Search Results (18,045)

Advances in geroscience suggest that aging is modulated by molecular pathways that are amenable to dietary and pharmacological intervention. We conducted an integrative critical review of caloric restriction (CR), intermittent fasting (IF), and caloric restriction mimetics (CR-mimetics) to compare shared mechanisms, clinical evidence, limitations, and translational potential. Across modalities, CR and IF consistently activate AMP-activated protein kinase and sirtuins, inhibit mTOR (mechanistic target of rapamycin) signaling, and enhance autophagy, aligning with improvements in insulin sensitivity, lipid profile, low-grade inflammation, and selected epigenetic aging measures in humans. CR-mimetics, such as metformin, resveratrol, rapamycin, and spermidine, partially reproduce these effects; however, long-term safety and efficacy in healthy populations remain incompletely defined. Methodological constraints—short trial duration, selective samples, intermediate (nonclinical) endpoints, and limited adherence monitoring—impede definitive conclusions on hard outcomes (frailty, disability, hospitalization, mortality). We propose the Active Management of Aging and Longevity (AMAL) model, a three-level biomarker-guided framework that integrates personalized diet, chrono-nutrition, exercise, and the selective use of CR-mimetics, along with digital monitoring and decision support. AMAL emphasizes epigenetic clocks, multi-omics profiling, inflammatory and microbiome metrics, and adaptive protocols to enhance adherence and clinical relevance. Overall, CR, IF, and CR mimetics constitute promising, complementary strategies to modulate biological aging; rigorous long-term trials with standardized biomarkers and clinically meaningful endpoints are needed to enable their scalable implementation. Full article

Background: Glutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression of GLT-1 following TBI remain poorly understood. After TBI, the endocannabinoid 2-arachidonoyl glycerol (2-AG) is elevated several times. 2-AG is known to inhibit key positive transcriptional regulators of GLT-1. This study aims to investigate the role of 2-AG in regulating GLT-1 expression and to uncover the underlying mechanisms involved. Methods: A controlled cortical impact (CCI) model was used to establish a TBI model in C57BL/6J mice. The CB1 receptor antagonist (referred to as AM281) and the monoacylglycerol lipase (MAGL) inhibitor (referred to as JZL184) were administered to investigate the role and mechanism of 2-AG in regulating GLT-1 expression following TBI. Behavioral tests were conducted to assess neurological functions, including the open field, Y-maze, and novel object recognition tests. Apoptotic cells were identified using the TUNEL assay, while Western blot analysis and immunofluorescence were employed to determine protein expression levels. Results: The expression of GLT-1 in the contused cortex and hippocampus following TBI showed an initial decrease, followed by a gradual recovery. It began to decrease within half an hour, reached its lowest level at 2 h, and then gradually increased, returning to normal levels by 7 days. The administration of AM281 alleviated neuronal death, improved cognitive function, and reversed the reduction of GLT-1 caused by TBI in vivo. Furthermore, 2-AG decreased GLT-1 expression in astrocytes through the CB1-CREB signaling pathway. Mechanistically, 2-AG activated CB1, which inhibited CREB phosphorylation in astrocytes. This decreased GLT-1 levels and ultimately increased neuronal sensitivity to glutamate excitotoxicity. Conclusions: Our research demonstrated that the upregulation of GLT-1 expression effectively mitigated neuronal apoptosis and cognitive dysfunction by inhibiting the CB1-CREB signaling pathway. This finding may offer a promising therapeutic strategy for TBI. Full article

The article deals with the analysis of the mechanical properties of the newly designed aluminum alloy Al-Si7CrMnCu2.5. The research was carried out in order to map a new alloy with a certain addition of chromium and manganese from the point of view of mechanical properties and their changes after heat treatment (hardening, artificial aging) with defined parameters. Specifically, properties such as strength limit, yield strength, ductility, hardness, and microhardness were analyzed, both in the cast state and after heat treatment. The alloy was designed as an alternative to the standard Al-Si alloys already used in practice (AlSi7Mg, AlSi7Mg0.3, AlSi8Cu2Mn, AlSi8Cu3), which are mainly used in the production of engine parts and other components for the automotive and aviation industries. As can be seen from the presented results, the experimental AlSi7CrMnCu2.5 alloy exceeds the properties of the other selected alloys by tens of percent already in the cast state in many parameters. After heat treatment, the results achieved are comparable to the mentioned alloys, and in most cases, their values exceed them, especially in terms of ductility and hardness. Full article

Traditional liquid electrolyte batteries face safety concerns such as leakage and flammability, while further optimization has reached a bottleneck. Solid electrolytes are therefore considered a promising solution. Here, a PEO–LiTFSI–LATP (PELT) composite electrolyte was developed by incorporating nanosized Li_1.3Al_0.3Ti_1.7(PO₄)₃ fillers into a polyethylene oxide matrix, effectively reducing crystallinity, enhancing mechanical robustness, and providing additional Li⁺ transport channels. The PELT electrolyte exhibited an electrochemical stability window of 4.9 V, an ionic conductivity of 1.2 × 10⁻⁴ S·cm⁻¹ at 60 °C, and a Li⁺ transference number (tLi+) of 0.46, supporting stable Li plating/stripping for over 600 h in symmetric batteries. More importantly, to address poor electrode–electrolyte contact in conventional layered cells, we proposed an integrated electrode–electrolyte architecture by in situ coating the PELT precursor directly onto LiFePO₄ cathodes. This design minimized interfacial impedance, improved ion transport, and enhanced electrochemical stability. The integrated PELT/LFP battery retained 74% of its capacity after 200 cycles at 1 A·g⁻¹ and showed superior rate capability compared with sandwich-type batteries. These results highlight that coupling LATP-enhanced polymer electrolytes with an integrated architecture is a promising pathway toward high-safety, high-performance solid-state lithium-ion batteries. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency following primary infection, residing within myeloid progenitor cells and monocytes. To achieve this, the virus employs multiple immune evasion strategies. It suppresses innate immune signaling by inhibiting Toll-like receptor and cGAS-STING pathways. In addition, the virus suppresses major histocompatibility complex (MHC)-dependent antigen presentation to evade T cell recognition. As the downregulation of MHC molecules may trigger NK cell activation, the virus compensates for this by expressing proteins such as UL40 and IL-10, which engage inhibitory NK cell receptors and block activating signals, thereby suppressing NK cell immune surveillance. Viral proteins like UL36 and UL37 block host cell apoptosis and necroptosis, allowing HCMV to persist undetected and avoid clearance. In settings of profound immunosuppression, such as after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation, slow immune reconstitution creates a window for viral reactivation. Likewise, immunosenescence and chronic low-grade inflammation during aging increases the risk of reactivation. Once reactivated, HCMV triggers programmed cell death, releasing viral PAMPs (pathogen-associated molecular patterns) and host-derived DAMPs (damage-associated molecular patterns). This release fuels a potent inflammatory response, promoting further viral reactivation and exacerbating tissue damage, creating a vicious cycle. This cycle of inflammation and reactivation contributes to both transplant-related complications and the decline of antiviral immunity in the elderly. Therefore, understanding the immune regulatory mechanisms that govern the switch from latency to reactivation is critical, especially within the unique immune landscapes of transplantation and aging. Elucidating these pathways is essential for developing strategies to prevent and treat HCMV-related disease in these high-risk populations. Full article

Dye-contaminated wastewater has become one of the most severe environmental challenges due to the non-biodegradability and toxicity of synthetic dyes. While photocatalytic degradation is considered a green and efficient technology for wastewater purification, conventional TiO₂ suffers from limited light utilization and rapid electron–hole recombination. In this exploration, Ag-TiO₂-RGO nanocomposites were successfully fabricated and systematically investigated by XRD, SEM, TEM, XPS, Raman, and PL spectroscopy. The incorporation of Ag nanoparticles and reduced graphene oxide (RGO) synergistically improved charge separation and transfer efficiency. Photocatalytic activity was evaluated using different dyes as pollutants under visible light irradiation. Among the samples, Ag-TiO₂-RGO-3% exhibited the highest RhB degradation efficiency of 99.5% within 75 min, with a rate constant (K) of 0.05420 min⁻¹, which was nearly three times higher than that of pure TiO₂. The photocatalyst also showed excellent reusability with only minor efficiency loss after five cycles, and its activity remained stable across a wide pH range. Radical trapping experiments revealed that •O₂⁻ served as the dominant reactive species, with additional contributions from •OH and photogenerated holes (h⁺). A possible photocatalytic mechanism was proposed, in which Ag nanoparticles and RGO effectively suppressed electron–hole recombination and accelerated the formation of reactive oxygen species for efficient dye mineralization. These findings demonstrate that Ag-TiO₂-RGO-3% is a promising photocatalyst with high activity, stability, and environmental adaptability for wastewater remediation. Full article

The ovary is among the earliest organs to undergo age-related degeneration, limiting the reproductive potential of elite horses and constraining the growth of the equine industry. Follicular development during estrus is a key determinant of fertility, yet the molecular mechanisms underlying its decline, particularly at the level of specific ovarian cell types, remain poorly understood in equids. Here, we constructed a single-cell transcriptomic atlas to investigate ovarian changes in Kazakh horses. Using single-cell RNA sequencing (scRNA-seq), we profiled 112,861 cells from follicle-containing and follicle-absent ovaries, identifying nine distinct ovarian cell types and their subtypes, each with distinct gene expression signatures. Functional enrichment analyses revealed cell type-specific engagement in biological pathways, including ECM–receptor interaction, PI3K-Akt signaling, and oxytocin signaling. Gene expression patterns indicated tightly regulated processes of ovarian activation and cell differentiation. Notably, stromal cells exhibited high expression of ROBO2, LOC111770199, and TMTC2, while smooth muscle cells (SMCs) were marked by elevated levels of CCL5, KLRD1, and NKG7. Moreover, cell–cell interaction analyses revealed robust signaling interactions among SMCs, endothelial cells, neurons, and proliferating (cycling) cells. Together, these findings provide a comprehensive single-cell transcriptomic map of normal and abnormal ovarian states during estrus in Kazakh horses, offering novel insights into the cellular mechanisms of follicular development and identifying potential diagnostic biomarkers and therapeutic targets for ovarian quiescence in equids. Full article

Eukaryotic cells respond to oxidative stress (OS), a physiological condition characterized by the accumulation of reactive oxygen species (ROS), through various protective mechanisms. The antioxidant defense system (ADS) is activated either by post-translational modifications of pre-existing proteins or through the induction of gene expression. These mechanisms protect cellular biomolecules against ROS damage. Although extensive research has been conducted in different species, there is limited information regarding the specific response of Yarrowia lipolytica to OS. This study aims to elucidate the molecular mechanisms by which Y. lipolytica responds to OS by analyzing the expression of genes encoding enzymes involved in antioxidant response, such as superoxide dismutase (Sod), catalase (Cat), and glutathione peroxidase (Gpx). The Y. lipolytica genome contains three CAT genes, one SOD gene, one copper chaperone for Sod (CCS) gene, and one GPX gene. The expression profiles of these genes were assessed in Y. lipolytica cells exposed to H₂O₂ [5 mM] over time. All genes reached their maximal expression within the first 15 min of exposure. Comparative analysis between young and aged Y. lipolytica cells subjected to OS revealed that young cells exhibited higher expression levels for all genes, with CAT3 and SOD showing the highest expression values. These findings suggest that the enzymes encoded by these genes play a crucial role in the antioxidant response of this species. To our knowledge, this is the first study demonstrating that the ADS in Y. lipolytica is regulated at the transcriptional level. Full article

Background: Basketball is characterized as a high-intensity, intermittent sport that places considerable demands on the cardiorespiratory, neuromuscular, and mechanical systems. These physiological requirements are modulated by contextual variables and the athlete’s stage of biological maturation, both of which significantly influence physical fitness outcomes. Consequently, it is imperative to employ age- and development-specific assessment protocols. Objectives: This study aimed to evaluate the differences in physical fitness across competitive categories and to explore the interrelationships among the various physical assessment tests. Twenty-four male players (U14 = 12; U16 = 12) participated in this research. Methods: Athletes were monitored using WIMUPRO inertial measurement units and completed the SBAFIT test battery to evaluate physical fitness parameters. Statistical analyses included both inferential and correlational approaches, with effect sizes calculated for all relevant variables. The independent variable was the competitive age category of the players. Results: The results indicated notable differences in physical performance between developmental groups, primarily attributed to biological maturation. Significant disparities were observed in measures of aerobic capacity, linear speed, agility, and centripetal force. Conclusions: The comparative nature of this study across developmental categories offers novel insights and practical implications for talent development and training optimization. Full article

Generative artificial intelligence (GenAI) holds significant potential to enhance university students’ learning. However, over-reliance on it to complete academic tasks poses a risk to academic achievement by potentially encouraging cognitive outsourcing. Despite this growing concern and an expanding body of research on GenAI usage, the mechanisms through which GenAI dependency and perceived teacher caring affect their academic achievement and self-efficacy remain underexplored. Based on the theory of media system dependence, this study explores the mechanisms through which university students’ dependency on GenAI affects their academic outcomes, focusing on the mediating role of self-efficacy and moderating role of perceived teacher caring. A survey was conducted with 418 university students from Chinese public universities who had used GenAI for an extended period. The results revealed that GenAI dependency positively predicts false self-efficacy and negatively predicts academic achievement, exhibiting a significant Dunning–Kruger effect. Perceived teacher caring moderates the relationship between GenAI dependency and self-efficacy. High perceived teacher caring mitigates the Dunning–Kruger effect but has a weak moderating effect on academic achievement. These findings enhance the explanatory power of the media system dependency theory in educational contexts and reveal the pathways through which GenAI dependency and teacher caring affect learning processes and outcomes. This study expands the theoretical implications of teacher caring in the digital age and provides empirical evidence to aid higher education administrators in optimising AI governance and teachers in improving instructional interventions. Full article

In this paper, Distribution of Relaxation Time (DRT) analysis is presented as a powerful tool for understanding the aging mechanisms in lithium-ion batteries, with a focus on its application to estimating the State of Health (SOH). A novel parameter, the characteristic relaxation time, derived from DRT analysis, is introduced to enhance SOH estimation. By analyzing the ratio of the central relaxation time (τ) between the charge transfer and diffusion peaks, the battery status can be determined without the need for historical data. Experimental data from lithium-ion batteries, including 18650 cells and LR2032 coin cells, were examined until the end of their life. Nyquist and DRT plots across various frequency ranges revealed consistent aging trends, particularly in the charge transfer and diffusion processes. These processes appeared as shifting and merging peaks in the DRT plots, signifying progressive degradation. A polynomial equation fitted to the τ ratio graph achieved a high accuracy (Adj. R² = 0.9994), enabling reliable battery lifespan prediction. Validation with a Samsung Galaxy S9+ battery demonstrated that the method could estimate its remaining life, predicting a total lifespan of approximately 2100 cycles (compared to 1000 cycles already completed). These results confirm that SOH estimation is feasible without prior data and highlight the potential of DRT analysis for accurate and quantitative prediction of battery longevity. Full article

In lithium-ion battery charging, balancing charging speed with efficiency and state of health (SOH) is paramount. First, a multi-state electric-thermal-aging coupling model was developed to accurately reflect battery operating conditions. Second, a voltage-based multi-stage constant current-constant voltage (VMCC-CV) strategy was implemented, incorporating an innovative V-SOC-R_int conversion mechanism—integrating voltage, state of charge (SOC), and internal resistance—to effectively mitigate thermal buildup during transitions. To optimize the VMCC-CV currents, an innovative enhancement was applied to the moth-flame optimization (MFO) algorithm, demonstrating superior performance over its traditional counterpart across diverse charging scenarios. Finally, three practical strategies were devised: rapid charging, multi-objective balanced charging, and enhanced safety performance charging. Relative to the manufacturer’s 0.75 C-CCCV protocol, the balanced strategy significantly accelerates charging, reducing time by 34.11%, while sustaining 93.54% efficiency and limiting SOH degradation to 0.006856%. Compared to conventional CCCV methods, the proposed approach offers greater versatility and applicability in varied real-world scenarios. Full article

The phase shift (PS) between spontaneous slow oscillations of cerebral and systemic hemodynamics reliably reflects the state of cerebral autoregulation (CA). However, CA measurements are performed retrospectively after studying the signals from the analysis sensors. At the same time, CA-oriented therapy is becoming increasingly important with the receipt of data on the state of CA in real time, especially in intensive care units. We offer a hardware and software complex for transcranial Dopplerography, which uses a non-invasive method and allows for continuous measurement of cerebral blood flow to assess the rate of CA in real time. The hardware and software complex uses sensors to measure the PS between spontaneous slow oscillations of blood flow velocity (BFV) in the middle cerebral arteries (MCAs) and systemic arterial pressure (BP) in the Mayer wave range and performs wavelet analysis of sensor signals. An examination of 30 volunteers, with an average age of 28 ± 8 years, and 15 patients, with an average age of 57 ± 16 years, with various neurovascular pathologies confirms the feasibility of using the developed hardware and software complex for continuous monitoring of PS in real time to study the mechanisms of cerebral blood flow regulation. Full article

The cold-rolled 2024 aluminum alloy sheets were subjected to solution treatments at different temperatures followed by artificial aging. The microstructure and mechanical properties were investigated using Vickers microhardness testing, tensile testing, optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results indicate that as the solution temperature increases, the coarse particles gradually dissolved into the matrix. At a solution temperature of 500 °C, the grains become nearly equiaxed with an average size of ~16.47 μm, and no significant grain growth is observed compared to the as-rolled condition. The refined microstructure contributes to excellent mechanical properties. In contrast, when the solution temperature increases to 550 °C, the microstructure shows severe grain coarsening (up to ~61.39 μm), which indicates that overburning occurs, resulting in a drastic deterioration in mechanical performance. As the aging time increases, precipitates become more uniformly and densely distributed throughout the matrix, and the hardness initially increases and reaches a peak after approximately 6 h of aging at 180 °C. The optimal mechanical performance, characterized by a favorable combination of strength and ductility, is achieved at an aging time of 6 h. In summary, the optimal heat treatment condition for the cold-rolled 2024 aluminum alloy sheet is solution treatment at 500 °C for 1 h followed by aging at 180 °C for 6 h, resulting in a hardness of 154 HV, a tensile strength of 465 MPa and an elongation of 13%. Full article

Existing research on live-streaming e-commerce consumption behavior is mostly limited by a single disciplinary framework, unable to systematically parse the mechanism of macro-policies and cultural values on intergenerational consumer psychology. This study takes ASEAN cross-border live-streaming e-commerce as a scenario, integrates theories of economics, political science, and sociology, and constructs an innovative three-layer analysis model of “macroeconomic system–meso-market–micro-behavior” based on multi-source data from 2020 to 2024. It empirically explores the formation mechanism of intergenerational differences in impulse buying. The results show that the behavior differences of different groups are significantly driven by income gradient, cross-border policies (tariff adjustment and consumer protection regulations), and collectivism/individualism cultural orientations. The innovative contribution of this study is reflected in three aspects: Firstly, it breaks through the limitation of a single discipline, and for the first time, it incorporates structural variables such as policy synergy effect and family structure change into the theoretical framework of impulse buying, quantifying and revealing the differentiated impact of institutional heterogeneity in ASEAN markets on intergenerational behavior. Secondly, it reconstructs the transmission path of “cultural values–family structure–intergenerational behavior” and finds that the inhibitory effect of collectivism on impulse buying tends to weaken with age. Thirdly, it proposes a “policy instrument–generational response” matching model and verifies the heterogeneous impact of the same policy (such as tariff reduction) on different generations. This study fills the gaps in related research and can provide empirical support for ASEAN enterprises to formulate stratified marketing strategies and for policymakers to optimize cross-border e-commerce regulation. which is of great significance to promote the sustainable development of the regional live-broadcast e-commerce ecology. Full article