: Schizophrenia and schizoaffective disorder are generally treated with second-generation antipsychotic drugs. These drugs are mostly D2 and 5-HT2A antagonists. They improve positive schizophrenia symptoms sufficiently well; however, they ameliorate negative schizophrenia symptoms and cognitive functions to a small extent. We review novel antipsychotic drugs exerting a partial agonism at dopaminergic and serotonergic receptors such as cariprazine, brexipiprazole and lumateperone. Besides, the mechanisms of actions of non-anti-dopaminergic antipsychotic drugs are pointed out. Updated neural networks are used to explain the mechanism of action of M4 and M1 receptor agonists, for example xanomeline combined with trospium or emraclidine, and trace-amine-associated receptor 1 agonists (TAAR1), for example ulataront. Phase 3 clinical trials of new third generation antipsychotic drugs are presented. Novel antipsychotic drugs with a partial agonism at D2 and D3 receptors improve positive and negative schizophrenia symptoms as well as cognitive symptoms better than second generation antipsychotic drugs. Besides, they are well tolerated. M4 and M1 receptor agonists, i.e. xanomeline combined with trospium or emraclidine, and TAAR1 agonists, i.e. ulataront, have promising results in clinical trials; they well improve negative schizophrenia symptoms and cognitive functions. Phase 3 clinical trials offer promising results for anti-dopaminergic and non-anti-dopaminergic novel antipsychotic drugs. These new non-anti-dopaminergic antipsychotic drugs better emend negative schizophrenia symptoms, and they better improve cognitive functions than second-generation antipsychotic drugs. Promising new antipsychotic drugs are cariprazine, brexipiprazole, lumateperone, ulataront, and xanomeline combined with trospium. Although phase 3 clinical studies are not yet completed, they showed a therapeutic effect superior to those achieved by second-generation antipsychotic drugs. They are tolerated very well, and they better treat negative schizophrenia symptoms and improve cognitive functions.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

The aging ability of dry white wines has been increasingly recognised. The present work aimed to understand which sensory factors drive their quality evaluation by experienced tasters. Individuals assessed several aesthetic, synthetic, and analytic flavour attributes, using dark tasting glasses. Wines originated from the grape varieties Alvarinho, Arinto, Sauvignon Blanc and Pinot Bianco with a wide range of ages. Basic physical-chemical analysis, browning (Abs 420 nm), elemental composition and a partial volatile fraction were also determined. The overall quality scores were a function of complexity and balance and were negatively influenced by the perception of faultiness. The different ages could be associated with a continuous sensory space characterised by a decreasing perception of freshness and an increase in the mellowed flavours. All wines shared an austere in-mouth perception elicited by their acidity, saltiness, bitterness, smoothness and dryness. Nevertheless, quality scores were similar from the youngest to the oldest-tasted wines (17 years old). The exception was a Sauvignon Blanc wine from a recent vintage that was judged as faulty due to the perception of earthiness. Overall, the tasted wines displayed an unexpected aging ability as demonstrated by the difference between the predicted and real wine ages. To improve the recognition of old wines, the metaphor “mellowed by age” is proposed to describe flavours resulting from beneficial aging instead of “oxidised by age”.

Aging causes various degenerative diseases in the older adult population. Senescence, a state of permanent cell-cycle arrest accompanied by the production of various pro-inflammatory factors known as senescence-associated secretory phenotype (SASP), is considered a significant contributor to the aging process and its chronic diseases. Ample evidence showed that various stressors could induce senescence, including DNA damage, telomere shortening and damage, activation of oncogenes, and mitochondrial dysfunction. Numerous credible findings indicate that environmental agents can induce senescence, including UV radiation, a high-fat diet, heavy metal exposure, and cigarette smoke. These findings posed the possibility that many more environmental agents may induce senescence and accelerate aging but remain unidentified. Senescence also becomes more intriguing due to its promising future as a pharmacological target to blunt the detrimental effects of aging and prevent aging-related diseases, either by eliminating the senescent cells or by controlling the SASP. On the other hand, investigating senescence has become more intricate due to the need for a multi-marker approach and translation in vivo analysis. This review will discuss senescence and its biomarkers, how to identify gerontogens in vivo, and also the development of senotherapy that targets senescent cells.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

Background: Retinal hemorrhages are an important ophthalmic diagnostic sign of underlying systemic vascular disorder. Capsaicin is a bioactive component of chili peppers used in most countries. Capsaicin crosses the blood–brain barrier in an efficient manner. Human exposure to capsaicinoids through diet is frequent and often substantial. Presumed lack of capsaicin toxicity in diet does not preclude rare adverse effects related to actions on the central neural system. Particularly on the retina, due to the reasons outlined in this case report. Methods: A case of a 34-year-old man, who reported sudden blurring of vision and micropsia in his left eye following ingestion of a considerable amount of red pepper. Results: The case study suggests that acute or chronic consumption of substantial amounts of hot red pepper in individuals with high reactivity towards TRPV1 agonists and/or higher expression of TRPV1 receptors in retinal ganglion cells causes retinal neovascularization. Conclusion: Acute consumption of red pepper may harm vision. This hypothesis can be easily evaluated retrospectively in larger sets of data.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

As recently as 2002 programmed aging in mammals was widely thought to be theoretically impossible based on generally accepted concepts regarding the evolution process. However, as described in this article, genetics discoveries, results of selective breeding, and other direct evidence strongly support the idea that aging creates an evolutionary advantage and that therefore complex biological mechanisms evolved that control mammal aging. Like similar life-cycle programs that control reproduction, growth, and menopause the aging program can adjust the aging trait during an individual’s life to compensate for temporary or local changes in external conditions that alter the optimum lifespan for a particular species population. In addition, genetics discoveries strongly support the evolvability concept to the effect that sexually reproducing species can evolve design features that increase their ability to evolve, and that aging is one such feature.

This article discuss the effects of heat treatment and lubrication modes on the machinability of an A356 alloy (Al-Si-Mg); the alloy is studied as-received, with solution heat-treated alloy (SHT) as well as with an alloy that is solution heat-treated and then aged at 155, 180 and 220 °C. In the course of machinability evaluation, several criteria including cutting force, surface roughness, tool wears and burr analysis (chip) were studied. The results and analysis in this work indicated that the selected machinability criteria are important and necessary to effectively evaluate the machinability of A356 alloys. The machinability of both materials and tools were estimated in terms of cutting force, chip thickness ratio and burr formation, flank wear and roughness. The effects of different cutting parameters (cutting speed and feed rate) and lubrication modes (dry, mist and wet) on the machinability of the A356 cast alloy were also examined. The influence of heat treatments on the burr formation and surface quality was clearly revealed by the experimental results. Experimental work revealed that cutting forces were influenced significantly by aging and cutting speed. However, the different aging at 155, 180, and 220 °C and the cutting speed significantly affected the machinability of the A356 cast alloy. The results obtained show that a better drilling performance in terms of surface quality occurs at a high feed rate, with dry drilling and artificial aging at T6.

Organic electrophoretic coatings have gained significant attention due to their ability to provide a uniform and controlled coating thickness, high coating adhesion, and excellent corrosion protection properties. In this work, to investigate the aging behaviors of an organic electrophoretic coating for magnesium alloys, water absorption kinetics curves of the coatings after immersion in 3.5 wt.% NaCl at 20℃ and 40℃ were measured, and parameters such as the saturated water absorption and saturation time of the free film coatings were fitted to determine the densification evolution of the organic coatings. A tensile test was used to test the tensile strength of the organic coating during service to determine the evolution of the strength and toughness of the organic coating. The evolution of wet adhesion of organic coatings with service time was tested by ASTM D4541-02. The impedance spectra of the organic coatings under the above conditions were detected by EIS, and finally, the failure behavior of the organic coatings under immersion was analyzed.

Development of load-bearing polymer composite constructions in civil engineering, such as industrial chimneys and gas ducts, requires filling some research gaps. These gaps are related to long-term behavior under mechanical and temperature loads, cyclic ones as well. Such conditions mean that viscoelasticity should be considered. First of all, viscoelastic parameters should be calculated, based on the used inner structure model. Then, due to the high working temperatures, thermal aging should be considered as well. This research is devoted to effects of thermal aging on viscoelastic behavior of polymers. Two sets of experiments were conducted: creep tensile tests and cyclic heating in constrained state. The Kelvin-Voigt viscoelasticity model was used to determine the rheological parameters of binder from experimental creep curves. Thermally-aged binder turned out to lose its viscous properties and became elastic. Cyclic heating was used to compare the behavior of normal and thermally-aged binder and to evaluate the possibility of temperature stress accumulation. Similar to creep tests, cyclic heating showed that aged binder lost viscosity and worked almost perfectly elastic. Non-aged binder was prone to stress accumulation much more. As a result, the rheological behavior of aged and non-aged binder was compared and showed a significant difference. In addition, the influence of temperature stress accumulation on stress—strain state was evaluated and turned out to be significant as well. The obtained results can be further used to predict the mechanical behavior of structures made of polymer composites operating for a long time at elevated temperatures, including those exceeding the glass transition temperature.

The aim of the study is to investigate the effects of artificial aging by thermocycling and mechanical loading on force/torque delivery by thermoplastic orthodontic aligners. Ten thermoformed aligners made of Zendura™ thermoplastic polyurethane sheets were aged over two weeks in deionized water by thermocycling alone (n=5) and by both thermocycling and mechanical loading (n=5). The force/torque generated on upper second premolar (Tooth 25) of a plastic model was measured before aging (as control), and after 2, 4, 6, 10, and 14 days of aging, using a biomechanical set-up. Before aging, the extrusion-intrusion forces were in the range of 2.4 to 3.0 N, the oro-vestibular forces were 1.8 to 2.0 N, and the torques on mesio-distal rotation were 13.6 to 40.0 Nmm. Pure thermocycling had no significant effect on the force decay of the aligners. However, there was a significant decrease in force/torque after 2 days of aging for both thermocycling and mechanical loading aging group, which is no longer significant over 14 days of aging. In conclusion, artificial aging of aligners in deionized water with thermocycling and mechanical loading results in a significant decrease in force/torque generation. However, the mechanical loading of aligners has a greater impact than thermocycling alone.

Acquired immunodeficiency syndrome (AIDS) has transitioned from a progressive, fatal disease to a chronic, manageable disease thanks to better defining of antiretroviral therapy, hence contributing to increased life expectancy. In parallel, a growing number of subjects without overt clinical signs of disease but living with chronic HIV infection (people living with HIV, PLWH) are experiencing early cardiovascular disease worldwide. However, a progressive increase in the prevalence of multiple comorbid diseases has been reported as these patients age, including cardiovascular disease (CVD). Cardiovascular mortality can be either directly related to the viral infection, a progressive reduction of response to the antiretroviral therapy, chronic inflammation or lifestyle-related. Cardiovascular ageing represents a relevant issue in the management of HIV-infected patients. Although the exact pathophysiological mechanism that leads PLWH to develop cardiovascular disease is not entirely understood, there is substantial evidence that they accumulate age-related conditions earlier than the general population. Furthermore, since the proportion of PLWH growing older than 50 years has progressively increased, this results in a complex interaction between disease-related pathophysiology and the exposition of a growing burden of cardiovascular risk factors. For this reason, we performed a systematic review of the genes most frequently associated with ageing in HIV-infected subjects, followed by a bioinformatic analysis to explore the biological impact of the genes related to ageing.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

The influence of playing formations and team ranking on the physical performance of professional soccer players is an open question that needs to be explored. The present study aimed to investigate the impact of these factors on the physical exertion of Serie A soccer players. We analyzed match data from 375 players, categorizing teams based on their final ranking and comparing performance across different playing formations. Krustal-Wallies test, and Dunn test with Bonferroni adjustment, revealed that high-ranking (HR) teams exhibited a higher percentage of high-intensity (HI) accelerations compared to mid-ranking teams, suggesting the critical role of HI efforts in achieving favorable match outcomes. Moreover, the 4-3-3 playing formation was associated with greater acceleration demands than other formations, particularly in HR teams. Our study also established benchmarks for various performance metrics, enabling coaches to assess player performance and identify potential signs of overtraining. These findings contribute to a deeper understanding of the physical demands in soccer and offer practical implications for coaches and players in optimizing training and performance strategies.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

As global life expectancy continues to rise, we are challenged with maintaining health into old age, and research has thus concentrated on various strategies aimed at mitigating the effects of skin aging. Aromatic plants stand out as potential sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EO). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with Etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1β protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence associated β-galactosidase and p21/p53 protein levels and nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.

Aging is the important risk factor for tumorigenesis. Metabolic reprogramming is hallmark of both aging and tumor initiation. However, how the crosstalk between aging and metabolic reprogramming affects the tumor microenvironment (TME) to promote tumorigenesis was poorly explored. We utilized a computational approach proposed by our previous work, termed as MMP3C (Modeling Metabolic Plasticity by Pathway Pairwise Comparison), to depict age-related metabolic plasticity using pan-cancer bulk RNA-seq data. Through MMP3C analysis across 17 age-related cancer types, a high metabolic organized heterogeneity was found across those cancer types. Subsequent analysis revealed a higher degree of glycolysis and impaired oxidative phosphorylation in older patients. Similar phenomenon was also observed at the single cell resolution. Many energy generation pathways, i.e., TCA cycle, oxidative phosphorylation were weakened in activated T cells and macrophages, while it increased in exhausted T cells, immunosuppressive macrophages, and Tregs in older patients. It was suggested that aging-induced metabolic switches alter the utilization of glucose, thereby influencing immune function and resulting in the remodeling of the tumor microenvironment. This study provides new insights into the associations between tumor metabolism and TME mediated by aging, linking with novel strategies for cancer therapy.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Structural and morphological properties of the hydronium-potassium jarosite microstructures were investigated in this work, and their electrical properties were evaluated. All microstructures were synthesized at a reasonable temperature of 343 K with a reduced reaction time of 3 hours. Increase in the pH from 0.8 to 2.1 decreased the particle sized from 3 µm to 200 nm and increasing the aging time from 0, 3 to 7 days resulted in semispherical, spherical and euhedreal jarosite structures, respectively. A Rietveld analysis also was done, finding that increasing pH, the amount of hydronium substitution by potassium in the cationic site also increases, having a 77.72 % of hydronium jarosite (JH) plus 22.29 % potassium jarosite (JK) at pH 0.8; 82.44 % (JH) and 17.56 % (JK) at pH 1.1, and 89.98 % (JH) plus 10.02 % (JK) at pH 2.1. The results obtained in this work show that the obtained hydronium potassium jarosite microstructures with reduced particle size and euhedreal morphology can be used as anode materials for improving the life time of lithium ion batteries, due that during the analysis of the voltage obtained using electrodes made with this particles and graphite, this ranged from 0.89 to 1.36 V.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

The effect of retrogression re-aging treatment (RRA) on corrosion behavior of 7055 Al-Zn-Mg alloy were studied. Results provides the corrosion resistance could be greatly improved by RRA. After the RRA treatment, the isolated precipitates occurred on grain boundaries (GBs) and the low angle grain boundaries (LAGBs) presented a larger fraction compared to the single-stage peaking aging. The samples after RRA treatment also show better corrosion resistance than the single-stage peak aging. The results of electrochemical impedance spectroscopy (EIS) show that impedance spectrum is consisted of semi-infinite layer diffusion impedance and stagnant Weber impedance. The semi-infinite layer diffusion impedance corresponded a limited retention layer on the electrode surface. In corrosion process, Weber impedance corresponded to stagnant layer of corrosion products generated by the anode branches. The RRA sample has the high Rf and low Cf, Cp values, and the corrosion current density of the RRA samples is ten times less than the single-stage peak aging samples with the 10% hardness losing.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

The aim of this study is to study the effect of aging in different media (deionized water and artificial saliva) on the force/torque generation by thermoplastic orthodontic aligners. Ten thermoformed aligners made of Essix ACE® thermoplastic sheets were aged in deionized water and in artificial saliva over two weeks at 37 C, five in each medium. The force/torque generated on upper second premolar (Tooth 25) of a resin model was measured at day 0 (before aging), 2, 4, 6, 10, and 14, using a biomechanical test set-up. The results showed that the thermocycling of aligners has no significant impact on their force/torque decay. No significant differences were also found in force/torque between the aligners stored in deionized water nor artificial saliva. The vertical extrusion-intrusion forces were measured in the range of 1.4 to 4.6 N, the horizontal oro-vestibular forces were 1.3 to 2.5 N, while the torques on mesio-distal rotation were 5.4 to 41.7 Nmm. It could be concluded that the influence of saliva on the mechanical properties can be classified as insignificant, and no significant difference between artificial aging in deionized water or artificial saliva was observed.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

Oxidative stress and chronic inflammation, both at the systemic and central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose. To investigate the oxidative stress, inflammatory, and Tau-phosphorylation lowering effects of pomegranate polyphenols (PP) (punicalagin, ellagic acid, peels, and arils extracts). Methods. We used flow cytometry to quantify protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific markers (CD86 and CD163) expression in human microglia HMC3 cells. IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PP on human amyloid beta 1-42 (Aβ1-42)-induced oxidative stress was assessed in microglia by measuring ROS generation and lipid peroxidation, using respectively two ′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substances (TBARS) tests. Neuronal viability and cell apoptotic response to Aβ1-42 toxicity were assayed using the MTT (3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and the annexinV-FITC apoptosis detection kit; respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PP to modulate Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results. Our data indicate that PP was significantly (p<0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) (in U373-MG astrocytes and THP1 macrophages) and decreasing proinflammatory markers (IL-1β) expression in THP1 macrophages. PP was also significantly (p<0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p<0.05) beneficial impact on oxidative stress, illustrated in the reduction of TBARS and ROS generation. Our treatments have significant (p<0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p<0.05) increases pTau-181. This effect was significantly (p<0.05) attenuated by arils, peels, and punicalagin and drastically reduced by ellagic acid treatments. Conclusion. Our results are attributed to PP's anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau pathology potential. Future studies should aim to extend our knowledge of the potential role of PP on A1-42-induced neurodegeneration, mainly its association with the tauopathy involved in AD.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2,256 documents, leading to the selection of 15 clinical trials for synthesis. Here we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

The last decade has seen remarkable progress in the characterization of methylation clocks that track biological age in humans and many other mammalian species. While the biological processes of aging that underlie these clocks have remained unclear, several clues have pointed to a link to developmental mechanisms. These include the presence in the vicinity of clock CpG sites of genes that specify development, including those of the Hox (homeobox) and polycomb classes. Here we discuss how recent advances in programmatic theories of aging provide a framework within which methylation clocks can be understood as part of a developmental process of aging. This includes how such clocks evolve, how developmental mechanisms cause aging, and how they give rise to late-life disease. The combination of ideas from evolutionary biology, biogerontology and developmental biology open a path to a new discipline, that of developmental gerontology (devo-gero). Drawing on the properties of methylation clocks, we offer several new hypotheses that exemplify devo-gero thinking. We suggest that polycomb controls a trade-off between earlier developmental fidelity and later developmental plasticity. We also propose the existence of an evolutionarily-conserved developmental sequence spanning ontogenesis, adult development and aging, that both constrains and determines the evolution of aging.

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and treatment response are typ-ically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immuno-histochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In con-trast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying tumor volume using the HALO® AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for reliable high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing in-sights for preclinical research design.

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Pipelines extend thousands of kilometers to transport and distribute oil and gas. Given the challenges often faced with corrosion, fatigue, and other issues on steel pipes, the demand for glass fiber reinforced plastics (GFRP) pipes is increasing in the oil and gas gathering and transmission systems. However, the medium transported through these pipelines contains multiple acid gases such as CO2 and H2S, as well as ions including Cl-、Ca2+、Mg2+、SO42-、CO32- and HCO3-. These substances can cause a series of problems, such as aging, debonding, delamination, and fracture. In this study, a series of aging damage experiments were conducted on V-shaped GFRP pipes with depths of 2mm and 5mm. The aging and failure of GFRP were studied under the combined effects of external force and acidic solution using acoustic emission (AE) techniques. It was found that the acidic aging solution promoted matrix damage, fiber/matrix desorption, and delamination damage in GFRP pipes over a short period. However, the overall aging effect was relatively weak. Based on the experimental data, the SSA-LSSVM algorithm was proposed and applied to the damage pattern recognition of GFRP. An average recognition rate of up to 90% was achieved, indicating that this method is highly suitable for analyzing AE signals related to GFRP damage.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Converting biowaste into biochar and subsequently putting it into the soil are considered to be an effective approach to sequestrate carbon (C). However, biochar will inevitably undergo the aging process in soil, which influences its stability, and ultimately threatens its carbon sequestration ability. This study selected CaCl2 as exogenous additive of sewage sludge and bone dreg to quantify both surface C and bulk C stability in Ca-rich biochars under three aging processes (dry-wet aging, freeze-thaw aging, and natural aging in farmland soil), and revealed the influence mechanisms of exogenous Ca on biochar stability. Results showed that after dry-wet aging (25 rounds), freeze-thaw aging (25 rounds), and natural aging in different farmland soils (5 months), oxidized surface C in Ca-rich biochar decreased by 10~23%, 28~41%, and 0~74%, respectively, compared to that in pristine biochar, while oxidized bulk C decreased by 6~10%, 0~1%, and 0~35%, respectively. Under three aging processes, the surface C and bulk C stability in Ca-rich biochar were superior to that in corresponding pristine biochar, which was attributed to the “protective effect” of Ca-containing crystals on biochar surface, including CaO, Ca5(PO4)3Cl, Ca5(PO4)3(OH), Ca8H2(PO4)6·H2O and Ca10(PO4)6(OH)2. These Ca-containing crystals could block the connection between biochar-C and the external oxidizing environment, intervening the oxidation of C-C/C=C in biochar, but also prevented aging from damaging C structure of biochar, reducing the generation of fragmented structure. By comprehensively assessing surface C and bulk C stability under three aging processes, final C sequestration in Ca-rich biochar increased to 27~80%, compared to that in pristine biochar (23~74%). Therefore, Ca-rich biochar is more dominant than pristine biochar, considering C sequestration potential during long-term aging in soil.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECM), which are important for tissue structure, function and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them and we found that many longevity-assurances pathways re-activate de-novosynthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype”, to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Interestingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point towards novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Physical activity (PA) benefits are well-established, yet many US adults fail to meet PA guidelines. This is especially true for minorities facing social inequities. This study explored barriers and facilitators to PA among urban Midwestern minorities using a mixed-methods approach framed on the socio-ecological model. A cross-sectional survey was conducted among community-dwelling minorities. Participants were grouped as completing low (LLPA) or high (HLPA) weekly leisure-time PA for comparison. Quantitative analysis included MANOVA, follow-up ANOVAs, and calculation of effect sizes. Qualitative data were assessed using inductive thematic analysis. Twenty-nine adults (44.83% Black, 41.37% Latino) participated in the study. The HLPA group (n = 18) reported higher leisure-time PA (p = 0.001, d = 2.21) and total PA (p = 0.02, d = 1.00) compared to the LLPA group (n = 11). LLPA participants faced more personal barriers to PA (p = 0.02, d = -0.92). Common barriers identified in the interviews included a lack of time and financial costs. Facilitators included social support and available PA facilities. Both groups achieved USPA guidelines through different PA domains. Increasing social support and lowering PA-related costs could enhance participation. Addressing barriers and leveraging existing facilitators are crucial to increasing PA among minorities.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p&lt;0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p&lt;0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p&lt;0.001), and were biologically older than COPD patients (p&lt;0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

As the world's population ages and the resulting health problems become more serious, medical and health policies in developed countries are focused on how to prevent and treat the diseases of the aging population and how to maintain their quality of life. Typical age-related diseases include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, and dementia. Although the mechanisms by which these diseases develop differ, they are all caused by the accumulation of molecular and cellular damage over time. In addition, age-related diseases can cause a decline in physical and mental functions and the ability to perform activities of daily living, as well as the loss of roles in society and a sense of fulfillment in life. Therefore, there is a need for treatment and measures to accurately grasp and maintain their quality of life.

Abstract: Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. We identified several genes that appear to be involved both in natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved confirmed their possible roles in aging, suggesting the need for further in vitro and in vivo research. The graphical abstract illustrates the analysis workflow we used and will introduce in the following as an example to demonstrate the power of omics and bioinformatics.

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

For the past few decades, researchers have been intrigued with glassy polymers, which have applications ranging from gas separations to corrosion protection to drug delivery systems. The techniques employed to examine the sorption and diffusion of small molecules in glassy polymers are the subject of this review. Diffusion models in glassy polymers are regulated by Fickian and non-Fickian diffusion, with non-Fickian diffusion being more prevalent. The characteristics of glassy polymers are determined by sorption isotherms, and different models have been proposed in the literature to explain sorption in glassy polymers during the last few years. This review also includes the applications of glassy polymer. Despite having so many applications, current researchers still have difficulty in implementing coating challenges due to issues like as physical ageing, which is briefly discussed in the review.

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Pharmacological and genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Senescent cells have an altered secretome, which may have an autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton. The review was written following an extensive literature survey of published studies, mostly excluding articles published on pre-print servers. The review discusses potential therapeutics targeting cellular senescence and the senescent secretome as underlying pathogenesis of an aging bone.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Dielectric elastomers, such as thermoplastic polyurethanes (TPU), are widely used as dielectric layer, emulation layer and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become an urgent need to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This article reports a device for in-situ measuring the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.47 to 2.94. In addition, combined Fourier-transform infrared spectroscopy, X-ray scattering technique, and atomic force microscopy have been utilized to characterize the evolution of microstructure under strain. The investigation under tensile strain reveals that a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction of the dielectric constant parallel to the electric field in TPU. Our work provides valuable experimental reference for improving the stability of flexible sensors and actuators based on dielectric elastomers.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

The popular appreciation of dry white wines is most frequently directed to young wines. However, present consumption trends comprise the valorisation of aged dry white wines. Therefore, the present work was aimed at the sensory analysis of these wines with different ages to define their sensory space and to understand which factors drive their quality evaluation by experienced tasters (critics, oenologists and students). Individuals were asked to evaluate several synthetic and aesthetic attributes and to characterise the analytic sensory profile through a Check-All-That-Apply (CATA) methodology. The quality evaluations were differently correlated with wine synthetic parameters according to the taster group. For both critics and oenologists, overall quality scores were driven by persistence and complexity. Moreover, quality was also highly correlated with power for critics and with balance for oenologists. Quality scores were highly correlated with wine browning (absorbance at 420 nm) for critics. The tasting panel showed a homogeneous analytic description of aroma, taste and mouthfeel consistent with wine age. The different ages could be associated to a continuous sensory space characterised by a decreasing perception of freshness and increase in mature and mellowed descriptors. All wines shared an austere in-mouth perception elicited by their acidity, saltiness, bitterness, smoothness and dryness. The age prediction showed that most tasters failed to guess the age wines with more than roughly 13 years old, indicating that tasters were not familiar with the sensory features of white wines with 17 to 46 years old. In conclusion, experienced tasters consistently described the sensory space and recognised the high quality of aged dry white wines. Education programs may use the defined sensory spaces according to aging and to expand the range of quality perception by consumers.

Currently, the use of recycled waste plastic in road construction is not just considered ecofriendly but also considered advantageous for improving road performance over time. This research explores using recycled plastic bags, made of low-density polyethylene (LDPE), in asphalt mixtures to improve road performance and manage waste. The study aims to assess the effects of incorporating different amounts of shredded waste plastic into asphalt mixes and determine the optimal percentage. The aggregate used was obtained from Sargodha quarry Pakistan and asphalt used was 60/70 grade obtained from national refinery limited Pakistan. Using the Marshall mix design, the optimum bitumen content (OBC) was found to be 4.5% of the asphalt mix weight. Thirty samples were tested with waste plastic proportions of 6%, 8%, 10%, 12%, and 14% of OBC weight, along with a standard mix. Tests on stability, bulk density, flow, and air voids showed that a 10% plastic content significantly enhances asphalt performance, increasing stability by around 25%. The study recommends using 10% plastic by OBC weight in asphalt mixes for better performance and suggests further research on optimal incorporation techniques of waste materials in asphalt mixtures.

The leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment - surgery, radiation, and chemotherapy - on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

Background: Aging impacts semantic abilities, therefore semantic exercises might be a valuable tool for cognitive stimulation in healthy older adults. However, programs in this area are limited. Methods: In the current paper, we adapted the BOX linguistic semantic program for online use via the CerUp platform. Our goal was to prepare the optimization future experience of CerUp users, including potential changes in task structure, level of difficulty and instructions, and participants’ adherence, engagement, performance accuracy, perceived difficulty, and adequacy ratings assigned to the instructions we provided that might guide future changes. Additionally, we created a map of hypothesized task-specific features that may guide tailor-made uses of the program. Results: To that end, we present preliminary results on the usability of CerUp. By analyzing task-specific usability data alongside the hypothesized map of task-specific features, we also tested the validity of the latter. Conclusions: These preliminary results on the usability of the CerUp platform highlight the potential of programs for semantic stimulation. Such findings can inform future optimizations of the program, tailored to users’ needs and effectively supporting overall language skills and general cognition.

Brain aging in mammals is characterized by morphological and functional changes of neural cells. Macroscopically, this process leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron defiance and behavioral disorders as well. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing an enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro. Among them, cell cycle arrest, increased lysosomal activity, telo-mere shortening, oxidative stress and DNA damage. The most common markers for senescence identification were identified in: i) proteins implicated in cell cycle arrest, such as p16, p21, p53 ii) increased lysosomal mass iii) increased reactive oxygen species (ROS) and senescence associated secretory phenotype (SASP) expression. Finally, dys-functional autophagy, a process occurring during aging, contributes to alter brain homeostasis. The aim of this review is to summarize and update the most recent knowledge about brain aging with a comparative approach, where similarities and differences in some mammalian species are considered.

We investigate the impact of aging on exchangeable inter-arrival times in mixed renewal processes, exploring its implications for reliability and survival analysis. In this study, first, we revisit the definition of renewal point processes, where inter-event time intervals are considered as exchangeable non-negative random variables. Then, we define the concept of statistical aging as latency in the observational process of event counting. Latency affects event detection but preserves exchangeability. However, it may alter the statistical properties of inter-event time intervals. Our analytical and numerical assessments highlight the significance of aging in exchangeable lifetimes, offering insights into key metrics such as the failure survival function, renewal function, and hazard rate function. Through archetypal examples and empirical findings, we illustrate the implications of aging on renewal processes. In particular, employing a Bayesian perspective, we analyze high-frequency currency exchange rate data to assess the impact of aging on volatility risk evaluation. This study contributes novel insights to the literature of renewal theory and survival analysis, emphasizing the role of latency aging in stochastic point processes under exchangeability assumption.

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in young and senescent brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and require additional efforts from researchers, clinicians and nutritionists in the field.

In large-capacity energy storage systems, instructions are decomposed typically using an equalized power distribution strategy, where clusters/modules operate at the same power and durations. When dispatching shifts from stable single conditions to intricate coupled conditions, this distribution strategy inevitably results in increased inconsistency and hastened system aging. This paper presents a novel differentiated power distribution strategy comprising three control variables: the rotation status, the operating boundaries for both Depth of Discharge (DOD) and C-rates (C) within a control period. The proposed strategy integrates an aging cost prediction model developed to express the mapping relationship between these control variables and aging costs. Additionally, it incorporates the multi-colony particle swarm optimization (Mc-PSO) algorithm into the optimization model to minimize aging costs. The aging cost prediction model consists of three functions: predicting health features (HFs) based on the cumulative charge/discharge throughput quantity and operating boundaries, characterizing HFs as comprehensive scores, and calculating aging costs using both comprehensive scores and residual equipment value. Further, we elaborated on the engineering application process for the proposed control strategy. In the simulation scenarios, this strategy prolonged the service life by 14.62%, reduced the overall aging cost by 6.61%, and improved module consistency by 21.98%, compared with the traditional equalized distribution strategy. In summary, the proposed strategy proves effective in elongating service life, reducing overall aging costs, and increasing the benefit of energy storage systems in particular application scenarios.

Lignin fibers typically influence the mixture performance of stone matrix asphalt (SMA), such as strength, stability, durability, noise level, rutting resistance, fatigue life, and water sensitivity. However, limited studies were conducted to analyze the influence of fibers on the percent voids in mineral aggregate in bituminous mixture (VMA) during the mixture design. This study analyzed the effect of different fibers and fiber contents on the VMA in SMA mixture design. A surface-dry condition method test and Marshall Stability test were applied on the SMA mixture with four different fibers (i.e., flocculent lignin fiber, mineral fiber, polyester fiber, blended fiber). The test results indicated that the bulk specific gravity of SMA mixtures and asphalt saturation decreased with the increasing fiber content, whilst the percent air voids in bituminous mixtures (VV), Marshall Stability and VMA increased. Mineral fiber had the most obvious impact on the bulk specific gravity of bituminous mixtures, while flocculent lignin fiber had a minimal impact. The mixture with mineral fiber and polyester fiber had significant effects on the volumetric properties, and, consequently, exhibited better VMA over the conventional SMA mixture with lignin fiber. Modified fiber content range was also provided, which will widen the utilization of mineral fiber and polyester fiber in the applications of SMA mixtures. The mixture evaluation suggested no statistically significant difference between lignin fiber and polyester fiber on the stability. The mineral fiber required a much larger fiber content to improve the mixture performance than other fibers. Overall, the results can be a reference to guide SMA mixture design.

This study aimed to evaluate the impact of different closures used in second fermentation on the aromatic fraction of sparkling wine. Six types of closures (cork stoppers and screw cap) and 94 months of aging in bottle were investigated. Head-space-solid phase microextraction (HS-SPME) and thermal desorption (TD) procedures coupled to gas chromatography-mass spectrometry (GCMSMS) analysis was applied. The vectors containing the relative abundance of the volatile compounds are compositional vectors. The statistical analysis of compositional data requires specific techniques that differ from standard techniques.101 volatile compounds were identified. HS-SPME extracted highest percentage of ester, ketones and other compounds while TD was a useful tool for the obtention of alcohol, acid, ether and alkanes compounds. Esters was the most abundant family of compounds. Compositional data analysis applied to study the impact of different closures used in bottle-aging after second fermentation on the volatile composition of sparkling wine concluded that there are differences in the relative abundance of certain volatile compounds between cork stoppers and screw cap closures group. Overall, the most abundant part in screw cap closures was Ethyl hexanoate and, Ethyl octanoate in cork stoppers. Also, the proportion amount of Dimethylamine was higher in screw cap closures than cork stoppers group relative to the entire of the sample.

This study used Dutch potatoes at the end of dormancy as the material to explore the impact of menthol (0.2 and 0.5 g/kg based on potato mass) treatment on sprouting inhibition and potato quality. The findings revealed that a menthol concentration of 0.5 g/kg effectively inhibited potato tuber sprouting and significantly reduced glucoside alkaloids production. After a storage period of 15 days, the sprouting percentage and glucoside alkaloids content of potatoes treated with 0.5 g/kg menthol were observed to be significantly lower at 4.17% and 68.63 mg/kg, respectively, compared to the control group which exhibited values of 100% and 282.01 mg/kg, respectively (P < 0.05). Throughout the storage period, 0.5 g/kg of menthol promoted respiration, reduced malondialdehyde production in potatoes, inhibited polyphenol oxidase activity, and slowed down tissue browning. Additionally, it mitigated the decline in starch and soluble protein content, inhibiting the accumulation of reducing sugars.

Senescence-accelerated mouse prone 8 (SAMP8) mice exhibit cognitive defects and neuron loss with aging, and are used to study anti-aging effects of Dendrobium nobile alkaloids (DNLA). SAMP8 mice were orally given DNLA from ages 6 to 10 months. At 10 months of age, behavioral tests and neuron damage were evaluated. Protein was extracted and subjected to phosphorylated proteomic analysis. The cognitive deficits and neuron loss in hippocampus and cortex of aged SAMP8 mice were improved by DNLA. Hippocampal proteomic analysis showed differentially expressed protein/genes in SAMP8 compared to age-matched senescence-accelerated resistant mice, including altered tubulin binding, microtubule binding, etc. via Gene Oncology. KEGG revealed endocytosis, mRNA surveillance, tight junction, protein processing in endoplasmic reticulum, aldosterone synthesis and secretion, and glucagon signaling pathway changes. Upregulated protein/genes in the hippocampus of SAMP8 mice, such as Lmtk3, Usp10, Dzip1, Csnk2b, and Rtn1, were attenuated by DNLA; whereas downregulated protein/genes, such as Kctd16, Psd3, Bsn, Atxn2l, and Kif1a, were rescued by DNLA. The aberrant protein/gene expressions of SAMP8 mice were correlated with transcriptome changes of Alzheimer’s disease in the GEO database, and were attenuated by DNLA. Thus, DNLA improved cognitive dysfunction and ameliorated neuronal injury in aged SAMP8 mice, and attenuated aberrant protein/gene expressions.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.

The gut microbiome known as the “hidden organ” in humans has received wide attention due to its pivotal role in human health, influencing various physiological functions and metabolic processes. Multiple factors influence the gut microbiome and diet emerging as a prominent determinant. Increasing evidence verifies different dietary patterns modulate gut microbial composition and its functionality. Asia, home to the world's largest population, showcases immense diversity, reflected in its complex dietary patterns influenced by tradition and modernization. A plethora of research evidence proves Asian diet confers beneficial effects on maintaining and improving health through favorable alteration of gut microbiome. Yet up to date, no comprehensive review exists on the influence of the Asian diet on gut microbiome. This review critically examines published data on dietary components from Eastern, Southeastern, Southern, Western and Central Asian diet and their interaction with the human gut microbiome across healthy and diseased states. It identifies strengths and limitations in Asian gut microbiome research. Asia experiences rapid dietary transitions demanding further investigation into their effects on the gut microbiota. However, evidence proves traditional Asian diets hold promise for developing personalized dietary interventions and therapeutics to promote gut health and prevent chronic diseases by modulating gut microbiome.

Micro plasma devices (MPD) with power gains are of interest in applications involving operations in the presence of ionizing radiations, in propulsion, in control, amplification of high power electromagnetic waves, and in metamaterials for energy management. Here we review and discuss MPDs with an emphasis on new architectures that have evolved during the past 7 years. Devices with programmable impact ionization rates and programmable boundaries are developed to control the plasma ignition voltage and current to achieve power gain. Plasma devices with 1-10 μm gaps are shown to operate in the sub-Paschen regime in atmospheric pressures where ion-assisted field emission results in a breakdown voltage that linearly depends on the gap distance in contrast to the exponential dependence dictated by the Paschen curve. Small gap devices offer higher operation frequencies at low operation voltages with applications in metamaterial skins for energy management and in harsh environment inside nuclear reactors and in space. In addition to analog plasma devices, logic gates, digital circuits, and distributed amplifiers are also discussed.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin may to some extent exacerbate every other kind of age-related damage. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss a method of removing it from single cells in vitro.

The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and large extent of non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as autotetraploid and diploid dosage, plus allele ratios) and SNP marker subsetting (all available SNPs; only genic regions; only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used Genotyping by Sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and onset of flowering, assessed on 143 genotyped plants from a genetically-broad European reference population and their phenotyped half-sib progenies. Results: On average, allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), SNP subsetting offered an advantage compared with any tested subsettings (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting reached better performances. We also released Legpipe2, a SNP calling pipeline tailored for reduced representation (GBS, RAD) medium-sized genotyping experiments.

Rasagiline (Azilect®) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symp-tomatic benefit in Parkinson’s disease (PD) treatment and found to exert preclinical neuroprotec-tive effects. Here, we investigated the neuroprotective signaling pathways of rasagiline in the PC12 neuronal cultures exposed to an ischemic-like insult. Exposure of neurons to oxy-gen-glucose deprivation for 4 h followed by 18 h of reoxygenation caused 40% aponecrotic cell death. Rasagiline induced dose-dependent neuroprotection by decreasing cell death and produc-tion of the neurotoxic reactive oxygen species, and reducing the nuclear translocation of glycer-aldehyde-3-phosphate dehydrogenase (GAPDH). Rasagiline increased protein kinase B (Akt) phosphorylation and decreased protein expression of the ischemia-induced α-synuclein protein, in correlation to the neuroprotective effect. Treatment with rasagiline induced nuclear shuttling of transcription factor Nrf2 and increased the mRNA levels of the antioxidant enzymes heme oxy-genase-1, (NAD (P) H- quinone dehydrogenase, and catalase. These results indicate that rasagiline provides neuroprotection in the ischemic neuronal cultures with inhibition of α-synuclein and GAPDH-mediated aponecrotic cell death, and via mitochondrial protection, as by increasing mi-tochondria-specific antioxidant enzymes by a mechanism involving the Akt/Nrf2 redox-signaling pathway. These findings may be exploited for neuroprotective drug development in PD and stroke therapy.

While the number of publications on wine and health is steadily increasing, ranging from molecular level to epidemiological studies, often with contradictory results, little attention has been given to an holistic approach. In this review some unusual concepts are considered, such as phytocomplex, vehicle and the Matrix effect. As an example, three mono/polyphenols present in wine, Tyrosol, Hydroxytyrosol and Resveratrol, have been selected and the consequences of respecting, disregarding or ignoring the Matrix effect are shown. Underestimation of the wine Matrix effect could lead to deceiving results, as in the case of de-alcoholized wine or wine-compound-based nutritional supplements,or in emphasizing a single component toxic activity, in this case alcohol, ignoring the specific protective action at molecular level of other compounds (polyphenols) present in the same Matrix. The dark side of Matrix effect is also discussed. It is suggested that specificity of wine should be always taken in consideration by public health Authorities.

Tobacco smoke is an environmental mixture including polycyclic aromatic hydrocarbons and may interfere in endocrine system as an EDC in aging. Thus, we performed a molecular epidemiological approach with in-depth biological monitoring of combustible cigarette smoking among adolescents and adults in South Korea (N=620) with exposure biomarkers, i.e., exhaled CO, urinary cotinine, t,t-muconic acid (TTMA), malondialdehyde (MDA), and obtained information of their lifestyle and tobacco addiction status. We also diagnosed the genetic polymorphisms on the 96 SNPs for tobacco-metabolism, -addiction, and expression differences and compared mtDNA abnormalities in buccal and blood cells. As results, there were positive associations among the above tobacco exposure biomarkers. Man or youth smokers showed high frequency in some of mtDNA alteration, such as ‘SNPs for inconsistent bases between buccal and blood cells’. Among the SNPs, the polymorphisms on SULT1A1, DRD2, and ADH1B were related to multi-exposure biomarkers. Interestingly, youth showed similar levels of urinary TTMA and MDA to adults, although their pack-year was approx. 1/6 volume of that of adults. We also observed the negative association between urinary MDA levels and the growth rate in the adolescents (p<0.05). In conclusion, the present biological monitoring provides high susceptible population, i.e., adolescents rather than adults, and reliable genetic factors affecting tobacco exposure. The inferred environment-gene-gene interaction suggests tobacco smoking accelerats aging in adolescents as an EDC.

Abstract: Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but extant studies are limited in interval of assessment (2-5 years). We studied cognitive performance in a cohort of survivors and controls utilizing cross-sectional cognitive performance data from age 60 to 89 years as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5– to 15-year survivors (N=328) and non-cancer controls (N=158) were assessed at enrollment and at 8, 16 and 24 months with standard neuropsychological tests and comprehensive geriatric as-sessment. Results: Cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower than controls in learning and memory (LM) but not in attention, processing speed and executive function (APE). Younger survivors, i.e., those under 75 years of age, exhibited early decline in performance in both LM and APE compared to controls, with no differences between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Differences between survivors and controls were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.

Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify. This arises particularly because the functionally interconnected nature of biological systems constrains the simultaneous optimization of coupled traits (interconnection constraints), or because individual traits cannot evolve (impossibility constraints). We present an account of aging that integrates AP and biological constraint with recent programmatic aging concepts, including costly programs, quasi-programs, hyperfunction and hypofunction. We argue that AP mechanisms of costly programs and triggered quasi-programs are consequences of constraint, in which costs resulting from hyperfunction or hypofunction cause senescent pathology. Impossibility constraint can also cause hypofunction independently of AP. We also describe how AP corresponds to Stephen Jay Gould’s constraint-based concept of evolutionary spandrels, and argue that pathologies arising from AP are bad spandrels. Biological constraint is a missing link between ultimate and proximate causes of senescence, including diseases of aging. That this was not realized previously may reflect a combination of hyperadaptationism among evolutionary biologists, and the erroneous assumption by biogerontologists that molecular damage accumulation is the principal primary cause of aging.

The universal chirality is the commonly accepted view of nature. Biological chirality is the distinct part of the more general phenomena. Following this view, all living organisms are characterized by the non-equilibrium state of their molecular constituents. From the thermodynamic perspective, the non-equilibrium state of biomolecular ensemble holds inevitable consequences being the substrate of spontaneous reactions directed to equilibrium (not associated with life) state. At the protein level, spontaneous biological reactions represent the natural part of proteins' post-translational modifications (PTMs). The essential contribution to the origin and maintenance of the non-equilibrium state belongs to prevalent bio-molecular chirality. Correspondently, spontaneous PTMs such as racemization and glycation, working against life-supporting prevalent chirality, are known as the significant determinants of protein misfolding, dysfunctions, and aggregation. Accumulation of aberrant protein during life-span allows consideration of time-dependent spontaneous racemization and glycation as protein aging. Spontaneous PTMs of proteins is occurring in the interaction with other forms of enzymatic and non-enzymatic PTMs. In this review, we are considering the contribution of spontaneous racemization and non-enzymatic glycosylation to protein aging.

Skin aging is one of the most common problems facing humanity. It occurs because of altering the balance between free radicals and antioxidants and increasing the amount of the reactive oxygen species (ROS) in skin cells, which leads to oxidative stress especially when exposed to UV radiation. Antioxidants can neutralize the harmful effects of ROS, and secondary plant metabolites can help protect against UV radiation. In this study, punicalagin was extracted from pomegranate and concentrations of total polyphenolics and flavonoids were determined and antioxidant activities measured. Punicalagin was loaded onto niosomes and its morphology and release were studied. An in vitro study was performed on human fibroblast cell line HFB4 cells with aging induced by H2O2 and UV radiation. Cell cycle arrest was studied and different genes (MMP3, Col1A1, Timp3, and TERT) involved in the skin aging process were selected to measure punicalagin's effect. Punicalagin succeeded in reducing the growth arrest of HFB4 cells, activated production of the Col1A1 and Timp3 genes, maintained collagen level, and lowered of MMP3. Punicalagin increased human TERT concentration in skin cells. Punicalagin is promising as a natural antioxidant to protect human skin from aging.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

Revealing the spatial distribution mechanism of the coupling effect between soil water and salt is essential for managing saline-alkali farmland. This study utilized the multifractal method to analyze soil water and salt under varying water content levels in arid saline-alkali farmland. Soil samples were collected on the second (S1), fifth (S2), eighth (S3), eleventh (S4), and fourteenth (S5) days after a rainfall event. The findings showed that a significant decrease in soil water content, contrasting with an increase in soil salt content throughout the soil layers post-rainfall. As water content decreased, the spatial variability of soil water initially increased from S1-3 and then decreased, while the spatial variability of soil salt decreased. The spatial distribution between soil water and salt exhibited a high correlation at S3-4 (with relative water content of soil ranging from 0.52 to 0.75) due to their coupling effect. However, soil salt was unevenly leached by rainfall at high water content levels (S1-2) and precipitated at low water content levels (S5), resulting in low spatial variability correlations between soil water and salt. This study elucidated the coupling process of soil water and salt, identifying their spatiotemporal distribution mechanism in dryland agricultural areas.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It is produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia and other anomalies. Importantly, it is associated with chronic pathologies (often age-related) that have an inflammatory component. This includes atherosclerosis, diabetes and Alzheimer’s disease. Its mode of action in these diseases is not well understood, but it inhibits or regulates multiple major pathways. Klotho has a membrane form, and a soluble form (s-Klotho). Cytosolic Klotho is postulated but not well characterized. s-Klotho has endocrine properties that are incompletely elucidated. It binds to the FGF receptor 1c (FGFR1c) that is widely expressed (including endothelial cells). It also attaches to soluble FGF23, and FGF23/Klotho binds to FGFRs. Thus, s-Klotho might be a roaming FGF23 coreceptor, but it has other functions. Notably, Klotho (cell-bound or soluble) counteracts inflammation, and appears to mitigate related aging (inflammaging). It inhibits NF-κB and the NLRP3 inflammasome. This inflammasome requires priming by NF-κB, and produces active IL-1β, membrane pores and cell death (pyroptosis). In accord, Klotho countered inflammation and cell injury induced by toxins, damage-associated molecular patterns (DAMPs), cytokines, and reactive oxygen species (ROS). s-Klotho also blocks the TGF-β receptor and Wnt ligands, which lessens fibrotic disease. Low Klotho is associated with loss of muscle mass (sarcopenia), as occurs in aging and chronic diseases. s-Klotho counters the inhibitory effects of myostatin and TGF-β on muscle, reduces inflammation, and improves muscle repair following injury. Inhibition of TGF-β and other factors may also be protective in diabetic retinopathy and age-related macular degeneration (AMD). This review examines Klotho functions especially as related to inflammation, and potential applications.

Background: Aging rate is affected by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle and environmental factors. In accelerated aging (AA), biological age exceeds the chronological one. Objective: To undertake a critical reappraisal of the AA concept and to reveal its weaknesses and limitations. Methods: We reviewed over 300 recent articles dealing with physiology of brain aging and pathophysiology of neurodegeneration. Results: (1) Organ systems age at different rates, which interferes with application of the AA concept to individual organs. (2) Aging rate can be decelerated due to individual structure–functional reserves built with cognitive, physical training or pharmacological interventions. (3) The AA concept lacks standardised terminology and methodology. (4) Specific molecular biomarkers (MBM) reflect aging. To consolidate the AA theory, researchers should validate numerous MBM candidates. (5) Aging factors, mechanisms and the exact nature of their biological outcomes are not well understood. Conclusion: Although considered as a perspective theory, the AA concept has serious limitations and it requires an update.

Purpose of research was to determine changes in optical quality for monthly disposable soft contact lenses (SCL) wearers with new and monthly worn SCL. Retinal straylight was assessed in SCL wearers using a C-Quant straylight meter. The study included 33 participants (age 22 ± 1.4 years) who wore monthly disposable silicone hydrogel contact lenses. Measurements were taken with month-old SCL that had been worn for no more than 4 hours. Participants then replaced the old lenses with new ones. After a 15-minute adaptation period, straylight measurements were taken with the new SCL. A questionnaire was administered to all participants, inquiring about vision complaints and the type of contact lens material used. The decimal logarithm of the stray-light parameter, log(s), was notably higher with month-old SCL (log(s) = 0.97±0.17) than with brand-new SCL (log(s) = 0.86±0.15), p < 0.001. The average increase in retinal straylight after a month of SCL use was log(s) = 0.11 ± 0.08. The questionnaire revealed that 35% of participants observed a reduction in visual quality after wearing the contact lenses for a month. Results showed that monthly disposable soft contact lenses could reduce visual quality when scheduled replacement time has been reached.

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds in the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of prooxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid, antihypertensive, etc. activity. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements, and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn, in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

Objectives: Stress urinary incontinence (SUI) negatively affects the quality of life and sexual function in women. This study aimed to evaluate the efficacy of radiofrequency (RF) therapy in reducing SUI symptoms and its impact on sexual function. Methods: Thirty-four women with SUI were enrolled and underwent a single RF treatment session using the Viveve® System (Viveve Medical Inc., USA) with parameters of 90 J/cm² and 220 pulses per hour. Assessments at baseline and 6 months post-treatment included perineal ultrasound and personal interviews to evaluate lower urinary tract symptoms and sexual function. Urodynamic studies, voiding diaries, and questionnaires such as the Female Sexual Function Index (FSFI), Overactive Bladder Symp-tom Score (OABSS), Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Question-naire-7 (IIQ-7), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) measured outcomes. Results: RF therapy significantly improved sexual function, with higher FSFI scores in all domains except pain at 6 months. SUI symptoms were significantly re-duced, as indicated by improved scores on OABSS, UDI-6, IIQ-7, and ICIQ-SF, alongside better voiding diary results. Anatomical changes included reduced bladder neck mobility, decreased vaginal width, and a reduced rotation angle of the proximal urethra. Conclusions: RF therapy is effective and safe for treating mild to moderate SUI and enhances sexual function, potentially due to changes in vaginal topography. These results suggest RF therapy as a viable non-surgical op-tion for managing SUI and improving sexual health.

Raru’s plants bark has long been used as traditional medicine in Batak’s tribe. Raru’s bark is derived from several trees that are usually used in a mixture in Batak traditional beverages. This bark is generally used as antidiabetic remedies. This study aims to combine the rarus’s bark extract and mocaf activated-carbon (MAC) in order to study antidiabetics in rats. The combination of raru’s bark extract and MAC were tested on male rats as of Sprague Dawley strain for testing antidiabetic bioactivity. The result showed that antidiabetic activity of raru’s extract and MAC exposed the antidiabetic level declines in rat’s blood. The various treatments of different concentration ratios of raru’s extract and MAC useful in the experiments showed that the levels of blood level reduction were slightly different (14-21%). The raru’s extract pure was observed more effective in decreasing the blood glucose level in rat’s blood, in comparison the positive control. The mixture of raru’s extract and MAC with 75:25 ratio is better than 50:50 ratio. The involvement of MAC in the alleged antidiabetic agent did little in improving the blood glucose level decrease in rat’s blood. Raru’s extract and MAC indicate its potential utilization as an antidiabetic agent.

We aimed to investigate the relationship between membrane material and development of membrane fouling in a membrane bioreactor (MBR) using membranes with different pore sizes and hydrophilicities. Batch filtration tests were performed using submerged single hollow fiber membrane ultrafiltration (UF) modules with different polymeric membrane materials including cellulose acetate (CA), polyethersulfone (PES), and polyvinylidene fluoride (PVDF) with activated sludge taken from a municipal wastewater treatment plant. The three UF hollow fiber membranes were prepared by a non-solvent-induced phase separation method and had similar water permeabilities and pore sizes. The results revealed that transmembrane pressure (TMP) increased more sharply for the hydrophobic PVDF membrane than for the hydrophilic CA membrane in batch filtration tests, even when membranes with similar permeabilities and pore sizes were used. PVDF hollow fiber membranes with smaller pores had greater fouling propensity than those with larger pores. In contrast, CA hollow fiber membranes showed good mitigation of membrane fouling regardless of pore size. The results obtained in this study suggest that the surface hydrophilicity and pore size of UF membranes clearly affect the fouling properties in MBR operation when using activated sludge.

Objective: The influence of gender on the number and pattern of co-morbid psychiatric illness was archivally compared between patients with and without an Alcohol Use Disorder (AUD) among psychiatrically treated individuals drawn from a large Danish birth cohort. Method: By age 45, fifteen percent of the Copenhagen Perinatal Birth Cohort (N=8,109) had been treated in a Danish psychiatric facility. Of those 1,247 patients, 368 were assigned an AUD diagnosis (29.5%). All psychiatric diagnoses assigned to these patients, over all admissions, were classified into one of 14 broad ICD-10 F categories for comparative purposes. Results: More of the patients with an AUD diagnosis were male. Patients with an AUD diagnosis were significantly more likely to receive two or more non-AUD psychiatric diagnoses than patients without an AUD diagnosis. The number of psychiatric diagnoses was greater for female than male AUD patients, a difference not found among male and female patients without an AUD diagnosis. For patients with no AUD diagnosis, the influence of gender on the pattern of psychiatric disorders was similar to that commonly reported. In contrast, the influence of gender on the number and pattern of psychiatric disorders for patients with an AUD diagnosis indicated fewer gender differences. Several diagnostic categories that discriminated male from female patients without an AUD-related diagnosis, no longer discriminated male from female patients with an AUD-related diagnosis. Conclusions: Our findings suggest that gender differences associated with psychiatric comorbidity that have been reported in large heterogenous study, should not be generalized to specific diagnostic groups without further study.

Forests have multifunctional roles. They not only increase forest carbon sinks through afforestation and management, but also indirectly realize multiple benefits of "economy + ecology + society". Therefore, we construct a multiple output-benefit system of forest carbon sinks based on the development of forest carbon sinks in provinces of China. This system is also able to distinguish the importance of forest carbon sinks from other outputs. For the efficiency evaluation of multi-level output systems, this paper constructs a cross-evaluation model based on evidential reasoning method, the original efficiency information by conducting efficiency evaluation before information fusion. Further, the spillover effects and influencing factors of forest carbon sink efficiency are analyzed through a spatial regression model to explore the spatial characteristics of forest carbon sink efficiency in China. The results show that: (1) there is a large gap between the cross-efficiency levels of forest carbon sinks in various regions of China, with significant spatial correlation. For the perspective of direct output benefits, the cross-efficiency of the eastern region is higher, while the cross-efficiency of the northwestern region is lower; for the perspective of indirect output benefits, the cross-efficiency of the southeastern region is higher. (2) China's forest carbon sink has a significant positive spillover effect, and the indirect output cross-efficiency has a significant negative impact on the forest carbon sink in its own region. Further analyzing the impact of indirect output cross-efficiency, it is found that the cross-efficiency of the ecological dimension and the cross-efficiency of the social dimension have a significant negative impact on the forest carbon sink in its own region, and the economic dimension has a significant positive impact on the forest carbon sink in its own region. In conclusion, corresponding policy recommendations are proposed for the development of forest carbon sinks to promote the realization of the dual-carbon goal.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.