Search Results (21,514)

Background: Gut microbiota dysregulation is increasingly recognized as a key contributor to the progression of liver cirrhosis and its complications, particularly hepatic encephalopathy. Fecal microbiota transplantation (FMT) has emerged as a novel therapeutic strategy aimed at restoring intestinal microbial homeostasis and modulating systemic inflammation. Methods: This prospective, single-center clinical trial evaluated the short-term safety and efficacy of FMT in patients with alcohol-related liver cirrhosis. Clinical assessment, liver stiffness (via elastography), steatosis (controlled attenuation parameter), inflammatory biomarkers, and extended biochemical panels were analyzed at baseline, one week and one month post-FMT. A control group receiving standard medical therapy was used for comparison. Results: FMT was associated with a significant reduction in hepatic encephalopathy severity (p = 0.014), sustained improvements in liver stiffness (p = 0.027) and decreased steatosis (p = 0.025). At one month, C-reactive protein and neutrophil-to-lymphocyte ratio both declined significantly (p = 0.043), indicating a measurable anti-inflammatory effect. No serious adverse events were recorded. In comparison with controls, FMT recipients showed lower systemic inflammation and improved neuropsychiatric status. Conclusions: FMT demonstrated a favorable safety profile and yielded early clinical and biochemical benefits in patients with cirrhosis. These preliminary findings support the potential utility of microbiota-based interventions in chronic liver disease and warrant validation in larger, multicenter trials. Full article

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, and key pathways such as neuroinflammation, oxidative stress, and autophagy are believed to significantly contribute to the mechanisms of neurodegeneration. Calpain activation plays a critical role in neuroinflammation and neurodegeneration, as demonstrated by its impact on microglial activation, reactive oxygen species (ROS) production, and neuronal survival. In this study, we investigated the effects of calpain inhibition using calpeptin (CP) and calpain-2-specific inhibitors in cellular and murine models of neuroinflammation and PD. In BV2 microglial cells, LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-6) and chemokines (MCP-1, IP-10) were significantly reduced by CP treatment with a concomitant decrease in ROS generation. Similarly, in VSC-4.1 motoneuron cells, calpain inhibition attenuated IFN-γ-induced ROS production and improved cell viability, demonstrating its neuroprotective effects. Moreover, in a murine MPTP model of PD, calpain inhibition reduced astrogliosis, ROCK2 expression, and levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-7, and IL12p70) and chemokines (MCP-1 and IP-10) in the dorsal striatum and plasma. The specific role of calpain-2 in immune modulation was further highlighted in human microglia, SV-40 cells. With respect to immune modulation in these cells, siRNA-mediated knockdown of calpain-2, but not calpain-1, significantly reduced antigen presentation to CD4+ T cells. Thus, calpain-2 is likely involved in regulating antigen presentation and activation of inflammatory CD4+ T cells. These findings underscore the therapeutic potential of calpain-2 inhibition in mitigating neuroinflammation and neurodegeneration, particularly in PD, by targeting microglial activation, ROS production, and neuronal survival pathways. Full article

Background: Physical inactivity is a major contributor to increased mortality among aging populations, especially in middle-aged and older adults. Methods: Data were derived from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020). Participants self-reported their physical activity frequency, categorized as low (≤1 day/week), medium (2–4 days/week), or high (≥5 days/week). All-cause mortality was tracked through verified records. Cox proportional hazards models were used to estimate hazard ratios (HRs), with adjustments for demographics, lifestyle factors, and baseline health conditions. Results: A total of 2092 participants (mean age = 63.7 ± 10.4 years) were included in the final analytic sample. Higher physical activity frequency was significantly associated with lower mortality in unadjusted models. Participants engaging in activity ≥5 days/week had a 67% reduced mortality risk compared to the low-frequency group (HR = 0.33, p < 0.001). However, after adjusting for health-related covariates, the protective effect was attenuated and no longer statistically significant. In the fully adjusted model, advanced age, current smoking, and ADL limitations emerged as the strongest independent risk factors for mortality, while being married and residing in a rural area were significantly protective effects. Conclusions: The association between frequent physical activity and reduced mortality risk among Chinese older adults is profoundly mediated by baseline health status and functional capacity. These findings highlight the importance of integrated, multifactorial public health interventions that address chronic disease management and functional rehabilitation alongside physical activity promotion. Full article

Heart failure (HF) remains a major global health challenge defined by the inability of the heart to adequately meet systemic metabolic requirements. While ventricular dysfunction has traditionally been the primary focus in both conceptual and clinical frameworks of HF, emerging evidence highlights atrial myopathy—covering structural, functional, electrical, metabolic, and neurohormonal remodeling—as a central yet often overlooked contributor to disease progression across the HF spectrum. This review offers a comprehensive overview of the molecular and cellular mechanisms underlying atrial remodeling, with a focus on inflammation and innate immune activation as key pathogenic mediators. Among pattern recognition receptors, Toll-like receptors (TLRs) and NOD-like receptors (NLRs) play crucial roles in translating myocardial stress into pro-inflammatory, profibrotic, and pro-arrhythmic signals that exacerbate HF. By combining experimental and clinical evidence, we emphasize atrial myopathy as both a biomarker and an active driver of HF deterioration, advocating for the inclusion of atrial-targeted diagnostics and immunomodulatory therapies in future HF treatment approaches. Such a paradigm shift holds significant potential for improved risk stratification, arrhythmia prevention, attenuation of structural remodeling, and ultimately, better prognosis and clinical outcomes in this increasingly common syndrome. Full article

Background/Objetives: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Nutritional disorders, particularly cachexia, significantly impact morbidity and mortality in IPF but remain under-investigated. This study aimed to characterize cachexia phenotypes in IPF through morphofunctional assessment (MFA) and to evaluate their prognostic relevance, including the role of mitochondrial biomarkers. Methods: In this prospective bicenter study, 85 IPF patients underwent MFA including bioelectrical impedance vector analysis (BIVA), nutritional ultrasound (NU), and T12-level computed tomography (T12-CT) for body composition. Functional and strength assessments included timed up and go test (TUG) and handgrip strength (HGS), respectively. Cachexia was defined by Evans’ criteria, Martin’s CT-based criteria, and our IPF-specific proposed definition. Serum GDF-15 and PGC-1α levels were also measured. Results: Cachexia prevalence varied by definition: 24.71% (Evans), 29.5% (Martin) and 42.4% (IPF Cachexia Syndrome). Cachectic patients showed significantly lower muscle mass, function, and quality (measured by reduced muscle attenuation at T12-CT), along with higher GDF-15 and lower PGC-1α levels. The presence of IPF Cachexia syndrome (HR 2.56; 95% CI, 1.08–6.07; p = 0.033), GDF-15 > 4412.0 pg/mL (HR 3.21; 95% CI, 1.04–9.90; p = 0.042) and impaired TUG (>8 s) (HR 3.77; 95% CI, 1.63–8.71; 0.002) were all independently associated with increased 24-month mortality. Conclusions: Cachexia is prevalent in IPF and showed strong concordance between the three diagnostic criteria. The IPF Cachexia syndrome, based on comprehensive morphofunctional phenotyping, demonstrated superior discriminatory capacity. The addition of mitochondrial biomarkers may improve early detection and support personalized interventions to improve patient outcomes. Full article

Utilizing a coupled Computational Fluid Dynamics and Discrete Element Method (CFD-DEM) approach, this study constructs a comprehensive three-dimensional numerical model to simulate particle migration dynamics within rough artificial fractures subjected to the high-energy impact of water inrush. The model explicitly incorporates key governing factors, including intricate fracture wall geometry characterized by the joint roughness coefficient (JRC) and aperture variation, hydraulic pressure gradients representative of inrush events, and polydisperse sand particle sizes. Sophisticated simulations track the complete mobilization, subsequent acceleration, and sustained transport of sand particles driven by the powerful high-pressure flow. The results demonstrate that particle migration trajectories undergo a distinct three-phase kinetic evolution: initial acceleration, intermediate coordination, and final attenuation. This evolution is critically governed by the complex interplay of hydrodynamic shear stress exerted by the fluid flow, frictional resistance at the fracture walls, and dynamic interactions (collisions, contacts) between individual particles. Sensitivity analyses reveal that parameters like fracture roughness exert significant nonlinear control on transport efficiency, with an identified optimal JRC range (14–16) promoting the most effective particle transit. Hydraulic pressure and mean aperture size also exhibit strong, nonlinear regulatory influences. Particle transport manifests through characteristic collective migration patterns, including “overall bulk progression”, processes of “fragmentation followed by reaggregation”, and distinctive “center-stretch-edge-retention” formation. Simultaneously, specific behaviors for individual particles are categorized as navigating the “main shear channel”, experiencing “boundary-disturbance drift”, or becoming trapped as “wall-adhered obstructed” particles. Crucially, a robust multivariate regression model is formulated, integrating these key parameter effects, to quantitatively predict the critical migration time required for 80% of the total particle mass to transit the fracture. This investigation provides fundamental mechanistic insights into the particle–fluid dynamics underpinning hazardous water–sand inrush phenomena, offering valuable theoretical underpinnings for risk assessment and mitigation strategies in deep underground engineering operations. Full article

Against the backdrop of global commitments to sustainable development and carbon neutrality objectives, the agricultural sector faces compelling imperatives to transition toward environmentally sustainable and resource-efficient production systems. Focusing on the critical role of agricultural inputs, this study investigates how China’s Zero Growth Policy for Fertilizer and Pesticide Use (ZGP), implemented in 2015, influences green transformation in the agricultural inputs sector through a quasi-natural experiment framework. Employing a staggered difference-in-differences (DID) design with comprehensive nationwide firm registration data from 2013 to 2020, we provide novel micro-level evidence on environmental regulation’s market-shaping effects. Our findings demonstrate that the ZGP significantly enhances green market selection, stimulating entry of environmentally certified firms, with effect heterogeneity revealing policy impacts are attenuated in manufacturing-intensive regions due to green entry barriers, while being amplified in major grain-producing areas and more market-oriented regions. Mechanism analyses identify three key transmission channels: intensified regulatory oversight, heightened public environmental awareness, and growing market demand for sustainable inputs. Furthermore, the policy has induced structural transformation within the industry, progressively increasing green enterprises’ market share. These results offer valuable insights for designing targeted environmental governance mechanisms to facilitate sustainable transitions in agricultural input markets. Full article

This study presents an acoustic membrane design utilizing a thin foil sound resonance mechanism to enhance sound absorption and insulation performance. The membranes incorporate single-layer and double-layer structures featuring parallel foil square wedge-shaped coffers and a flat bottom panel, separated by air cavities. The enclosed air cavity significantly improves the sound insulation capability of the acoustic membrane. Parametric studies were conducted to investigate key factors affecting the sound transmission loss (STL) of the proposed acoustic membrane. The analysis examined the influence of foil thickness, substrate thickness, and back cavity depth on acoustic performance. Results demonstrate that the membrane structure enriches vibration modes in the 500–6000 Hz frequency range, exhibiting multiple acoustic attenuation peaks and broader noise reduction bandwidth (average STL of 40–55 dB across the researched frequency range) compared to conventional resonant cavities and membrane-type acoustic metamaterials. The STL characteristics can be tuned across different frequency bands by adjusting the back cavity depth, foil thickness, and substrate thickness. Experimental validation was performed through noise reduction tests on an air compressor pump. Comparative acoustic measurements confirmed the superior noise attenuation performance and practical applicability of the proposed membrane over conventional acoustic treatments. Compared to uniform foil resonators, the combination of plastic and steel materials with single-layer and double-layer membranes reduced the overall sound level (OA) by an additional 2–3 dB, thereby offering exceptional STL performance in the low- to medium-frequency range. These lightweight, easy-to-manufacture membranes exhibit considerable potential for noise control applications in household appliances and industrial settings. Full article

Doxorubicin (DOX) is an anthracycline chemotherapeutic agent that is clinically limited by doxorubicin-induced cardiotoxicity (DIC), with ferroptosis and apoptosis identified as key mechanisms. As an antioxidant enzyme, GPX4 undergoes ubiquitin-mediated degradation during myocardial ischemia–reperfusion injury; however, the role of its ubiquitination in DIC remains unclear. This study revealed that GPX4 undergoes ubiquitinated degradation during DIC, exacerbating ferroptosis and apoptosis in cardiomyocytes. NEDD4L was found to interact with GPX4, and its expression was upregulated in DOX-treated mouse myocardial tissues and cardiomyocytes. NEDD4L knockdown alleviated DIC, as well as ferroptosis and apoptosis in cardiomyocytes. Mechanistically, NEDD4L recognizes GPX4 through its WW domain and mediates K48-linked ubiquitination and degradation of GPX4 under DOX stimulation via its HECT domain. Knockdown of NEDD4L reduced DOX-induced GPX4 ubiquitination levels and subsequent degradation. Notably, while NEDD4L knockdown mitigated DOX-induced cell death, concurrent GPX4 knockdown attenuated this protective effect, indicating that GPX4 is a key downstream target of NEDD4L in regulating cardiomyocyte death. These findings identify NEDD4L as a potential therapeutic target for preventing and treating DIC. Full article

Oxidative stress is closely associated with diarrhea in piglets, and alleviating intestinal oxidative stress may emerge as an effective strategy for porcine diarrhea. Curcumin (Cur) and selenium (Se) are both well recognized for their potent antioxidant effects. This study established in vitro (IPEC-J2 cells) and in vivo (ICR mice) intestinal oxidative stress models to investigate the effects and mechanisms of Cur combined with Se in alleviating oxidative stress. The results showed that Cur and Se exhibited synergistic antioxidant effects in vitro, outperforming individual treatments. Additionally, pretreatment with Cur and Se significantly attenuated dextran sulfate sodium (DSS)-induced colitis in ICR mice and improved serum antioxidant indices. Specifically, the mRNA levels of Nrf2, HO-1, and NQO-1 were upregulated, while the mRNA levels of NF-κB, IL-1β, and TNF-α were downregulated in colonic tissues. Finally, the 16S rRNA sequencing showed that DSS reduced alpha diversity and increased Simpson indices, while Cur and Se restored diversity indices and normalized beta diversity. To summarize, Cur and Se synergistically alleviate oxidative stress in IPEC-J2 cells and ICR mice, demonstrating therapeutic potential for intestinal disorders in pigs. Full article

Background/Objectives: Children with Autism Spectrum Disorder (ASD) often display heightened sensitivity to simple auditory stimuli, but have difficulty discriminating and integrating multiple phonological features (segmental: consonants and vowels; suprasegmental: lexical tones) at the syllable level, which negatively impacts their communication. This study aims to investigate the neural basis of segmental, suprasegmental and combinatorial speech processing challenges in Mandarin-speaking children with ASD compared with typically developing (TD) peers. Methods: Thirty children with ASD and thirty TD peers will complete a multi-feature oddball paradigm to elicit auditory ERP during passive listening. Stimuli include syllables with single (e.g., vowel only), dual (e.g., vowel + tone), and triple (consonant + vowel + tone) phonological deviations. Neural responses will be analyzed using temporal principal component analysis (t-PCA) to isolate overlapping ERP components (early/late MMN), and representational similarity analysis (RSA) to assess group differences in neural representational structure across feature conditions. Expected Outcomes: We adopt a dual-framework approach to hypothesis generation. First, from a theory-driven perspective, we integrate three complementary models, Enhanced Perceptual Functioning (EPF), Weak Central Coherence (WCC), and the Neural Complexity Hypothesis (NCH), to account for auditory processing in ASD. Specifically, we hypothesize that ASD children will show enhanced or intact neural discriminatory responses to isolated segmental deviations (e.g., vowel), but attenuated or delayed responses to suprasegmental (e.g., tone) and multi-feature deviants, with the most severe disruptions occurring in complex, multi-feature conditions. Second, from an empirically grounded, data-driven perspective, we derive our central hypothesis directly from the mismatch negativity (MMN) literature, which suggests reduced MMN amplitudes (with the exception of vowel deviants) and prolonged latencies accompanied by a diminished left-hemisphere advantage across all speech feature types in ASD, with the most pronounced effects in complex, multi-feature conditions. Significance: By testing alternative hypotheses and predictions, this exploratory study will clarify the extent to which speech processing differences in ASD reflect cognitive biases (local vs. global, per EPF/WCC/NCH) versus speech-specific neurophysiological disruptions. Findings will advance our understanding of the sensory and integrative mechanisms underlying communication difficulties in ASD, particularly in tonal language contexts, and may inform the development of linguistically tailored interventions. Full article

As the primary bioactive flavonoid in Coreopsis tinctoria, okanin has emerged as a promising antioxidant compound of substantial pharmacological interest. However, its efficacy against UVA-mediated photoaging remains unexplored. This research investigated the molecular mechanism underlying the photoprotective activity of okanin against UVA-mediated photoaging. Network pharmacology was employed to predict the pharmacological mechanism of Coreopsis tinctoria in skin photoaging, which was then validated through in vivo and in vitro studies. In vitro experiments indicated that treatment with okanin alleviated oxidative damage, apoptosis and mitochondrial dysfunction in HaCaT cells exposed to UVA radiation. In addition, the interaction between okanin and SIRT3 was confirmed using molecular docking, SPR and DARTS assays. However, silencing SIRT3 with siRNA abolished the promoting effects of okanin on mitophagy genes, confirming that okanin protects HaCaT cells against UVA damage through SIRT3 regulation. In in vivo, okanin enhanced the expression of SIRT3 and FOXO3a in dorsal skin, mitigating UV-mediated skin damage. Taken together, our results suggest the protective effects of okanin against UV radiation in both HaCaT cells and mice induced, at least in part, by regulating SIRT3/FOXO3a/PINK1/Parkin signaling pathway. These findings highlight the potential of okanin for use in skin care products aimed at promoting skin repair following UVA exposure. Full article

Objectives: Chronic psychological stress among college students increases sensitivity to negative emotional stimuli. Emotion regulation, a critical coping mechanism, draws upon cognitive resources and may impair subsequent cognitive control. Physical exercise has been proposed as an effective intervention to enhance both emotional and cognitive functioning. This study investigated whether a 12-week structured exercise intervention could modulate emotion regulation outcomes and improve cognitive control in college students experiencing high psychological stress. Methods: Forty-seven college students, identified as highly stressed via the Chinese College Students Psychological Stress Scale, were randomly assigned to either an exercise group (n = 25) or a control group (n = 22). The exercise group participated in supervised rope-jumping sessions three times per week for 40 min, following ACSM guidelines, over 12 weeks. Before and after the intervention, participants completed tasks measuring two emotion regulation strategies—expressive suppression and cognitive reappraisal—and tasks assessing cognitive control. Results: A significant group × time × strategy interaction emerged for subjective emotional valence: following the intervention, the exercise group reported attenuated negative valence under expressive suppression. For subjective arousal, post-intervention ratings decreased under suppression but increased under reappraisal in the exercise group, suggesting strategy-specific modulation by physical activity. Regarding cognitive control, electrophysiological measures revealed that the P3 component showed a significant interaction: the exercise group exhibited enhanced P3 amplitudes in congruent versus incongruent conditions after the intervention. Moreover, P3 interference scores were significantly reduced post-intervention in the exercise group compared to both its pre-intervention baseline and the control group. Conclusions: A 12-week aerobic exercise intervention enhanced emotion regulation outcomes and improved cognitive control under high psychological stress. These findings underscore the utility of physical exercise as a non-pharmacological approach to bolster cognitive–affective resilience in young adults. Full article

Against the backdrop of accelerating global energy transition, developing high-performance energy-storage systems is crucial for achieving carbon neutrality. Traditional electrode materials are limited by a single densification storage mechanism and low conductivity, struggling to meet demands for high energy/power density and a long cycle life. Carbon/high-entropy alloy nanocomposites provide an innovative solution through multi-component synergistic effects and cross-scale structural design: the “cocktail effect” of high-entropy alloys confers excellent redox activity and structural stability, while the three-dimensional conductive network of the carbon skeleton enhances charge transfer efficiency. Together, they achieve synergistic enhancement via interfacial electron coupling, stress buffering, and dual storage mechanisms. This review systematically analyzes the charge storage/attenuation mechanisms and performance advantages of this composite material in diverse energy-storage devices (lithium-ion batteries, lithium-sulfur batteries, etc.), evaluates the characteristics and limitations of preparation techniques such as mechanical alloying and chemical vapor deposition, identifies five major challenges (including complex and costly synthesis, ambiguous interfacial interaction mechanisms, lagging theoretical research, performance-cost trade-offs, and slow industrialization processes), and prospectively proposes eight research directions (including multi-scale structural regulation and sustainable preparation technologies, etc.). Through interdisciplinary perspectives, this review aims to provide a theoretical foundation for deepening the understanding of carbon/high-entropy alloy composite energy-storage mechanisms and guiding industrial applications, thereby advancing breakthroughs in electrochemical energy-storage technology under the energy transition. Full article

The extensive utilization of amorphous silica nanoparticles (SiNPs) has raised concerns regarding the potential health risks. Previous studies have indicated that SiNPs could trigger both the activation of heat shock proteins (HSPs) and epithelial–mesenchymal transition (EMT) in BEAS-2B cells; however, the underlying mechanisms require further elucidation. This study aimed to investigate how SiNPs activate the heat shock response (HSR) in BEAS-2B cells, which subsequently triggers EMT. Firstly, we observed that SiNPs were internalized by BEAS-2B cells and localized in the endoplasmic reticulum (ER), inducing ER stress. The ER stress led to the activation of SIRT1 by phosphorylation, which enhanced the nuclear transcriptional activity of HSF1 via deacetylation. HSF1 was found to upregulate the levels of HSP70 and HSP27 proteins, which further affected EMT-related genes and, ultimately, induced EMT. Additionally, 4-phenylbutyric acid (4-PBA) inhibited ER stress, which attenuated the SIRT1/HSF1 signaling pathway. The knockdown of SIRT1 and HSF1 using siRNA effectively suppressed the EMT progression. In summary, these results suggested that SiNPs activated the SIRT1/HSF1/HSPs pathway through ER stress, thereby triggering EMT in BEAS-2B cells. The present study identified a novel mechanism of SiNP-induced EMT, which has provided valuable insights for future toxicity studies and risk assessments of SiNPs. Full article