Search Results (2,805)

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

Background: Autism spectrum disorder (ASD) represents a neurobiological disorder with a high prevalence in the children’s population. The aim of the present review was to assess the current evidence on the use of salivary biomarkers for the early diagnosis of ASD. Materials and methods: A search was conducted on the electronic databases PUBMED/Medline, Google Scholar and Scopus for the retrieval of articles concerning the study topic. Results: A total of 22 studies have been included in the present review considering 21 articles identified from databases and 1 article included using a manual search. A wide range of biomarkers have been proposed for early detection of ASD diseases including nonspecific inflammation markers like interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), oxidative stress markers like superoxide dismutase and glutathione peroxidase, hormones such as cortisol and oxytocin, various microRNAs including miR-21, miR-132 and miR-137, and exosomes. The techniques used for biomarke detection may vary according to molecule type and concentration. Conclusions: salivary biomarkers could represent a potential useful tool for the primary detection of several systemic diseases including ASD, taking advantage of non-invasiveness and cost-effective capability compared to other biofluid-based diagnostic techniques. Full article

Varicocele is a common, potentially correctable condition associated with impaired male fertility. Despite being frequently encountered in clinical andrology, its pathophysiological mechanisms, diagnostic criteria, and therapeutic approaches remain areas of active investigation and debate. The authors conducted a comprehensive literature search, using the PubMed database, covering clinical studies, systematic reviews, meta-analyses, and current international guidelines from the past ten years. Emphasis was placed on studies investigating novel diagnostic modalities, therapeutic innovations, and prognostic markers. Emerging evidence supports the multifactorial pathophysiology of varicocele, involving oxidative stress, hypoxia, inflammatory pathways, and potential genetic predisposition. Biomarkers, including microRNAs, antisperm antibodies, and sperm DNA fragmentation, offer diagnostic and prognostic utility, though their routine clinical implementation requires further validation. Advances in imaging, such as shear wave elastography, may improve diagnostic accuracy. While microsurgical subinguinal varicocelectomy remains the gold standard, technological refinements and non-surgical alternatives are being explored. Indications for treatment have expanded to include selected cases of non-obstructive azoospermia, hypogonadism, and optimization for assisted reproduction, though high-level evidence is limited. Full article

Thermoplastic polyurethane (TPU) electrospun fiber membranes possess unique micro-nano structures and excellent properties. Adjusting their wettability enables the directional transportation of lubricants. A conventional method for adjusting porosity and wettability involves inducing membrane shrinkage using absolute ethanol and heat treatment. However, the shrinkage response and the corresponding changes in the tensile properties of TPU fiber membranes after induction remain unclear, limiting their applications. Thus, in this study, after being peeled off, the samples were first left to stand at room temperature (RT) for 24 h to release residual stress and stabilize their dimensions, and then treated with dehydrated ethanol at RT and high temperature, respectively, with their shrinkage behaviors observed and recorded. The results showed that TPU nanofiber membranes shrank significantly in absolute ethanol, and the degree of shrinkage was temperature-dependent. The shrinkage rates were 2% and 4% in dehydrated ethanol at room temperature and high temperature, respectively, and heating increased the shrinkage effect by 200%. These findings prove that absolute ethanol causes TPU fibers to shrink, and high temperatures further promote shrinkage. However, although the strong synergistic effect of heat and solvent accelerates shrinkage, it may induce internal structural defects, resulting in the deterioration of mechanical properties. The contraction response induced by anhydrous ethanol stimulation can be used to directionally adjust the local density and modulus of TPU nanofiber membranes, thereby changing the wettability. This approach provides new opportunities for applications in areas such as medium transportation and interface friction reduction in lubrication systems. Full article

The cement sheath is critical for ensuring the long-term safety and operational efficiency of oil and gas wells. However, complex geological conditions and operational stresses during production can induce cement sheath deterioration and cracking, leading to reduced zonal isolation, diminished hydrocarbon recovery, and elevated operational expenditures. This study investigates the development of a novel microbial self-healing well cement slurry system, employing fly ash as microbial carriers and sustained-release microcapsules encapsulating calcium sources and nutrients. Systematic evaluations were conducted, encompassing microbial viability, cement slurry rheology, fluid loss control, anti-channeling capability, and the mechanical strength, permeability, and microstructural characteristics of set cement stones. Results demonstrated that fly ash outperformed blast furnace slag and nano-silica as a carrier, exhibiting superior microbial loading capacity and viability. Optimal performance was observed with additions of 3% microorganisms and 3% microcapsules to the cement slurry. Microscopic analysis further revealed effective calcium carbonate precipitation within and around micro-pores, indicating a self-healing mechanism. These findings highlight the significant potential of the proposed system to enhance cement sheath integrity through localized self-healing, offering valuable insights for the development of advanced, durable well-cementing materials tailored for challenging downhole environments. Full article

This study investigates the improvement effect and micro-mechanism of guar gum and palm fibers, two eco-friendly materials, on expansive soil. The study uses disintegration tests, unconfined compressive strength tests, triaxial compression tests, and SEM analysis to evaluate the enhancement of mechanical properties. The results show that the guar gum–palm fiber composite significantly improves the compressive and shear strength of expansive soil. The optimal ratio is 2% guar gum, 0.4% palm fiber, and 6 mm palm fiber length. Increasing fiber length initially boosts and then reduces unconfined compressive strength. Guar gum increases unconfined compressive strength by 187.18%, further improved by 20.9% with palm fibers. When fiber length is fixed, increasing palm fiber content increases and then stabilizes peak stress and shear strength (cohesion and internal friction angle), improving by 27.30%, 52.1%, and 12.4%, respectively, compared to soil improved with only guar gum. Micro-analysis reveals that guar gum enhances bonding between soil particles via a gel matrix, improving water stability and mechanical properties, while palm fibers reinforce the soil and inhibit crack propagation. The synergistic effect significantly enhances composite-improved soil performance, offering economic and environmental benefits, and provides insights for expansive soil engineering management. Full article

MicroRNA528 (miR528) is a microRNA found only in monocotyledonous (monocot) plants. It has been widely reported that miR528 is involved in the regulation of plant growth and development, such as flowering, architecture, and seed and embryogenic development, in addition to playing a crucial role in response to various biotic and abiotic stresses, such as plant pathogens, salt stress, heat/cold stress, water stress, arsenic stress, oxidative stress, heavy-metal stress, and nutrient stress. Given that it is specific to monocot plants, to which the major staple food crops such as rice and wheat belong, a review of studies investigating its diverse functional roles and underlying mechanisms is presented. This review focuses on the processes in which miR528 and its targets are involved and examines their regulatory relationships with significant participation in plant development and stress responses. It is anticipated that more biological functions and evolutionary effects of miRNA targets will be elucidated with the increase in knowledge of miRNA evolution and examination of target mRNAs. Full article

While the explosive growth in e-commerce stresses urban logistics systems, city planners lack of fine-grained data in order to anticipate and manage the resulting freight flows. Using a three-stage analytical approach combining descriptive zonal statistics, hotspot analysis and different regression modeling from univariate to geographically weighted regression, this study integrates one year of parcel deliveries from a leading courier with open spatial layers of land-use zoning, census population, mobile-signal activity and household income to model last-mile demand across different land use types. A baseline linear regression shows that residential population alone accounts for roughly 30% of the variance in annual parcel volumes (2.5–3.0 deliveries per resident) while adding daytime workforce and income increases the prediction accuracy to 39%. In a similar approach where coefficients vary geographically with Geographically Weighted Regression to capture the local heterogeneity achieves a significant raise of the overall R² to 0.54 and surpassing 0.70 in residential and institutional districts. Hot-spot analysis reveals a highly fragmented pattern where fewer than 5% of blocks generate more than 8.5% of all deliveries with no apparent correlation to the broaden land-use classes. Commercial and administrative areas exhibit the greatest intensity (1149 deliveries per ha) yet remain the hardest to explain (global R² = 0.21) underscoring the importance of additional variables such as retail mix, street-network design and tourism flows. Through this approach, the calibrated models can be used to predict city-wide last-mile demand using only public inputs and offers a transferable, privacy-preserving template for evidence-based freight planning. By pinpointing the location and the land uses where demand concentrates, it supports targeted interventions such as micro-depots, locker allocation and dynamic curb-space management towards more sustainable and resilient urban-logistics networks. Full article

The ratchet click mechanism in mechanical watch movements is a micro-component essential to prevent the unwinding of the caliber mainspring, providing secure energy storage during recharging. Despite its geometrical simplicity, the ratchet click undergoes to a complex distribution of stress, elevated strains, and cyclical mechanical deformations, affecting its long-term reliability. Despite being a crucial element in all mechanical watch movements, the non-return system appears to have been overlooked in scientific literature, with no studies available on its design, modeling, and micromachining. In this work, we introduce a novel Finite Element Method (FEM) -based design strategy for the ratchet click, systematically refining its geometry and dimensional parameters to minimize peak stress and improve durability. A mechanical simulation model was created to simulate the boundary conditions, contact interactions, and stress distributions on the part. If compared with the standard component, the optimized design exhibits a decrease in peak stress values. The mechanism was micro-machined, and it was experimentally tested to validate the numerical model outputs. The integrated digital–physical approach not only underscores the scientific contribution of coupling advanced simulation with experimental validation of complex micromechanisms but also provides a generalizable method for enhancing performance of micro-mechanical components while preserving their historical design heritage. Full article

Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes. Full article

Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders. Full article

Mycotoxins represent a group of highly toxic secondary metabolites produced by diverse fungal pathogens. Mycotoxin contaminations frequently occur in foods and feed and pose significant risks to human and animal health due to their carcinogenic, mutagenic, and immunosuppressive properties. Notably, deoxynivalenol, zearalenone, fumonisins (mainly including fumonisins B1, B2, and FB3), aflatoxin B1 (AFB1), and T-2/HT-2 toxins are the major mycotoxin contaminants in foods and feed. Undoubtedly, exposure to these mycotoxins can disrupt gut health, particularly damaging the intestinal epithelium in humans and animals. In this review, we summarized the detrimental effects caused by these mycotoxins on the intestinal health of humans and animals. The fundamental molecular mechanisms, which cover the induction of inflammatory reaction and immune dysfunction, the breakdown of the intestinal barrier, the triggering of oxidative stress, and the intestinal microbiota imbalance, were explored. These signaling pathways, such as MAPK, Akt/mTOR, TNF, TGF-β, Wnt/β-catenin, PKA, NF-kB, NLRP3, AHR, TLR2, TLR4, IRE1/XBP1, Nrf2, and MLCK pathways, are implicated. The abnormal expression of micro-RNA also plays a critical role. Finally, we anticipate that this review can offer new perspectives and theoretical foundations for controlling intestinal health issues caused by mycotoxin contamination and promote the development of prevention and control products. Full article

Plastic pollution has recently become a serious environmental problem, since the continuous increase in plastic production and use has generated enormous amounts of plastic waste that decomposes to form micro- and nanoparticles (MPs/NPs). Recent evidence suggests that nanoplastics may be potent toxins because they are able to freely cross biological barriers, posing health risks, particularly to developing organisms. Therefore, the aim of the current study was to investigate the toxic potential of polystyrene nanoparticles (PS-NPs) on the jejunum of immature rats. Two-week-old animals were orally exposed to environmentally relevant dose of small PS-NPs (1 mg/kg b.w.; 25 nm) for 3 weeks. We detected a significant accumulation of PS-NPs in the epithelium and subepithelial layer of the intestine, which resulted in significant changes in the expression of genes related to gut barrier integrity, nutrient absorption, and endocrine function. Moreover, increased expression of proinflammatory cytokines was observed together with decreased antioxidant capacity and increased markers of oxidative damage to proteins. Additionally, in the jejunal extracts of exposed rats, we also noted changes in the metabolite profile, mainly amino acids involved in molecular pathways related to cellular energy, inflammation, the intestinal barrier, and protein synthesis, which were consistent with the observed molecular markers of inflammation and oxidative stress. Taken together, the results of the metabolomic, molecular, and biochemical analyses indicate that prolonged exposure to PS-NPs may disrupt the proper function of the intestine of developing organisms. Full article

Plants are constantly exposed to environmental stressors such as drought, salinity, and extreme temperatures, which threaten their growth and productivity. To counter these challenges, they employ complex molecular defense systems, including epigenetic modifications that regulate gene expression without altering the underlying DNA sequence. This review comprehensively examines the emerging roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as central signaling molecules orchestrating epigenetic changes in response to abiotic stress. In addition, biotic factors such as pathogen infection and microbial interactions are considered for their ability to trigger ROS/RNS generation and epigenetic remodeling. It explores how ROS and RNS influence DNA methylation, histone modifications, and small RNA pathways, thereby modulating chromatin structure and stress-responsive gene expression. Mechanistic insights into redox-mediated regulation of DNA methyltransferases, histone acetyltransferases, and microRNA expression are discussed in the context of plant stress resilience. The review also highlights cutting-edge epigenomic technologies such as whole-genome bisulfite sequencing (WGBS), chromatin immunoprecipitation sequencing (ChIP-seq), and small RNA sequencing, which are enabling precise mapping of stress-induced epigenetic landscapes. By integrating redox biology with epigenetics, this work provides a novel framework for engineering climate-resilient crops through the targeted manipulation of stress-responsive epigenomic signatures. Full article

Replicative or stress-induced senescence disrupts the functioning of multipotent mesenchymal stromal cells (MSCs) required for tissue renewal and regeneration. Aged MSCs demonstrate reduced proliferation, impaired differentiation, and aberrant secretory activity, defined as “senescence-associated secretory phenotype” (SASP). SASP is characterized by elevated secretion of proinflammatory cytokines and specific extracellular vesicles (SASP-EVs), which affect the cellular microenvironment and promote tissue dysfunction. However, molecular mechanisms responsible for senescent phenotype propagation remain largely obscure. Earlier, we demonstrated suppression of adipogenic differentiation and insulin sensitivity of young MSCs by SASP-EVs. In this study, we elucidated potential mechanisms underlying SASP-EVs’ effects on MSCs. Bioinformatic analysis revealed that insulin signaling components are the most probable targets of SASP-EVs microRNA cargo. We demonstrated that SASP-EVs downregulated intracellular AGO1 levels, but surprisingly, PTEN levels were upregulated. Specifically, the increase in PTEN content was provided by its nuclear fraction. We have found that the intracellular PTEN distribution in young MSCs treated by SASP-EVs was similar to senescent MSCs. Furthermore, PTEN upregulation was accompanied by increased PTENP1 expression—a molecular sponge for PTEN-targeting microRNAs. Our findings indicate that nuclear PTEN could be a hallmark of senescent MSCs, and SASP-EVs propagate the senescent phenotype in young MSCs by promoting PTEN nuclear localization. Full article