replicator dynamic equations are derived to characterize nonlinear interactions, and the stability conditions of eight pure-strategy equilibrium points are identified through Jacobian matrix eigenvalue analysis. Numerical simulations are conducted using a baseline parameter set that satisfies the Evolutionary Stable Strategy conditions for the ideal equilibrium E8, namely Strong Regulation, Active Cooperation, and Active Ecological Integration. The results show that the system can converge to E8 when higher-level rewards cover government regulation, subsidy, and community-support costs; when community cooperation benefits exceed livelihood opportunity costs and compensation incentives from resistance; and when enterprises’ effective ecological integration costs are lower than the combined benefits of subsidies, avoided fines, and long-term returns. Sensitivity analysis further indicates that government subsidies, fines, community support, cooperation income, and enterprise long-term benefits are key drivers of system evolution, while excessive regulation costs, high opportunity costs, and high ecological integration costs may hinder coordination. Qualitative evidence from four PVDC-related cases in Xinjiang provides practical illustrations broadly consistent with the model mechanisms. This study offers a dynamic analytical framework for designing incentive-compatible governance mechanisms in PVDC and similar multi-stakeholder ecological restoration projects. Full article

DC–DC converters are ubiquitous in consumer, industrial, commercial, and medical applications. In such voltage-, power-, and area-constrained systems, guaranteeing accurate output voltage remains a key challenge. Investigation of the fundamental cause of steady-state output errors in DC–DC converters, however, is largely absent in the literature. This work identifies systemic voltage offset error as one of the key contributors to steady-state output inaccuracy in PWM and peak–valley-controlled switched-inductor voltage regulators. It uses an insightful reverse-feedback translation framework to quantify the systemic offset as a function of the duty cycle, input voltage, sawtooth amplitude, propagation delays, load conditions, error amplifiers, and comparator. Furthermore, with the derived offset expressions, the paper develops accurate and low-overhead design guidelines to remove systemic errors by aligning the regulator’s steady-state equilibrium with its operating conditions. With the proposed offset “centering” and “elimination” techniques, the systemic error (that accounts for up to 2.1% variation in the steady-state output) is reduced by over 70% when centered and to zero when eliminated at room temperature. Overall, this work provides an insightful and generalized quantification of systemic offsets and describes low-overhead strategies to restore steady-state accuracy in practical PWM, hysteretic and peak/valley-controlled voltage regulators. Full article

The colonic epithelial barrier is a multilayered defense system comprising the mucus layer, intestinal epithelial cells (IECs), and the underlying lamina propria. These components collectively maintain mucosal homeostasis and restrict microbial translocation. Disruption of this barrier is a hallmark of chronic intestinal inflammation particularly in IBDs, and is primarily driven by pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, and IL-6. TNF-α and IFN-γ synergistically induce epithelial cell apoptosis and tight junction disassembly through mechanisms involving TNFR2 upregulation, myosin light chain kinase (MLCK) activation, and adherens junction destabilization. IL-1β amplifies paracellular permeability via NF-κB-dependent MLCK induction and OCLN downregulation, while IL-6 promotes barrier leakiness by upregulating CLDN-2 and sustaining self-reinforcing inflammatory loops that maintain chronic inflammation and impede epithelial repair. This leads to persistent immune-cell infiltration, chronic tight junction remodeling, and failure of barrier replenishment. Consequently, leaky colon facilitates microbial and antigen translocation into the lamina propria, further activating immune cells and perpetuating pro-inflammatory signaling. This review synthesizes current evidence and studies on the cooperative and self-reinforcing roles of pro-inflammatory cytokines, providing insight into the mechanisms underlying chronic intestinal barrier dysfunction and highlighting the need for therapeutic strategies that simultaneously target multiple inflammatory axes to restore barrier integrity in inflammatory bowel disorders. Full article

Ocular surface inflammation is a major disruptor of corneal epithelial homeostasis and a key driver of limbal stem cell deficiency (LSCD). Limbal stem cells (LSCs), residing within the specialized limbal niche, maintain corneal transparency through continuous epithelial renewal and by preventing conjunctival encroachment onto the corneal surface. Chronic or severe inflammatory insults—stemming from systemic autoimmune disorders, ocular surface diseases, infections, trauma, or environmental stressors—can damage both LSCs and their microenvironment, ultimately leading to limbal insufficiency. This review synthesizes current insights into the mechanisms by which inflammation impairs LSC survival, including cytokine-mediated cytotoxicity, oxidative stress, immune cell infiltration, and disruption of essential signaling pathways such as Wnt, Notch, and BMP. The distinction between LSC depletion and LSC dysfunction is highlighted, as residual stem cells may persist even in clinically advanced disease and can regenerate the corneal surface once the inflammatory milieu is corrected. Clinical manifestations, staging systems, and diagnostic markers—including p63α, ABCG2, and additional emerging molecular indicators—are summarized to support accurate assessment of LSCD severity. Current therapeutic strategies, ranging from anti-inflammatory medical management to surgical approaches such as SLET, CLET, and allogeneic transplantation, are reviewed alongside evolving regenerative and cell-based therapies. By integrating mechanistic understanding with clinical implications, this review underscores the critical interplay between inflammation and limbal niche failure and emphasizes the importance of early recognition and targeted intervention to preserve or restore LSC function. Full article

Distributed economic dispatch in AC distribution systems relies heavily on communication networks and is therefore vulnerable to denial-of-service (DoS) attacks. To address this issue, this paper proposes a resilient event-triggered distributed economic dispatch control strategy. Two typical DoS attack scenarios, namely communication-link blocking and node isolation, are first modeled, and an event-triggered distributed economic dispatch controller is then developed to maintain incremental cost consensus and system power balance while reducing communication overhead. Based on Lyapunov stability theory and a linear matrix inequality approach, sufficient conditions for the asymptotic stability of the closed-loop system are derived, tolerable bounds on the frequency and duration of DoS attacks are established, and the absence of Zeno behavior is proved. Simulations on the IEEE 33-bus AC distribution system show that, under load disturbances, dispatch-command variations, and DoS attacks, the proposed strategy can maintain stable system operation, restore dispatch performance after attacks, and reduce communication overhead by 91.86% compared with a fixed-step periodic updating baseline. These results demonstrate the effectiveness and resilience of the proposed method for distributed economic dispatch in AC distribution systems under DoS attacks. Full article

Background/Objectives: A high-fat diet (HFD) not only induces metabolic disorders but also causes oxidative damage to the lung tissue, triggering inflammatory responses. However, the detailed mechanisms by which HFD induces pulmonary oxidative stress and inflammation, particularly involving NF-κB/PPAR-γ signaling and lung microbiota, remain poorly understood, and effective dietary intervention strategies are still lacking. This study investigated the effects of HFD on lung tissue injury in mice and systematically evaluated the protective effects and potential mechanisms of Torreya grandis seed oil (TGO) and Torreya grandis seed diester oil (TGO-DG). Methods: After 12 weeks of HFD feeding, HFD group mice exhibited a marked increase in body weight (90.36%) compared with the control group, whereas body weight gain was significantly attenuated in the TGO (57.95%) and TGO-DG (55.78%) groups. Results: Biochemical analyses revealed that the levels of malondialdehyde (MDA), nitric oxide (NO), and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were significantly elevated in the HFD group, indicating pronounced oxidative stress and inflammatory responses in lung tissue. These symptoms were significantly attenuated by TGO and TGO-DG, with TGO-DG showing a more marked effect. Western blot (WB) results showed that both TGO and TGO-DG suppressed IL-6 expression and altered the expression of proteins in the NF-κB and PPAR-γ signaling pathways, which may contribute to the alleviation of pulmonary inflammation. Lung microbiota analysis revealed that TGO was associated with an increased proportion of Lactobacillus species, which correlated with the restoration of pulmonary microbial homeostasis. Conclusions: Overall, these results suggest that TGO and TGO-DG effectively alleviate HFD-induced oxidative stress and inflammation in lung tissue through regulation of inflammatory signaling pathways and lung microbiota composition. Notably, TGO-DG exhibited superior protective effects, highlighting its potential as a lipid ingredient. Full article

Cyanidin-3-O-Glucoside (C3G) is the primary anthocyanin-active component in bilberry, exhibiting various pharmacological activities such as antioxidant, anti-inflammatory, and lipid metabolism-regulating effects. To address the clinical need for non-alcoholic fatty liver disease (NAFLD) prevention and treatment, this study aimed to investigate the ameliorative effects of C3G on NAFLD pathology and elucidate its molecular mechanisms of protection via the AMPK pathway. After a one-week acclimatization period, 20 six-week-old SPF mice were randomly divided into four groups: normal diet control (NCD), high-fat diet model (HFD), HFD + L-C3G (100 mg/kg/day), and HFD + H-C3G (200 mg/kg/day). Except for the NCD group, the remaining groups were fed a 60% high-fat diet for four weeks to establish an early-stage NAFLD model, with successful model construction verified by weight and liver weight gain. From the fifth week onward, C3G groups received daily administration for four consecutive weeks, while control groups were given an equal volume of distilled water. Liver function, lipid metabolism, oxidative stress, and inflammatory levels were assessed using ELISA, H&E staining, and other methods. The results showed that C3G restored liver function in NAFLD mice, improved lipid metabolism disorders, reduced oxidative stress and inflammatory responses, and alleviated liver pathological damage. Mechanistic studies revealed that C3G regulated the expression of mRNA and proteins related to the AMPK/SIRT1/NF-κB signaling pathway, activating the pathway by upregulating AMPK and its upstream regulators while inhibiting NF-κB-mediated inflammatory responses. This study confirmed that C3G can ameliorate high-fat diet-induced NAFLD lesions by activating the AMPK/SIRT1/NF-κB pathway, providing a potential intervention strategy for NAFLD prevention and treatment. Full article

In the context of increasing climate variability and carbon neutrality targets, understanding the relative roles of climate and human activities is essential for accurately assessing vegetation carbon sink dynamics. This study develops a climate-controlled attribution framework to disentangle human-induced effects from natural climatic variability in Guizhou Province, a representative karst region of Southwest China. Using multi-source remote sensing and climate data from 2004 to 2023, net ecosystem productivity (NEP) was estimated, and its spatiotemporal dynamics were analyzed. A two-step attribution approach was applied to isolate climate-driven variability and quantify the contribution of anthropogenic activities. Results indicate that mean NEP increased significantly from 273 gC·m⁻²·yr⁻¹ in 2004 to 369 gC·m⁻²·yr⁻¹ in 2023, with a provincial average of 318 gC·m⁻²·yr⁻¹. Human activities are estimated to contribute a dominant share (approximately 60–75%), although uncertainties remain due to methodological limitations. Spatial analysis reveals pronounced heterogeneity, with stronger human-induced enhancement in eastern regions and mixed restoration–disturbance effects in ecologically fragile western areas. These findings suggest that ecological restoration policies in fragile karst ecosystems can generate amplified carbon sink responses beyond background climatic effects. These findings provide insights into understanding climate–carbon cycle interactions and improving region-specific climate mitigation strategies. Full article

The tumor suppressor protein phosphatase 2A (PP2A) plays a crucial role in regulating oncogenic signaling. Its inactivation, specifically through inhibitory phosphorylation at Tyr307 mediated by SET and CIP2A, contributes to breast cancer (BC) progression. Modulation of these interactions represents a promising pharmacological strategy to restore PP2A function. We integrated computational approaches with experimental validation to analyse SET/CIP2A mechanisms and explore how PP2A reactivation suppresses tumor progression. Molecular docking and dynamics simulations showed that the SET inhibitor/FTY-720 forms stable hydrogen bond networks with SET, disrupting its interaction with PP2A. In contrast, CIP2A suppressor/erlotinib interacts with CIP2A through weaker hydrophobic and π-interactions. Protein–protein interaction analyses indicate reduced SET/CIP2A binding to PP2A upon treatment, supporting a structural basis for PP2A reactivation. Gene expression analyses revealed upregulation of PP2A, SET, CIP2A, and cytoskeletal markers in tumor and metastatic tissues. Studies on Triple Negative Breast Cancer (TNBC) cells showed that FTY-720 and erlotinib significantly reduce PP2A-Tyr307 phosphorylation, restoring its activity. Additionally, both compounds decreased c-Myc levels and inhibited Src/FAK/paxillin/PAK1 and ERK signaling, attenuating migratory and proliferative pathways. Our findings identify the SET/CIP2A–PP2A axis as a pharmacological target for the design of next-generation PP2A activators, highlighting the potential of inhibition as a therapeutic strategy to counteract TNBC progression. Full article

To maintain homeostatic conditions and optimal function during stressors, mitochondria initiate retrograde signaling. The mitochondrial integrated stress response (ISR) and unfolded protein response (UPR^mt) are critical quality control mechanisms activated during instances of mitochondrial perturbations. Restoration of mitochondrial homeostasis is orchestrated by three transcription factors, ATF4, CHOP, and ATF5, which upregulate protective genes to counteract stress. As the health and function of skeletal muscle are heavily dependent on a highly adaptive mitochondrial network, defining how mitochondrial health is maintained across various conditions is essential. Although several studies demonstrate the importance of these responses following instances of stress, the signaling mechanisms required to initiate such pathways remain poorly characterized in skeletal muscle. This review examines how the mitochondrial ISR/UPR^mt and related transcription factors respond to organellar stress by emphasizing the molecular events that occur during exercise, aging and muscle disuse. By consolidating the literature, this work aims to highlight the current understanding of mitochondrial stress response signaling within skeletal muscle and thus emphasize areas for future research and potential therapeutic strategies during divergent metabolic conditions. Full article

Osteoporosis and hyperglycemia are increasingly recognized as dual public health concerns in T1DM. However, the precise molecular mechanisms by which exercise ameliorates these conditions, particularly the contribution of mechanosensitive channels such as Piezo1, remain incompletely elucidated. To explore these mechanisms, T1DM mice were subjected to a 6-week treadmill training protocol (15 m/min, 20 min/day, 6 days/week) to evaluate the functions of exercise on diabetic osteoporosis and hyperglycemia. Exercise intervention markedly improved bone quality in T1DM mice, alleviating osteoporotic manifestations, as evidenced by enhanced mechanical strength, restored bone microarchitecture, and normalized histomorphology. Concurrently, exercise significantly reduced hyperglycemia. To clarify the role of Piezo1, mechanical stretch was applied to Piezo1-knockout MC3T3-E1 (Piezo1^−/−) cells in vitro, mimicking the mechanical stimulation induced by exercise. Consistent with the in vivo results, mechanical stimulation facilitated osteogenic differentiation and glucose metabolism through Piezo1-mediated mechanotransduction. Importantly, these beneficial effects were substantially abrogated in Piezo1^−/− cells, highlighting the central role of Piezo1. Collectively, these findings demonstrate that Piezo1-mediated mechanotransduction constitutes a critical factor by which exercise mitigates osteoporosis and hyperglycemia in T1DM mice. This study provides a framework for the development of new therapeutic strategies targeting Piezo1-mediated mechanotransduction for T1DM management. Full article

Background: Traumatic brain injury (TBI) remains a major cause of neurological morbidity and mortality. Mitochondria, being embedded as one of the key organelles disrupted after injury, play a central role in regulating neuronal metabolism, oxidative balance, and cell survival, hence the growing interest in their role after TBI. Methods: We present a narrative review of the literature on mitochondrial dysfunction after TBI to highlight the potential role in diagnosis, monitoring, prognostication and treatment strategies. Following SANRA guidelines we conducted a synthesis of 159 selected references published between 1997 and 2026, including 70 references published from 2020 onward. Results: Mitochondrial dysfunction underpins bioenergetic failure through the impairment of critical regulatory pathways, including oxidative phosphorylation, dysregulated reactive oxygen species production, and dysregulated calcium handling. These changes trigger downstream processes of oxidative damage, epigenetic and proteomic remodeling, and activation of regulated cell death pathways such as apoptosis, necroptosis, and ferroptosis in the context of an inflammatory milieu. As such, mitochondrial-derived molecules (such as mitochondrial DNA and microRNA) are emerging candidate biomarkers of TBI severity and prognosis. Additionally, therapeutic approaches under investigation include inhibition of the mitochondrial permeability transition pore, mitigation of mitochondrial oxidative stress using targeted antioxidants, restoration of NAD⁺-dependent metabolic pathways, and metabolic support through ketogenic interventions. Conclusions: Mitochondrial biology is advancing our understanding of TBI and offers a promising framework for improving its management. Full article

Large-scale excavation for pumped-storage hydropower stations (PSPSs) in mountainous areas substantially alters slope soils and accelerates ecological degradation, yet quantitative multi-indicator assessments for such projects remain limited. This study integrates field surveys, laboratory analyses, and multi-temporal remote-sensing data to evaluate the disturbance-induced evolution of soil properties at two representative PSPSs in China. Soil bulk density and porosity measurements revealed significant compaction on disturbed slope surfaces, particularly on soil-dominated slopes. Key nutrient indicators, including organic matter, alkali-hydrolysable nitrogen, available phosphorus, and available potassium, showed consistent declines relative to adjacent undisturbed habitats. A comprehensive ecological degradation indicator (EDI) was constructed using five vegetation and soil spectral indices (RVI, NDVI, SAVI, SBI, and SM) weighted through the analytic hierarchy process. Time-series EDI mapping (2019–2023) demonstrated a progressive increase in moderately to extremely degraded areas during intensive construction stages. The results highlight the strong spatial heterogeneity of disturbance effects and underscore the necessity of soil-focused restoration strategies. This integrated assessment framework provides a scientific basis for guiding near-natural restoration and long-term soil–vegetation management in PSPS infrastructure landscapes. Full article

GLP-1 receptor agonists and dual GLP-1/GIP agonists have significantly transformed the treatment of obesity, enabling clinically meaningful weight reduction and improvements in cardiometabolic parameters. However, clinical trial data indicate that cessation of therapy is associated with biologically driven weight regain and a partial loss of metabolic benefits. This phenomenon underscores the chronic nature of obesity and the limited durability of effects achieved through pharmacotherapy alone. Nevertheless, structured clinical frameworks describing how to maintain satiety and metabolic stability after GLP-1/GIP dose reduction or discontinuation remain limited. The aim of this narrative review is to discuss the mechanisms underlying weight regain following dose reduction or discontinuation of GLP-1/GIP pharmacotherapy and to present strategies supporting long-term metabolic stabilisation. Weight regain is driven in part by persistent metabolic adaptations, including a reduction in resting energy expenditure (adaptive thermogenesis), alterations in the hunger–satiety axis (increased ghrelin, reduced leptin signalling), and potentially incomplete restoration of adipose tissue and liver-related metabolic function, although direct evidence in this specific setting remains limited. Weight loss is often accompanied by a reduction in fat-free mass, which further lowers energy expenditure and increases susceptibility to a positive energy balance after treatment cessation. It remains unclear whether pharmacological suppression of appetite results in sustained normalisation of endogenous satiety regulation after treatment cessation, and its effects on gut microbiota function remain uncertain. In clinical practice, key priorities include preserving muscle mass (adequate protein intake, resistance training), maintaining dietary nutrient density, stabilising postprandial glycaemia, and ensuring sufficient intake of fermentable fibre to support short-chain fatty acid production and gut–brain signalling. GLP-1/GIP pharmacotherapy should be viewed as a component of an integrated model of obesity treatment. We propose that long-term weight stabilisation may require a transition from pharmacologically induced satiety to satiety supported by diet quality, preserved fat-free mass, and metabolic stability. Further research is needed to define optimal post-treatment strategies and to identify patients in whom therapy can be safely reduced or discontinued. This transition should be regarded as a conceptual framework and forward-looking hypothesis requiring validation in prospective studies. Full article