Search Results (670)

Tau protein misfolding and aggregation are central to Tauopathies, yet the temporal dynamics of Tau interactions in vivo remain poorly understood. Here, we applied quantitative proteomics to demonstrate that the interactome of human Tau in adult Drosophila brains changes dynamically over a 12-day time course, revealing a progressive shift from early cytosolic and ribosomal associations to late enrichment of mitochondrial and synaptic partners. Notably, the mitochondrial pore protein Porin/VDAC1 was identified as a late-stage interactor and functional analyses demonstrated that Tau overexpression impairs mitochondrial respiration, elevates oxidative damage, and disrupts carbohydrate homeostasis. To validate this temporally specific interaction, Porin was downregulated, resulting in reduced Tau mitochondrial association, phosphorylation and aggregation. Paradoxically, however, Porin attenuation exacerbated Tau-induced toxicity, including shortened lifespan, locomotor deficits, and impaired learning. These findings indicate that while Porin facilitates pathological Tau modifications, it is also essential for neuronal resilience, highlighting a complex role in modulating Tau toxicity. Our study provides a temporal map of Tau-associated proteome changes in vivo and identifies mitochondria as critical mediators of Tau-driven neurodegeneration. Full article

Sirtuins (SIRT1–SIRT7) are NAD⁺-dependent deacetylases that link cellular energy status to chromatin maintenance, mitochondrial function and inflammatory signaling. While modulation of SIRT1, SIRT3 and SIRT6 extends lifespan in model organisms, evidence in extreme-age humans is scarce. We quantified protein and mRNA levels, and protein-to-mRNA ratios for SIRT1, SIRT3 and SIRT6 in buccal epithelial cells obtained from healthy young adults, middle/late-aged individuals and nonagenarians/centenarians residing in a longevity-enriched region of south-eastern Azerbaijan. The cohort comprised 23 participants, stratified by sex and cardiovascular disease (CVD) status (5 per sex/CVD subgroup). This design allows us to: (1) define a baseline “sirtuin profile” of healthy longevity, (2) evaluate the impact of CVD as a prevalent age-related pathology, and (3) explore potential sex-specific modulation. These findings establish an initial human framework linking sirtuin translational control to healthy ageing and cardiovascular health. Full article

Caenorhabditis elegans is one of the most extensively studied model organisms in biology. Its advantageous features, including genetic homology with humans, conservation of disease pathways, transparency, short lifespan, small size and ease of maintenance have established it as a powerful system for research in aging, genetics, molecular biology, disease modeling and drug discovery. However, traditional methods for worm handling, culturing, scoring and imaging are labor-intensive, low throughput, time consuming, susceptible to operator variability and environmental influences. Addressing these challenges, recent years have seen rapid innovation spanning microfluidics, robotics, imaging platforms and AI-driven analysis in C. elegans-based research. Advances include micromanipulation devices, robotic microinjection systems, automated worm assays and high-throughput screening platforms. In this review, we first summarize foundational developments prior to 2020 that shaped the field, then highlight breakthroughs from the past five years that address key limitations in throughput, reproducibility and scalability. Finally, we discuss ongoing challenges and future directions for integrating these technologies into next-generation automated C. elegans research. Full article

Background: There is an emerging need for new scalable behavioral assays, i.e., assays that are feasible to administer from the comfort of the person’s home, with ease and at higher frequency than clinical visits or visits to laboratory settings can afford us today. This need poses several challenges which we address in this work along with scalable solutions for behavioral data acquisition and analyses aimed at diversifying various populations under study here and to encourage citizen-driven participatory models of research and clinical practices. Methods: Our methods are centered on the biophysical fluctuations unique to the person and on the characterization of behavioral states using standardized biorhythmic time series data (from kinematic, electrocardiographic, voice, and video-based tools) in naturalistic settings, outside a laboratory environment. The methods are illustrated with three representative studies (58 participants, 8–70 years old, 34 males, 24 females). Data is presented across the nervous systems under a proposed functional taxonomy that permits data organization according to nervous systems’ maturation and decline levels. These methods can be applied to various research programs ranging from clinical trials at home, to remote pedagogical settings. They are aimed at creating new standardized biometric scales to screen and diagnose neurological disorders across the human lifespan. Results: Using this remote data collection system under our new unifying statistical platform for individualized behavioral analysis, we characterize the digital ranges of biophysical signals of neurotypical participants and report departure from normative ranges in neurodevelopmental and neurodegenerative disorders. Each study provides parameter spaces with self-emerging clusters whereby data points corresponding to a cluster are probability distribution parameters automatically classifying participants into different continuous Gamma probability distribution families. Non-parametric analysis reveals significant differences in distributions’ shape and scale (p < 0.01). Data reduction is realizable from full probability distribution families to a single parameter, the Gamma scale, amenable to represent each participant within each subclass, and each cluster of similar participants within each cohort. We report on data integration from stochastic analyses that serve to differentiate participants and propose new ways to highly scale our research, education, and clinical practices. Conclusions: This work highlights important methodological and analytical techniques for developing personalized and scalable biometrics across various populations outside a laboratory setting. Full article

Aging is characterized by a progressive decline in physiological function that impairs performance and increases vulnerability to disease and mortality. Delaying this deterioration is key to promoting healthy aging. Age-associated functional decline is closely linked to alterations in intermediary metabolism, including disrupted lipid metabolism and impaired mitochondrial function. Counteracting these metabolic changes, particularly those affecting basal metabolic rate and energy utilization, may be a feasible strategy to extend healthspan. The Renin-Angiotensin System (RAS), which controls blood pressure through Angiotensin II, an octapeptide hormone generated from Angiotensin I by Angiotensin-Converting Enzyme (ACE), has been identified as a potential target for aging therapies. ACE inhibitors, such as the commonly prescribed vasodilator lisinopril, have been shown to exert beneficial effects on healthspan. Disentangling their systemic effects from direct cellular actions on intermediary metabolism is challenging in humans but can be pursued in model organisms. Drosophila melanogaster expresses two ortholog of mammalian ACE, Ance and Acer, which have diverged to acquire different functions. Since fundamental cellular processes are evolutionarily conserved and flies have an open circulatory system, Drosophila provides a versatile model for translational studies on ACE inhibition and aging. Recent studies in Drosophila reveal sex-, age-, and genetic background-specific effects of lisinopril on metabolic rates and aging-related organismal phenotypes. Integrating preclinical findings from Drosophila with clinical studies will be essential to define the therapeutic potential of RAS inhibition in extending lifespan and delaying aging. Full article

Background: Engineered nanoparticles (NPs)—titanium dioxide, silver, zinc oxide and silica—are widely used in cosmetics for UV protection, antimicrobial activity and texturising effects. Chronic consumer-level exposure may impair skin-barrier integrity, disturb microbiome composition and dysregulate immune signalling via the gut–skin axis. Current regulatory frameworks typically omit chronic- or microbiome-focused safety assessments, leaving potential gaps. Objectives: This study aimed to evaluate the long-term effects of cosmetic-relevant NPs (titanium dioxide, silver, zinc oxide, silica) on skin and gut microbiota, epithelial-barrier integrity and immune signalling—including telocyte- and exosome-mediated pathways—and to identify regulatory shortcomings, particularly the absence of microbiome endpoints, validated chronic models and consideration of vulnerable populations. Methods: Following PRISMA 2020, PubMed, Scopus and Web of Science were searched for English-language in vivo animal or human studies (December 2014–April 2025) meeting chronic-exposure criteria (≥90 days in rodents or >10% of lifespan in other species; for humans, prolonged, repetitive application over months to years consistent with cosmetic use). Although not registered in PROSPERO, the review adhered to a pre-specified protocol. Two independent reviewers screened studies; risk of bias was assessed using a modified SYRCLE tool (animal) or adapted NIH guidance (zebrafish). Owing to heterogeneity, findings were synthesised narratively. Results: Of 600 records, 450 unique articles were screened, 50 full texts were assessed and 12 studies were included. Oral exposure predominated and was associated with dysbiosis, barrier impairment, immune modulation and metabolic effects. Dermal models showed outcomes from minimal change to pronounced immune activation, contingent on host susceptibility. Comparative human–animal findings are summarised; telocyte and exosome pathways were largely unexplored. Regulatory reviews (EU SCCS, US FDA and selected Asian frameworks) revealed no requirements for chronic microbiome endpoints. Limitations: Evidence is limited by the small number of eligible studies, heterogeneity in NP characteristics and exposure routes, predominance of animal models and a scarcity of longitudinal human data. Conclusions: Cosmetic nanoparticles may disrupt the microbiome, compromise barrier integrity and trigger immune dysregulation—risks amplified in vulnerable users. Existing regulations lack requirements for chronic exposure, microbiome endpoints and testing in vulnerable groups, and neglect mechanistic pathways involving telocytes and exosomes. Long-term, real-world exposure studies integrating gut–skin microbiome and immune outcomes, and harmonised global nanomaterial-safety standards, are needed to ensure safer cosmetic innovation. Full article

Electronic waste is becoming a growing global pollution issue due to short device lifespans and insufficient safe disposal methods. Hazardous metals like arsenic and mercury from electronic waste harm both the environment and human health. Recycling processes remain underdeveloped, requiring new eco-friendly solutions. This paper reports on the synthesis and properties of the cationic surfactants ammonium terthiophene (CTT) and 3,4-propylene-dioxythiophene (C-ProDOT), which may have potential use in organic electronics. Ecotoxicological tests showed no significant long-term toxicity and medium-to-high biodegradability, which are keys for environmental protection. These surfactants also displayed selective bacterial adhesion, making them candidates for bionic devices. Life cycle assessment revealed higher energy use and ecotoxicity for C-ProDOT than CTT, underscoring the need for sustainable chemical design. Full article

Sugar and sucralose are frequently used together and separately in human food and beverages, which is the reason why studying their biological action on different organisms is really important. Nevertheless, the effect of highly concentrated sugar diet on male infertility is still under evaluation. The most important is that biological activity of sucralose, a chloroorganic synthetic sweetener, is highly persistent and difficultly altered in the environment, as its influence on the biological activity of other substances has not been completely elucidated yet. For this reason, in this work, sugar and sucralose–sugar mixtures, frequently used in beverages and other food products, influence Drosophila melanogaster behavior, longevity, reproductive performance, and genomic integrity is investigated. It has been demonstrated that an increase in sugar concentration promotes biological viability by enhancing prolificacy, lifespan, and locomotor performance. However, this only occurs up to a certain threshold concentration; beyond this, metabolic imbalance occurs. The presence of sucralose in solutions further augments the toxic effect, indicating high genotoxicity of the sweetener at doses over 0.5%, leading to significant DNA alterations and changing the Drosophila melanogaster behavior pattern. Therefore, either sugar or sucralose metabolic impact and toxicity is dose-related and their common presence in the solution might lead to the synergetic effect. Full article

Aging is a complex biological process influenced by internal and external factors, with diet and gut microbiota emerging as pivotal, interconnected modulators. This review explores their triangular relationship, emphasizing how they dynamically interact to shape health across the lifespan. Aging involves notable shifts in gut microbiota, including reduced diversity, increased pro-inflammatory taxa, and impaired production of key metabolites, like short-chain fatty acids. These changes contribute to systemic inflammation, immune-senescence, and age-related conditions, such as cognitive decline and metabolic disorders. Diet, particularly Mediterranean and plant-based patterns, plays a critical role in modulating gut microbiota by enhancing beneficial microbes and their metabolic functions. In contrast, Western-style diets rich in saturated fats and processed foods promote dysbiosis and accelerate aging. The review synthesizes evidence from human studies, animal models, and interventions to show how microbiota mediates diet-driven effects on aging. It also explores the role of specific nutrients, fiber, omega-3 fatty acids, and polyphenols in influencing microbial and host aging biology. Emerging therapies, including probiotics, prebiotics, and precision nutrition, show promise for promoting healthy aging by restoring microbial balance. However, gaps remain, including the need for long-term, age-specific studies, standardized microbiome protocols, and integrated omics approaches to support targeted longevity strategies. Full article

Neurodegenerative diseases are characterized by the irreversible and progressive loss of nerve cell function, leading to gradual cognitive decline. These diseases often result in a deterioration in quality of life and a shortened lifespan. The most common neurodegenerative diseases in humans are Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis. The recent growing interest is due to the increasing incidence of these diseases and the lack of effective therapeutic methods that could prevent them. However, bioactive compounds contained in foods and beverages have been found to play a significant role in this respect. In particular, a growing body of reports suggests the inverse relationship between wine consumption and the development of such diseases. The main components of wine include ethyl alcohol and polyphenolic compounds (obviously, on a different scale). Wine polyphenols exhibit antioxidant and anti-inflammatory effects. Some of them may cross the blood–brain barrier and then affect the functioning of neurons and other cells. Such activity is considered to be an important factor in the prevention of neurodegenerative diseases related to inflammation, oxidative stress, and mitochondrial dysfunctions. The review presents the current knowledge on the impact of wine consumption and its components on the development of neurodegenerative diseases. Full article

As the region with the earliest housing stock market and the most advanced development in China, the Pearl River Delta has experienced extensive housing demolition and construction, leading to buildings having short lifespans. The environmental pollution generated during this process has brought attention to the concept of green buildings. However, whether due to previous patterns of demolition and construction or the significant impacts of social and economic changes in the current and future housing stock contexts, the comprehensive adaptability of human-centered living spaces remains a crucial issue. This focus is strongly related to the residents’ psychological responses, such as sense of belonging, safety, and atmosphere, across different scales of physical environment. However, most housing evaluation systems regarding sustainable issues are green building evaluation systems. And their concept and practice are often accompanied by a neglect of the interrelationship between people and the built environment, as well as a lack of an appropriate methodological framework to integrate these elements in the temporal dimension. This paper primarily tries to provide new answers to old questions about housing durability by reconceptualizing evaluation systems beyond ecological metrics, while simultaneously challenging accepted answers that privilege material and energy indicators over sociocultural embeddedness. Moreover, an effective housing evaluation framework must transcend purely technical or ecological indicators to systematically integrate the temporal and sociocultural factors that sustain long-term residential quality, particularly in rapidly transforming urban contexts. Therefore, theories closely related to building longevity, such as open building and the “level” strategy, were introduced. Based on this combined methodological framework, selected cases of local traditional housing and green building evaluation systems were studied, aiming to identify valuable longevity factors and improved evaluation methods. Furthermore, two rounds of expert consultation and a data analysis were conducted. The first round helped determine the local indexes and preliminary evaluation methods, while the second round helped confirm the weighting value of each index through a questionnaire study and data analysis. This systematic study ultimately established a preliminary long-term housing evaluation system for the Pearl River Delta. Full article

Background/Objectives: Cervical cancer (CC), a highly prevalent female neoplasia, has been prevented through repeated cervicovaginal cytology, the so-called Pap test, across women’s lifespans. The now undebatable role of Human Papillomaviruses in the etiology of CC and the development of high-throughput automated molecular amplification diagnostic platforms is allowing for the replacement of the Pap test with HPV testing. The objective of this review is to contextualize the current strategies for cervical cancer screening using molecular assays. Methods: The many existing screening tools relying on molecular markers and their advantages and drawbacks are discussed. Results: Testing for oncogenic Human Papillomavirus DNA is presently the mainstay strategy for molecular screening, replacing cervicovaginal cytology. Conclusions: The presence of HPV-DNA is the most sensitive marker for cervical cancer and its precursor lesions. However, its adoption has led to an increase in the number of screening-positive subjects, generating extra demand for triage resources. New algorithms and technologies are fast being developed to address this need, moving toward risk-based management. Full article

Potential climatic and land-use changes may favor an increase in the population densities and range expansion of oak processionary moth (OPM) in Central and Western Europe in the future. This could lead to more significant threats to human and animal health, caused by the urticating setae released by OPM larvae, and more severe oak defoliation by the larvae. To cope with the public health issue, a basis for OPM hazard assessment and management was created by quantifying the setae formation potential of OPM. While a single larva forms ca. 857,000 setae during its lifespan, a single infested oak tree may be contaminated with up to 10–24 billion (10⁹) setae during an OPM outbreak. Moreover, the possible setae contamination threat to humans through airborne setae dispersal was studied in worst-case exposure simulations in the field. The highest airborne setae concentration was straight downwind, but turbulences up to 150° from the air flow were observed. The findings of this study will improve biohazard quantification as a basis for decision-making on preventive or mechanical control measures and enable an effective protection of human health. This study provides applicable information to derive warnings and recommendations for the public, as well as land managers and authorities. Full article

Predictive maintenance is a crucial component of smart manufacturing in Industry 4.0, utilizing data from IoT sensor networks and machine learning algorithms to predict equipment failures before they happen. This proactive approach enables timely maintenance of equipment and machinery, reducing unplanned downtime, extending equipment lifespan, and enhancing overall system reliability, ultimately leading to more efficient and cost-effective operations. Conventional machinery and equipment maintenance approaches often rely on periodic manual inspections, human observations, and monitoring, which can be time-consuming, inefficient, and resource-intensive. Therefore, implementing automation through predictive models based on IoT and machine learning techniques is crucial for optimizing the maintenance of machinery and equipment. This paper aims to leverage machine learning techniques to develop predictive maintenance models, including electric motor temperature and vibration prediction, using data from established sensor networks and production data from ERP systems. The models are designed to predict potential issues within the next ten minutes, such as whether temperature or vibration levels will exceed predefined thresholds. Full article

Oviduct epithelial cells (OECs) constitute a critical component of the oviductal mucosa, providing essential microenvironmental support for fertilization and early embryonic development. Their frequent application in embryo co-culture systems is constrained in yaks (Bos grunniens) by limited tissue availability and the short lifespan of primary yak oviduct epithelial cells (YOECs). To address this limitation, we established immortalized YOEC lines using a lentiviral vector system. Primary YOECs isolated from reproductive tract tissues of adult female yaks via enzymatic digestion were immortalized through individual and combined transfection with simian virus 40 large T antigen (SV40LT) and human telomerase reverse transcriptase (hTERT). The resulting immortalized lines (YOECs-S: SV40LT alone; YOECs-HS: dual SV40LT/hTERT) kept their typical cobblestone shape and still made cytokeratin 18. Both lines exhibited stable SV40LT and hTERT expression (p > 50), maintained diploid karyotypes, and demonstrated serum-dependent growth, contact inhibition, and hormone responsiveness. Notably, YOECs-HS displayed superior proliferative capacity and phenotypic stability during long-term culture. This study reports the first successful establishment and comprehensive characterization of immortalized YOEC lines. These validated models provide a valuable experimental platform for optimizing yak embryo–oviduct epithelial cell co-culture systems and advancing reproductive research in this high-altitude-adapted species. Full article