Search Results (1,877)

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Full article

With the expansion of global oil and gas resource exploration and development into deep and ultra deep layers, the efficient development of deep carbonate rock fracture cave reservoirs has become the key to ensuring energy security. However, this type of reservoir commonly faces high temperatures, high salinity, and extremely strong heterogeneity, leading to increasingly severe water content spikes caused by dominant water flow channels. Although the existing traditional inorganic plugging agent has good temperature resistance, it has the defects of great brittleness and easy cracking, while the organic polymer gel is prone to degradation failure under high temperature and high salt environments. In order to solve the above problems, a new biochar-enhanced inorganic composite gel system was constructed by using biochar prepared from agricultural and forestry waste pyrolysis as a functional enhancement component. Through rheological testing, high-temperature and high-pressure mechanical experiments, long-term thermal stability evaluation, and dynamic sealing experiments of fractured rock cores, the reinforcement and toughening laws and rheological control mechanisms of biochar on inorganic matrices were systematically studied. Research has found that a biochar content of 0.5 wt% can significantly improve the micro pore structure of the matrix. By utilizing its micro aggregate filling effect and interfacial chemical bonding, the compressive strength of the solidified body can be increased to over 2 MPa, and there is no significant decline in strength after aging at 130 °C for 30 days. More importantly, the unique “adsorption slow-release” mechanism of biochar effectively stabilizes the hydration reaction kinetics at high temperatures, extending the solidification time of the system to 15 h and solving the problem of flash condensation in deep well pumping. This system exhibits excellent shear thinning characteristics and crack sealing ability, and presents a unique “yield reconstruction” toughness sealing feature. This study elucidates the multidimensional strengthening mechanism of biochar in inorganic cementitious materials, providing technical reference for stable oil and water control in deep fractured reservoirs. Full article

Wuzhishan pigs are a typical Chinese indigenous miniature pig breed, with thin skin and high amino acid content in muscle; slow weight gain and long feeding phases limit their value. As the primary digestive and absorptive organ, the intestine is crucial for growth, yet current studies on its development are limited. This study aimed to investigate intestinal physiological differences in Wuzhishan pigs across four phases (pre-weaning: 7, 14 days; weaning: 35, 38, 45 days; fattening: 70, 100 days; maturity: 180, 240 days) by evaluating intestinal morphology, digestive enzyme activity, gut microbiota diversity via 16S rRNA gene sequencing, and metabolite characteristics via metabolomic analysis. Results showed poor intestinal morphology and enzyme activity during weaning, significant ileal and colonic microbial diversity differences across phases, increased beneficial bacteria with age, and enriched opportunistic pathogens (Streptococcus, Romboutsia, Terrisporobacter) during weaning; weaning also had lower lipid metabolites, correlated with decreased Fusobacterium, Lactobacillus, and Muribaculaceae. Fattening enhanced amino acid metabolism, with increased Lactobacillus correlated with higher amino acids and muscle-related metabolites, while maturity increased immune-related metabolites (e.g., pyridoxine) in the vitamin B6 pathway. These results explain delayed rapid weight gain in Wuzhishan pigs and provide a theoretical basis for maintaining intestinal stability and production performance. Full article

Temporal preparation has been consistently shown to be driven by regular rhythms, which are commonly considered to automatically attract attentional resources to on-beat moments, facilitating behavioral performance relative to off-beat moments in both younger and older adults. However, when targets occur more often at off-beat moments such that the rhythm becomes task-disadvantageous, it remains unclear whether older adults can adjust preparatory resources away from on-beat moments and toward the high-probability time point. To address this issue, younger and older adults completed a temporal preparation task at fast (800 ms) and slow (2000 ms) tempos under three conditions: attend-on-beat (rhythmic sequence; 80% on-beat targets), attend-off-beat (rhythmic sequence; 80% off-beat targets), and random (nonrhythmic sequence; 50% each). The results showed that, relative to the random condition, both age groups responded faster at the instructed high-probability time point in both rhythmic conditions, even when it fell off-beat, indicating that temporal probabilities can guide temporal preparation away from a task-disadvantageous on-beat moment toward the task-relevant time point. Moreover, this pattern was observed under both the fast and slow tempos. Together, these findings suggest that older adults preserve the ability to use temporal probabilities to reduce rhythmic distraction across sub-second and supra-second time scales. Full article

One of the strategies for the control and elimination of schistosomiasis is the control of its snail vectors in an endemic area, as is done in other tropical diseases like malaria. However, the strategy currently practiced for the control of the disease in Nigeria is the annual mass administration of preventive chemotherapy (Praziquantel) among school-age children while neglecting the control of its snail intermediate host and other control components. The neglect of malacology and vector control will slow the elimination targets and timeline of 2030 set by the WHO. In this study, we investigated the abundance and seasonal variations in the snail vectors of schistosomiasis and the relationship between the disease among humans and infected snail vectors. A total of 21,282 snails were collected from 13 sites across the six area councils of the Federal Capital Territory (FCT). Of the collected snails, 1451 (6.8%) belong to three species: Biomphelaria pfeifferi (0.5%), Bulinus truncatus (2.1%) and Bulinus globosus (4.2%), which are known to be vectors of Schistosoma mansoni, Schistosoma haematobium and Schistosoma bovis, respectively. These three species were all shedding cercariae both at the time of collection and afterwards, when they were induced to shed cercariae. The association between the reported prevalence of the disease and the percentage of snails shedding cercaria were heterogenous across different communities. While Takushara, with a disease prevalence of 46%, had 60% of the cercaria shedding snails, Kwaita sabo pukafa and Guduji, with disease prevalences of 56% and 26% respectively, had no cercaria shedding snails. Similarly, Dagiri rafin shahu and Gwako 1, with disease prevalences of 60% and 38%, had cercaria shedding snails of less than 1%. Nonetheless, the presence of Bulinus and Biomphelaria species in these communities indicates a potential risk of infection for humans and other animals who may come in contact with the water. Consequently, integrated multisectoral control and elimination measures that combine malacological monitoring with behavioral, environmental, and historical epidemiological assessments with a deliberate health orientation of the people through sensitization and health education is advocated to reduce exposure to the disease risk factors and contribute towards elimination of the disease. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions—particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients—have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut–eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD. Full article

Infectious diseases remain a major cause of mortality and disability worldwide. This burden is driven, in part, by antimicrobial resistance (AMR) and the re-emergence of epidemic and pandemic threats, underscoring the need for translational research to address knowledge gaps exposed by recent pandemics. Despite significant advances enabled by antibiotics and antivirals, their effectiveness is increasingly constrained by resistance development, limited pathogen spectra, and prolonged development timelines that fail to keep pace with rapidly shifting epidemiology. Diagnostic limitations impede timely pathogen identification and hinder the development of treatment regimens informed by pathogen mechanisms of action. Severe infections frequently involve dysregulated host responses, including hyperinflammation, inflammasome activation, and endothelial or immunothrombotic injury, which may progress to sepsis, immunoparalysis, or chronic sequelae, highlighting the limitations of pathogen-centered paradigms. Conventional biomarkers and culture-based microbiology are often slow or nonspecific, while molecular assays may not reliably distinguish colonization from active infection or capture host-response heterogeneity shaped by age, immune competence, and disease stage. This review synthesizes mechanistic and translational insights across three interrelated axes: (i) host–pathogen interactions, with a focus on innate immune sensing networks (e.g., Toll-like receptors, inflammasomes, RIG-I-like receptors, and cGAS-STING) and microbial replication and immune evasion strategies; (ii) clinical and public health implications, spanning acute organ dysfunction syndromes, post-acute infection syndromes, and AMR-driven health system strain; and (iii) emerging therapeutics along a continuum of pathogen-, virulence-, host-, and immune-directed approaches. Emphasis is placed on anti-virulence therapeutics, bacteriophage therapy, monoclonal antibodies, and engineered immune modalities within frameworks of quantitative translational pharmacology and implementation science. Finally, an integrative conceptual framework encompassing mechanistic phenotypes, host-response diagnostics, and stage-adapted therapeutic combinations is proposed to guide rational intervention across endemic infections and future pandemic preparedness. Full article

Understanding the spatial mismatch between population distribution and economic activities is central to regional development, particularly in large river basins experiencing rapid demographic change. Existing studies often rely on slow-moving structural variables and give limited attention to dynamic population processes. This study examines the spatiotemporal patterns, demographic mechanisms, and regional heterogeneity of population–economy mismatch in the Yellow River Basin from 2000 to 2020. We hypothesize that population–economy mismatch exhibits pronounced spatial heterogeneity across the upper, middle, and lower reaches of the basin, and that demographic structure and migration dynamics play a decisive role in shaping these patterns. Using county-level data, we construct a Population–Economy Distribution Disparity Ratio R, apply decomposable Theil indices, and estimate two-way fixed-effects panel models incorporating demographic and migration indicators. Spatial econometric models are further employed as robustness checks. The results show that intra-regional disparities account for more than 97% of total population–economy mismatch, while inter-regional differences remain limited. Population migration intensity and age structure significantly influence mismatch dynamics, with effects varying systematically along the basin gradient. These findings underscore the importance of integrating dynamic demographic processes into spatial mismatch analysis and support regionally differentiated and systemically coordinated policy interventions for high-quality development in the Yellow River Basin. Full article

Tuberculosis (TB) remains a major public health challenge in China despite substantial long-term progress. Using data from the Global Burden of Disease Study 2023, this study reassessed trends and determinants of TB burden in China from 1990 to 2023. Age-standardized incidence, mortality, and disability-adjusted life year (DALY) rates were analyzed using estimated annual percentage change, age–period–cohort modeling, and demographic decomposition, with comparative risk assessment to quantify behavioral and metabolic contributions. Between 1990 and 2023, age-standardized incidence, mortality, and DALY rates declined by approximately 73.24%, 94.00%, and 92.40%, respectively. Negative net and local drift values indicated sustained reductions across age groups; however, the decline slowed after 2021, with a modest rebound in incidence. Since 2015, reductions in incidence have been more moderate than the pace required to achieve the 2035 End TB Strategy targets. Decomposition analysis demonstrated that improvements in age-specific rates were the primary drivers of long-term reductions, whereas demographic shifts—particularly population aging—partially offset these gains. The burden increasingly shifted toward older adults, and males consistently experienced higher rates than females. Tobacco and alcohol use contributed substantially to sex differentials, while undernutrition and metabolic disorders remained relevant risk factors. These findings indicate that China’s TB epidemic has entered a phase shaped by demographic aging and evolving risk structures, requiring sustained and adaptive control efforts. Full article

The Jiaodong Peninsula hosts one of the largest gold provinces in the world. The Xincheng gold deposit, located within the Jiaojia gold metallogenic belt, is the largest deposit in this belt and represents a super-large fractured alteration-type gold deposit hosted in fracture zones with relatively well-preserved conditions. Mineralization and hydrothermal alteration are controlled by the Jiaojia Fault zone and its subsidiary faults. The Jiaojia Fault (JJF) serves as the principal ore-hosting structure of the Xincheng deposit, and its multi-stage activity has governed the mineralization, subsequent modification, and preservation of the deposit. However, the post-mineralization cooling, uplift, and exhumation history of the deposit remains poorly constrained. In this study, zircon and apatite fission-track thermochronology analyses were conducted, and inverse thermal history modeling of apatite was performed to reconstruct the tectonic-metallogenic evolution of the Xincheng gold deposit. The zircon fission-track ages range from 90.0 ± 4.0 to 118.0 ± 5.2 Ma, which are younger than the mineralization age (~120 Ma), indicating that the region experienced widespread cooling during the Late Early Cretaceous. This cooling event was likely related to crustal uplift and exhumation triggered by a transformation of the tectonic regime. The apatite fission-track ages range from 15 ± 1.8 to 38 ± 2.7 Ma, recording the Cenozoic cooling and uplift history after mineralization. The inverse thermal history modeling results show that the post-mineralization cooling process can be divided into three stages. The first stage, from 42 ± 5 to 30 ± 4 Ma, is characterized by rapid cooling, with an average cooling rate of 4.23 °C/Myr. The second stage, from 30 ± 4 to 12 Ma, represents a period of slow cooling, with an average cooling rate of 0.98 °C/Myr. Since 12 Ma, the third stage has been marked by renewed rapid cooling, with an average cooling rate of 4.17 °C/Myr. Variations in cooling rates among different stages reflect adjustments in the regional tectonic stress field and the influence of activity along the JJF. Based on the fission track thermochronological data and a reasonable estimate of the geothermal gradient, the total amount of exhumation since 120 Ma is calculated to be approximately 8.22 km. Integration of these results indicates that the shallow portion of the deposit has undergone a certain degree of erosion; however, the overall preservation conditions remain favorable, and significant exploration potential persists at depth and along strike. This study constrains the post-mineralization cooling and erosion history of the Xincheng gold deposit, reveals the controlling role of multi-stage tectonic activity on deposit preservation, and provides new temporal constraints and a scientific basis for preservation assessment and deep exploration of gold deposits in the Jiaodong Peninsula and in regions with similar tectonic settings. Full article

Metformin has stood as the primary clinical tool for type 2 diabetes for decades, yet its potential reach into oncology and gerontology is only now being critically dissected. This review evaluates how metformin might actually pull the levers of cancer progression and biological aging. Evidence from across various models suggests that the drug works by recalibrating cellular energy homeostasis—specifically by triggering AMPK and dampening the mTOR pathway. This signaling shift ripples through downstream processes like autophagy and oxidative stress regulation, theoretically slowing tumor growth and pushing back against cellular senescence. However, our look at the literature from PubMed, Scopus, and Web of Science shows a messy reality where preclinical success often stalls during clinical translation. Even though observational data point toward lower cancer rates in diabetic cohorts, these “wins” are frequently skewed by clinical confounders and inconsistent data. This makes the leap from metabolic control to a broad-spectrum anti-aging or anticancer therapy a point of serious contention. We argue that only large-scale, randomized trials can truly verify if metformin is safe and effective for non-diabetic populations. In the end, untangling these molecular routes is the only way to see if metformin belongs in future oncological or healthy aging strategies. That being said, at least mechanistically, metformin definitely offers potential that warrants such large-scale research. Full article

This study investigates the solution and artificial aging processes of TiB₂/7050 composites. Using microscopic and mechanical tests, we systematically evaluate the material’s microstructural evolution and mechanical performance, aiming to optimize heat treatment parameters. The study shows that a solution temperature of 475 °C for 1 h is optimal for fully dissolving the second-phase particles. Regarding artificial aging, peak hardness of 246 HV is achieved at 140 °C for 16 h. Analysis of the phases and microstructure in O and T6-states shows that strengthening occurs through grain boundary hardening and precipitation hardening. The effect of TiB₂ particles on the above process was also explored. During solidification, TiB₂ particles were pushed by the advancing solid–liquid interface and primarily distributed along grain boundaries. This distribution subsequently slowed the solid solution process by reducing the contact area between the η(MgZn₂) phase and the α(Al) matrix. During aging, they enhance grain boundary precipitates (GBPs) in particle-rich regions and inhibit the formation of precipitate-free zones (PFZs), with a concentration of the η’ phase forming around the particles. Beyond a certain distance from the particles, there is a decrease in η’ phase concentration. This study is expected to contribute to advanced lightweight materials research and development, opening up new opportunities for their application in various industries. Full article

Background/Objectives: Active surveillance (AS) has emerged as a safe alternative to primary therapy for low- and select intermediate-risk prostate cancer (PCa), but optimal patient selection and surveillance strategies remain challenging due to limited risk stratification tools enabling early detection of lesions with high potential for histopathological progression. This study presents an integrated method for predicting prostate cancer progression within 12 months, aiming to improve AS patient selection by categorizing patients into two risk groups: rapid progressors who would benefit from immediate treatment and slow progressors suitable for AS. Methods: The risk assessment platform combines convolutional neural networks for automatic segmentation of prostate and suspicious-for-cancer lesions on multiparametric MRI (mpMRI) with logistic regression to estimate progression risk. The networks were trained on annotated lesions from radical prostatectomy specimen mapped to mpMRI. The prediction model incorporated pre-biopsy clinical variables (age, PSA, PI-RADS) and MRI-derived intratumoral radiomic features from 163 participants of a prospective clinical trial, using histopathological progression within 12 months as endpoint. Results: The clinical-radiomics model achieved an AUC of 0.84 in distinguishing rapid from slow progressors, using non-invasive monitoring techniques. In an independent test set, the model significantly improved AS patient selection, increasing negative predictive value by 18.5% compared to current standard-of-care (p < 0.001). Conclusions: The risk assessment platform shows promise for use during annual follow-up visits to reliably differentiate suitable AS candidates with stable disease from PCa patients who are likely to experience early progression. Full article

Background: Fibromyalgia (FM) is a chronic widespread pain condition implicated in accelerated aging, functional decline, and physical frailty. Objective: This study examined differences in performance-based and self-reported physical frailty phenotypes among middle-aged and older adults with and without FM. Materials and Methods: A cross-sectional sample of 234 community-dwelling middle-aged and older adults with (59.0%) or without FM was analyzed. Physical frailty was defined as weakness, low physical activity, exhaustion, and slowness, assessed using validated performance-based (Fullerton Advanced Balance Scale [FAB], 8-foot up and go test [8FUPGT], 30-second chair stand [30SCS], 6-minute walk [6MWT], 30-foot walk [30FW]) and self-report measures (Rapid Assessment of Physical Activity [RAPA], fatigue numeric rating scale). Principal component analysis (PCA) evaluated the underlying structure of physical frailty indicators, yielding performance-based and self-reported components. Standardized factor scores were used as outcomes in regression analyses examining associations with pain intensity. Results: PCA supported a two-component frailty structure explaining 61% of the variance. After adjusting for age, gender, depressive symptoms, and body mass index, greater pain intensity was associated with worse performance-based (B = −0.10, p < 0.001; adjusted R² = 0.36) and self-reported (B = −0.10, p < 0.001; adjusted R² = 0.39) frailty. Discussion: Findings suggest that pain intensity is associated with frailty risk among aging adults, supporting the clinical utility of both performance-based and self-reported physical frailty assessments in FM. Full article

Background/Objectives: Dynamic changes in inorganic phosphate (Pi), phosphocreatine (PCr), and pH during post-exercise recovery reflect underlying muscle energetics and mitochondrial ATP synthesis, but the conventional single-pool model assuming uniform metabolic response fails to address myofiber composition and pH-dependent metabolic heterogeneity in skeletal muscle. This study aimed to characterize the interplay between pH, Pi, and PCr, and to develop an analytical method for assessing pH-resolved ATP synthesis using ³¹P MRS. Methods: Five healthy subjects underwent dynamic ³¹P MRS scans during plantar flexion exercise. ATP synthesis was evaluated from post-exercise PCr and Pi recovery time courses using the single-pool model, and from Pi recovery time courses using a multi-pool model in which the Pi signal lineshape was segmented into four pH-specific pools: alkaline (pH 7.3 ± 0.2), neutral (pH 7.0 ± 0.1), mildly acidic (pH 6.8 ± 0.1), and moderately acidic (pH 6.6 ± 0.1). Results: The single-pool model showed that during exercise, Pi increased proportionally to PCr depletion, and both Pi and PCr recovered monoexponentially immediately after exercise with ${\tau }_{\mathrm{Pi}} \left(33\pm 9 \mathrm{s}\right)<{\tau }_{\mathrm{PCr}} (40 \pm 9 \mathrm{s})$; ATP remained stable while pH exhibited a “heart-beat” pattern, characterized by an initial alkalization followed by neutralization during exercise, a post-exercise acidic undershoot, and a subsequent slow recovery (${\tau }_{\mathrm{pH}}\gg {\tau }_{\mathrm{PCr}}$). The four-pool model demonstrated a pronounced pH dependence of Pi recovery, with slower recovery at lower pH (${\tau }_{\mathrm{Pi}}$: 19 ± 6 s at pH 7.3, 25 ± 7 s at pH 7.0, 32 ± 11 s at pH 6.8, and 46 ± 17 s at pH 6.6). Pi recovery is slowed with aging under acidic conditions, with little or no effect observed at neutral or alkaline pH. These results provide new insights into skeletal muscle metabolic heterogeneity, reflecting how different myofiber microenvironments modulate ATP synthesis. Conclusions: By overcoming the constraints of the single-pool model, the proposed multi-pool framework uncovers pH-dependent ATP synthesis and provides direct evidence of pronounced metabolic heterogeneity in skeletal muscle during exercise and recovery. Full article