In the steel industries, workers are exposed to heat and ambient thermal stresses on a daily basis, leading to discomfort and limited performance. In this study, the main purpose is to investigate the effect of climate heat stress on the rate of accidents in the workplace for workers for 5 consecutive years. The data of this study were received without any sampling through the HSE Center for Steel Industry and meteorological data from 2015 to 2019 from Isfahan Meteorological station. The daily number of casualties among workers in the steel industry during 2015-2019 by adjusting seasonal patterns, months, effects of the day of the week and other meteorological factors on the average daily temperature using the studied model has a decreasing effect. Eviews software (version 8) was used to model and investigate the relationship between events and meteorological variables. The mean temperature was at least 40.2-2 and at most 70.34 ° C, respectively. In the time-series study for the main model, the number of accidents shows a direct relationship with the average temperature and wind speed. Climatic indices of humidity and rainfall have the least impact on accidents compared to temperature and wind speed. A strong correlation was shown between the increase in average ambient temperature and the rate of accidents over the past 5 years. Given the fundamental differences in studies of environmental exposure and wind speed over heat stress, further analysis in workers should be considered.

The use of natural stone has a historical and environmental value that makes it strategically valuable for landscape conservation in Europe. Marble, among others, is widely spread on Earth, and it offers high-performance features in architectural applications. However, the complexity of these formations and the rock variability in different ore bodies require detailed studies of the natural and induced stress state, the fracturing degree, and the influence of external factor (such as temperature and/or chemical agents) on the mechanical properties in order to optimize the exploitation processes by reducing extractive waste. This article shows a series of studies conducted by the authors over the last 20 years aimed at making the exploitation of marble blocks in the Carrara basin safer, more efficient, and, therefore, more sustainable. In particular, studies for increasing the knowledge on the natural and the induced stress state through on-site measurements and numerical modeling, studies to improve the quality of the exploited material through improvements of cutting technologies, studies to improve the knowledge of the mechanical behavior of the material under varying loads and temperature conditions and studies to improve the reuse of water materials and their reduction are reported.

Residual stress (RS) is the most challenging problem in metal additive manufacturing (AM) since the build-up of high tensile RS may influence the fatigue life, corrosion resistance, crack initiation, and failure of the additively manufactured components. While tensile RS is inherent in all the AM processes, fast and accurate prediction of stress state within the part is extremely valuable and would result in optimization of the process parameters in achieving a desired RS and control of the build process. This paper proposes a physics-based analytical model to rapidly and accurately predict the RS within the additively manufactured part. In this model, a transient moving point heat source (HS) is utilized to determine the temperature field. Due to the high temperature gradient within the proximity of the melt pool area, material experience high thermal stress. Thermal stress is calculated by combining three sources of stresses known as stresses due to the body forces, normal tension, and hydrostatic stress in a homogeneous semi-infinite medium. The thermal stress determines the RS state within the part. Consequently, by taking the thermal stress history as an input, both the in-plane and out of plane RS distributions are found from incremental plasticity and kinematic hardening behavior of the metal by considering volume conservation in plastic deformation in coupling with the equilibrium and compatibility conditions. In this modeling, material properties are temperature-sensitive since the steep temperature gradient varies the properties significantly. Moreover, the energy needed for the solid-state phase transition is reflected by modifying the specific heat employing the latent heat of fusion. Furthermore, the multi-layer and multi-scan aspects of metal AM are considered by including the temperature history from previous layers and scans. Results from the analytical RS model presented excellent agreement with XRD measurements employed to determine the RS in the Ti-6Al-4V specimens.

The construction of sustainable urban forests follows the principle that well-being in people is promoted when exposed to tree population. Facial expression is the direct representation of inner emotion that can be used to assess real-time perception in urban forests. The emergence and change of facial expressions for forest visitors are in an implicit process. The reserved character of oriental races strengthens the requirement for the accuracy to recognize expressions through instrument rating. In this study, a dataset was established with 2,886 randomly photographed faces from visitors in a constructed urban forest park and a promenade at summertime in Shenyang City at Northeast China. Six experts were invited to choose 160 photos in total with 20 images representing one of eight typical expressions as angry, contempt, disgusted, happy, neutral, sad, scared, and surprised emotions. The FireFACE ver. 3.0 software was used to test hit-ratio validation as the accuracy (ac.) to match machine-recognized photos with those identified by experts. According to Kruskal-Wallis test on the difference from averaged scores in 20 recently published papers, contempt (ac.=0.40%, P=0.0038) and scared (ac.=25.23%, P=0.0018) expressions cannot pass the validation test. Therefore, the FireFACE can be used as an instrument to analyze facial expression from oriental people in urban forests but contempt and scared expressions cannot be identified.

Liquefaction risk assessment is critical for the safety and economics of structures. As the soil strata of Ramsar area in north Iran is mostly composed of poorly graded clean sand and the ground water table is found at shallow depths, it is highly susceptible to liquefaction. In this study, a series of isotropic and anisotropic consolidated undrained triaxial tests are performed on reconstituted specimens of Ramsar sand to identify the liquefaction potential of the area. The specimens are consolidated isotropically to simulate the level ground condition, and anisotropically to simulate the soil condition on a slope and/ or under a structure. The various states of soil behavior are studied by preparing specimens at different initial relative densities and applying different levels of effective stress. The critical state soil mechanics approach for identifying the liquefaction susceptibility is adopted and the observed phenomena are further explained in relation to the micro-mechanical behavior. As only four among the 27 conducted tests did not exhibit liquefactive behavior, Ramsar sand can be qualified as strongly susceptible to liquefaction. Furthermore, it is observed that the pore pressure ratio is a good indication of the liquefaction susceptibility

Diurnal and seasonal changes of abiotic environmental factors shape plant performance and distribution. Changes of growth temperature and light intensity may vary significantly on a diurnal, but also on a weekly or seasonal scale. Hence, acclimation to a changing temperature and light regime is essential for plant survival and propagation. In the present study, we analyzed photosynthetic CO₂ assimilation and metabolic regulation of the central carbohydrate metabolism in two natural accessions of Arabidopsis thaliana originating from Russia and south Italy during exposure to heat and a combination of heat and high light. Our findings indicate that it is hardly possible to predict photosynthetic capacities to fix CO₂ under combined stress from single stress experiments. Further, capacities of hexose phosphorylation were found to be significantly lower in the Italian than in the Russian accession which could explain an inverted sucrose-to-hexose ratio. Together with the finding of significantly stronger accumulation of anthocyanins under heat/high light these observations indicate a central role of hexokinase activity in stabilization of photosynthetic capacities within a changing environment.

In the last three decades, the robust scientific data emerged, demonstrating that the immune-inflammatory response is a fundamental component of the pathophysiology of major depressive disorder (MDD). Psychological stress and various inflammatory comorbidities contribute to such immune activation. Still, this is not uncommon that patients with depression do not have defined inflammatory comorbidities, and alternative mechanisms of immune activation need to take place. The gastrointestinal (GI) tract, along with gut-associated lymphoid tissue (GALT), constitutes the largest lymphatic organ in the human body and forms the biggest surface of contact with the external environment. It is also the most significant source of bacterial and food-derived antigenic material. There is a broad range of reciprocal interactions between the GI tract, intestinal microbiota, increased intestinal permeability, activation of immune-inflammatory response, and the CNS that has crucial implications in brain function and mental health. This intercommunication takes place within the microbiota-gut-immune-glia (MGIG) axis, and glial cells are the main orchestrator of this communication. A broad range of factors, including psychological stress, inflammation, dysbiosis and other, may compromise the permeability of this barrier. This leads to excessive bacterial translocation and the excessive influx of food-derived antigenic material that contributes to activation of the immune-inflammatory response and depressive psychopathology. This chapter summarizes the role of increased intestinal permeability in MDD and mechanisms of how the "leaky gut" may contribute to immune-inflammatory response in this disorder.

Stress Granules formation is a pro-survival mechanism helping cells to cope with environmental challenges. Stress Granules have been studied for two decades in fundamental research, and are now being examined in the context of human pathogenesis. Here, we review studies highlighting stress granules’ involvement in cancer development through translational pattern modification.

After reviewing cancer theories, cancer treatment development histories, randomized clinical trial's performance, cancer treatment strategy, trial follow-up times, and conducting numerous simulations using existing data, the authors found: (1) medical treatments come with three to four lethal factors: treatment side-effects, emotional distress and chronic dress, lack of exercises or physical inactivity, and excessive nutrition in some cases; (2) clinical trial exaggerates the benefits of fast-acting treatments and underestimates the slow-delivering adverse side effects as a result of statistical averaging, interfering effects of personal lifestyle factors, and insufficient follow-up times; (3) the benefits of medical treatments are limited by chain comparison, where surgery sets up a negative standard relative to the best way for resolving cancer; (4) the strategy of destroying the tumor is unworkable; (5) medical treatments can turn natural cancer growth curve into approximately doubly exponential curve; (6) multiple factor non-medical measures are much more powerful than medical treatments in controlling cancer growth and metastasis rates; and (7) cancer early diagnosis and over treatments are bad strategies that have great adverse impacts on cancer patients. Based on huge increases in cancer growth rate constants, substantial of loss of organ functional capacity, and severe systemic aging-like cellular damages, the authors concluded that medical treatments promote cancer growth and metastasis rates and shorten patient lives in most cases, and the claimed benefits are caused by triple biases of clinical trials. The authors believe that the better strategy for ending the global cancer epidemic is abandoning clinical trails as the research model, changing caner treatment strategy from killing cancer cells to slowing down cancer growth rates by using multiple factors optimization approach in personalized medicine.

Plants and its corresponding botanical preparations have been used for centuries due to their remarkable potentialities in both treatment and prevention of numerous affections. Hundreds of biologically active constituents are present in each whole plant matrice, working in synergism and conferring both its own protection against invaders and even providing promissory bioactive effects for human beings. The worldwide population has devoted increasing attention and preference by medicinal plants use for health promotion and disease prevention, and more recently for oxidative-stress related disorders protection. Indeed, oxidative stress-related disorders, like cardiovascular and (neuro) degenerative disorders, and even cancer have raised exponentially. Although oxidative stress is in itself intrinsic to our own metabolism, allarming sources of free radicals are daily affecting us. In fact, plant-derived bioactives present a broad spectrum of biological effects, and its antioxidant, anti-inflammatory and more recently anti-aging effects have been considered a hot topic among the medical and scientific community. Nonetheless, and although its numerous biological effects, it should not also be forgotten that some bioactive molecules are prone to oxidation and can even exert pro-oxidant effects. In this sense, the objective of the present review is to provide a detailed overview on plant-derived bioactives in oxidative stress-related disorders. Specifically, the role of phytochemicals as antioxidants and pro-oxidant agents is carefully addressed, as is its therapeutic relevance in disease prevention. Finally, an eye-opening look in overall evidence in humans is also ensured.

A study on the selection of hyperelastic constitutive model for polymeric materials is performed using a hybrid experimental-computational approach. Bis-GMA polymer is used as a case study of hyperelastic material to describe the polymer characteristics by determining its Poisson’s ratio and its valid range of the hyperelastic stress-strain curves. These two parameters are then used to determine the hyperelastic constitutive model by using the hybrid approach. Several uniaxial compression tests along with their finite element simulations are implemented in a systematic way, to identify the polymer behavior under the compressive loading conditions. Nano-indentation experiments are conducted to verify the hyperelastic behavior of the polymer. The experimental and computational evidences confirm that the Poisson’s ratio of Bis-GMA is 0.40 and the appropriate hyperelastic constitutive model for this polymer is of a second order polynomial. It is shown that, the results can be used to determine the true stress-strain curve of hyperelastic materials.

A variety of environmental factors contribute significantly to age-related cognitive decline and Alzheimer’s Disease (AD). Nutrition can alter epigenetics, improving health outcomes, which transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in offspring. We feed females SAMP8 with resveratrol-enriched diet during two months prior to mating. Direct exposed F1 generation and the transgenerational F2 generation were investigated. Object novel recognition and Morris water maze demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring resulted from resveratrol fed mother showed increase AMPKα activation, mTOR inhibition and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.

To elucidate dynamic developmental processes in plants, live tissues and organs have to be visualized frequently and for long time periods. The development of roots is studied in depth at a cellular resolution not only to comprehend the basic processes fundamental to maintenance and pattern formation but also study stress tolerance adaptation in plants. Despite technological advancements, maintaining continuous access to samples and simultaneously preserving their morphological structures and physiological conditions without causing damage presents hindrances in the measurement, visualization and analyses of growing organs including plant roots. We propose a preliminary system which integrates the optical real-time visualization through light microscopy with a liquid culture which enables us to image at the tissue and cellular level horizontally growing Brachypodium roots every few minutes and up to 24 hours. We describe a simple setup which can be used to track the growth of the root as it grows including the root tip growth and osmotic stress dynamics. We demonstrate the system’s capability to scale down the PEG-mediated osmotic stress analysis and collected data on gene expression under osmotic stress.

Using hierarchical regression analysis within a mediation model framework, the present study explores direct and indirect (through life satisfaction) causal impacts of commuting stress on turnover intention of employees from 29 business organizations in six populous cities of Turkey. A semi-random heterogeneous sample of 214 employees with different demographics was surveyed in winter and summer times for also capturing seasonal variations of variables. The results supporting the partial mediating role of life satisfaction in the positive relationship between commuting stress and turnover intention infer that commuting stress induces turnover intention directly and indirectly (by reducing life satisfaction). The analysis of variance reveals that demographic characteristics of employees such as gender, marital status, age, and family size together with commuting type and commuting duration matter for their perceived commuting stress, life satisfaction, and turnover intention levels. Commuting stress perception is relatively higher in summer time whereas the other magnitudes are consistently and significantly invariant between two survey implementations. The study concludes with a call for the consideration of commuting stress and life satisfaction together with environmental and demographic factors when analyzing the antecedents and consequences of employee turnover intention.

Although the signaling function of Na/K ATPase is been studied for decades, the chasm between the pumping function and the signaling function of Na/K – ATPase is still an open issue. This article explores the relationship between ion pumping and signaling with attention to the amplification of oxidants through this signaling function. Starting with some experimental observations published by our laboratories and others, we develop some predictions regarding cellular oxidant stress.

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

Failure characteristics induced by unloading disturbance and the corresponding mechanical mechanism of the coal seam floor are important theoretical bases for water-bursting prevention from the floor of the coal seam and rock burst alarm in deep mining. However, the existing two-dimensional ground-pressure-control theory based on shallow mining cannot sufficiently guide deep-mining practices. In this study, the redistribution of mining-induced stress field in rocks surrounding the longwall face and mechanical behaviors of strata in deep mining are investigated through a combination of numerical simulation, physical simulation, and field measurement. Results demonstrate that mining-induced stress fields in the floor of the longwall face differ in space and time. Vertical stress unloading from top to bottom of the floor and horizontal stress unloading are relatively low. A concentration zone of high horizontal stress exists at stope boundaries. The critical yield load of rock stratum in the floor is determined through thin plate yield theory. Under the combined effect of concentrated high horizontal and vertical resilience stresses, strata in the floor fracture from seam to seam if the load increases to the minimum critical buckling value. Fractured strata slide along the fracture surface, which leads to floor heave. The stope floor shows evident time-delay progressive failure characteristics. The stress shell in the stope floor in deep mining is found to be a sensitive mechanical parameter that produces three-dimensional ground-pressure behavior in the floor. This ground-pressure behavior in the stope floor is controlled by the existence of the corresponding stress shell and effects induced by its space–time evolution. This study provides theoretical basis for the dynamic control of a hazard-inducing environment in engineering and minimizing or altering disaster-occurrence conditions during the construction engineering of the coal seam floor.

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

In the current study, the failure behavior of retrofitted steel structures was studied experimentally and theoretically with steel/CFRP double strap joints (DSJs) under quasi-static tensile loading. A series of DSJs with different bonding lengths are also considered and examined to experimentally assess the effective bond length. To predict the failure load values of the tested specimens, a new stress-based criterion, namely the point stress (PS) criterion is proposed. Although some theoretical predictive modelling for the strength between steel/CFRP joints under various loading conditions has been presented, in this work by using the new proposed approach, one can calculate rapidly and conveniently the failure loads of the steel/CFRP specimens. Furthermore, to assess the validity of the new proposed criterion, further experimental data on steel/CFRP DSJs available in the open literature are predicted using the PS criterion. Finally, it was found that a good agreement exists between the experimental results and the theoretical predictions based on the PS criterion.

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

Increased inflammation and heightened physiological stress reactivity have been associated with pathophysiology of depressive symptoms. The underlying biological mechanisms by which inflammation and stress can affect neurogenesis is through alterations of the kynurenine (KYN) pathway, which is activated under stress. Meanwhile, n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation has anti-inflammatory properties and may enhance stress resilience. Whether n-3 PUFA alters stress responsivity KYN is unknown. This placebo-controlled trial examined the effect of n-3 PUFA on KYN metabolism, inflammation, depressive symptoms and mood; and stress-induced changes following a laboratory stressor. Using a placebo-controlled design, 47 healthy male adults were received 4g/d of Omega-3, or a placebo for 12 weeks. A significant group-by-time interaction was found for inflammation markers - gp130 (F= 7.07, p = 0.011), IL-6R alpha (F= 10.33, p = 0.003), and TNF_RI (F= 10.92, p = 0.002). No significant group-by-time interactions were found for mood or depressive symptoms, except for Hedonic Tone (F= 6.50, p = 0.014), neither for KYN metabolites and stress-induced changes to the KYN metabolites and mood following a laboratory stressor. Overall, elevating n-3 PUFAs levels in healthy males ameliorates inflammatory markers but does not ameliorate KYN metabolism, depressive symptoms, mood, or stress responsivity KYN metabolism and mood. The study was registered at ClinicalTrials.gov with identifier NCT05520437 (30/08/2022 first trial registration).

Bee Pollen (BP) has many advantageous properties relying on its multitargeting potential, a new tendency in handling many challenging illnesses. In cancer and neurodegeneration, the antioxidant, anti-inflammatory, immunomodulatory, and antimutagenic effects of BP could be of unequaled importance and need further pharmacological and clinical investigation. Although being still limited, available data interestingly spotlights some floral sources with new and promising activities in-line with this investigation. In addition, we have identified many crucial bioactivities that are widely recognized to individual BP compounds but remain completely untapped in this valuable bee cocktail. A wide range of these compounds have been recently found to be endowed with great potential in modulating pivotal process in neurodegeneration and cancer pathophysiology, such as epigenetic regulation, microbiota composition and function, autophagy, cell death mechanisms, protein misfolding and aggregation and many other effects that we will detail in our current work. In addition, some widely present compounds in BP have only recently been isolated, while the number of studied BPs remain extremely limited compared to the endless pool of plant species that are distributed worldwide. Nevertheless, we have concomitantly elucidated that clinical profits from these promising perspectives are still impeded by some challenging hurdles such as limited bioavailability of the studied phytocompounds, diversity and lack of phytochemical standardization of BP, and the difficulty of selective targeting in some pathophysiological mechanisms. We finally present some interesting insights to guide future research and pave the way for urgent and simplified clinical investigations.

Metallothioneins are multifunctional proteins implicated in various cellular processes. They have been used as biomarkers of heavy metal exposure and contamination due to their intrinsic ability to bind heavy metals and their transcriptional response to both physiological and noxious metal ions such as cadmium (Cd) and mercury (Hg). In this study, we aimed to clarify the role of iron and reactive oxygen species (ROSs) in the induction of the metallothionein system (Mtt) in the ciliate protozoan Tetrahymena thermophila. We investigated the relative mRNA abundances of the metallothionein genes Mtt1, Mtt2/4, and Mtt5, revealing for the first time their responsiveness to iron exposure. Furthermore, by using inhibitors of superoxide dismutase (SOD) and catalase (CAT), alone or in combination with iron, we highlighted the roles of superoxide ion and endogenous hydrogen peroxide, as well as the complex interplay between the metal and ROSs. These results enhance our understanding of the metallothionein system in ciliates and suggest that ROSs may be a primary evolutionary driver for the selection of these proteins in nature.

Background/Objectives: The Perilla frutescens plant has historically been used to protect against inflammation and redox stress. This has been attributed in part to the high content of various polyphenols. Despite this, the complement of polyphenolic components in Perilla extract is not yet fully defined. The aim of this study was to characterise the polyphenolic composition in Perilla extract, and its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which during inflammation and oxidative stress binds to the antioxidant response element (ARE) found on the promoter of phase II antioxidant enzymes. Methods: Following extraction using four solvents of different properties, the total phenolic, flavonoid and ortho-diphenolic content of Perilla extract were determined. Individual phenolic compounds were identified and quantified by RP-HPLC. Dual Luciferase assay using a reporter plasmid containing a human NQO1 ARE-luciferase fusion was employed to determine the potential protective effect of the Perilla fractions against redox stress. Results: HPLC analysis revealed that the highest phenolic content was present in the polar extracts. A total of 35 distinct polyphenolic compounds were identified, with rosmarinic acid being the major constituent. On cells in vitro, the methanol Perilla fraction showed protection against redox stress, with the luciferase assay displaying up to 1.5 fold increase in the induction of the human NQO1 ARE-luciferase reporter. Conclusions: While Perilla extract seems to be mainly protecting against inflammation and redox stress through the action of rosmarinic acid, further work is required on the synergystic effects between different polyphenols.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

This literature review aims to gain a deeper understanding of the anatomy behind the jaw strength of Tyrannosaurus rex and analyze how these features contribute to its predatory behavior. This review will examine various studies and fossil excavations, exploring ideas such as the bite force of T. rex and its variations across different life stages. This will be obtained from numerous biomechanical models of both juvenile and adult Tyrannosaurus rex, as well as reference animals and dinosaurs for comparison. To provide additional information behind T. rex’s hunting techniques, we will also discuss the fauna of herbivorous dinosaurs that were part of T. rex’s diet. Furthermore, we will explore how mandibular stress concentration can vary between ages, a crucial topic in determining what T. rex could consume at certain stages of its life. Finally, we obtain a well-evidenced analysis of the various aspects of Tyrannosaurus rex’s hunting strategies throughout its lifetime.

Grass pea (Lathyrus sativus L.) is a protein-rich crop that is resilient to various abiotic stresses, including drought. However, it is not cultivated widely for human consumption due to the neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP), and its association with neurolathyrism. Though some varieties with low β-ODAP have been developed through classical breeding, the β-ODAP content is increasing due to genotype x environment interactions. This review covers grass pea nutritional quality, β-ODAP biosynthesis, mechanism of paralysis, traditional ways to reduce β-ODAP, candidate genes for boosting sulfur-containing amino acids, and the potential and targets of gene editing to reduce β-ODAP content. Recently, two key enzymes (β-ODAP synthase and β-cyanoalanine synthase) have been identified in the biosynthetic pathway of β-ODAP. We proposed four strategies through which the genes encoding these enzymes can be targeted and suppressed using CRISPR/Cas9 gene editing. Compared to its homology in Medicago truncatula, the grass pea β-ODAP synthase gene sequence and β-cyanoalanine synthase showed 62.9% and 95% similarity, respectively. The β-ODAP synthase converts the final intermediate L-DAPA into toxic β-ODAP whist β-cyanoalanine synthase converts O-Acetylserine into β-isoxazolin-5-on-2-yl-alanine. Since grass pea is low in methionine and cysteine amino acids, improvement of these amino acids is also needed to boost its protein content.

Dark pigmentation can be observed in various parts of the plant, ranging from foliage to petals to berries. The molecular basis of black pigmentation appears to vary among species, with anthocyanins playing a significant role, although specific anthocyanin types and their mechanisms differ. These findings suggest that the development of phenotypes is species-specific or varies between larger taxonomic groups; this is further supported by the polyphyletic nature of dark pigmentation. Additionally, several different regulatory mechanisms have been described for the occurrence of dark pigmentation. Firstly, the repression or knockout of the competing flavone biosynthesis has been shown to lead to darker pigmentation while another mechanism is based on the activation and upregulation of the anthocyanin biosynthesis genes in the presence of MYB transcription factors. Potential ecological functions of dark pigmentation were identified as the protection of the photosynthesis apparatus, camouflage against herbivores, and the attraction of pollinators. Promising industrial applications include microbial factories for the production of natural food colourants, induction of novel phenotypes for the ornamental plant industry and lastly the increase of anthocyanins within agriculturally relevant crops.

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters, and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to baseline. Downstream effects of these catecholamines and corticosterone appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to baseline by the final measurement. DHEA, used as a ratio with corticosterone, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to understanding crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

The delayed effects of radiation alone and combined with skin injury on the kidney are poorly understood. We aimed to unravel and compare the inflammatory, oxidative stress, and survival signaling pathways in the kidney cortex before mice manifested renal dysfunction after these two injuries. Mice were analyzed 30 days post irradiation (9.5 Gy for radiation alone, 9.0 Gy for radiation combined with a skin wound). Radiation alone did not significantly alter BUN, NGAL, or KIM-1 protein levels, indicating preserved kidney function. However, the combined injury had increased KIM-1 protein levels, indicating a nuanced effect on renal health. Radiation and combined injury activated distinct inflammatory pathways. Radiation increased STAT3-Y705 phosphorylation, while combined injury boosted STAT1-Y701 phosphorylation. Additionally, radiation increased mRNA abundance of IFNγR1, IFNγR2, heparanase and IL-10, while combined injury tended to increase heparanase mRNA levels and reduced IL-4 mRNA levels. Both injuries increased the abundance of HO-1 protein, indicating oxidative stress, but radiation alone also reduced MnSOD and catalase proteins. Both injuries promoted AKT1-S473 phosphorylation and diminished p53 protein levels, suggesting inhibition of apoptosis. In summary, despite the distinct activation of inflammatory and oxidative stress pathways, both radiation alone and combined injury activated protective mechanisms such as HO-1 and AKT1, offering insights into molecular events before manifesting renal dysfunction.

Background: Our study investigates the prevalence and causes of injuries among undergraduate dental students during clinical sessions. Methods: The study was conducted at the Department of Dentistry, National and Kapodistrian University of Athens, focusing on injuries reported from 2021 to 2024. Data were collected through self-reported questionnaires and clinical records. The primary variables assessed included the type of injury, the instrument involved, the clinical procedure being performed, and the immediate actions taken post-injury. Serological testing was conducted on both students and patients to assess the risk of bloodborne pathogen transmission. Results: The findings revealed a high prevalence of injuries, with needles being the most common cause, followed by burs and dental probes. The most frequent injury type was piercing, primarily affecting the fingers. Periodontal treatments, restorative procedures, and endodontic treatments were the main activities leading to injuries. Despite normal medical records for most patients treated by injured students, serological testing showed significant positivity rates for HCV and HBV. It is noteworthy that most injured students demonstrated their commitment to safety by adhering to recommended post-exposure protocols, including wound cleaning, disinfecting, and serological testing. Our study highlights the critical need for enhanced biosafety awareness and training among dental students to reduce injury risks. Conclusions: These findings underline the necessity for integrated safety protocols and continuous education to improve clinical practices and ensure student safety.

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

Stress is an inherent sensation of being unable to handle demands and occurrences. If not properly managed, stress can develop into a chronic condition, leading to the onset of additional chronic health issues like cardiovascular illnesses and diabetes. Various stress meters have been suggested in the past, along with diverse approaches for its estimate. However, in the case of more serious health issues such as hypertension and diabetes, the results can be significantly improved. This study presents the design and implementation of a distributed wearable sensor computing platform with multiple channels. The platform aims to estimate stress levels in diabetes patients by utilizing a fuzzy logic algorithm that is based on the assessment of several physiological indicators. Additionally, a mobile application was created to monitor users' stress levels and integrate data on their blood pressure and blood glucose levels. Validation experiments were performed on patients with chronic diabetes, and the initial findings are presented in the study.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs), could be due to the magnified downstream effects initiated by a smaller group of genomic higher order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNA’s, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs/SNPs) and small insertions/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports, and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point, (the ‘fragilome’ and associated features), activated by a central mechanism (‘stress’) for studying NPD genetics, has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity and the association with certain other medical disorders.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

This study proposed to use wearable EEG to study the impact of vipassana mindfulness practice on beginner's physiological and neurological responses. Mindfulness meditation has been shown to have numerous benefits, including stress reduction, improved attention and cognitive function, and enhanced emotional regulation. The roots of mindfulness meditation in Buddhism emphasize cultivating present-moment awareness and insight. However, the neural mechanisms together with physiological mechanism and their interaction underlying these benefits remain poorly understood. Method: One middle age man (50 years old) participated in this longitudinal study using wearable EEG to investigate the neurophysiological change during a one-month consecutive vipassana mindfulness practice. Both EEG and heart rate responses were recorded each time, before (5 minutes), during (20 minutes), and after (5 minutes) meditation sessions. The EEG and HR data were analyzed by Matlab and EEGlab to examine changes in brainwave activity and heart rate. Results: alpha peak frequency (APF) is significantly lower after mindfulness meditation, as shown by comparison of APF before mindfulness (pre-5) and during mindfulness practice (med-20), and comparison between APF of pre-5 and after mindfulness practice (post-5). The same is with the beta peak power. While for theta peak frequency, it is significant lower during mindfulness meditation (med-20), when comparing to either pre-5 or post-5. See figure 1a. However, peak power index is not so sensitive, and it is more obvious in theta wave band. That is, the theta power peak is significantly lower after meditation, as can be observed in comparison between pre-5 and med-20, also between pre-5 and med-20. See figure 1b. STATE Heart-mean (bpm) Heart-std(bmp) pre-5 69.88 3.88 med-20 68.36 2.81 post-5 69.55 4.13 t-value test (pre-med) 0.0694 0.0003 t-value test (pre-post) 0.7934 0.3656 t-value test (post-med) 0.3193 0.0001 Table 1. The difference of Heart rate (mean and SD) in before (pre-5), during (med-20) and after (post-5)mindfulness meditation. We find significant change in standard deviation (SD) of heart rate between meditation and non-meditation mental states, as shown in table 1. The study provides insights into the underlying neurophysiological mechanisms of mindfulness meditation using wearable EEG devices. It demonstrates that in term of EEG measurement, spectrum frequency can be more sensitive than spectrum power; also heart rate variability as measured by SD is more sensitive to mean of HR. The proposed study contributes to the literature by using wearable EEG devices to collect data in a more accessible and convenient manner.

This work aimed to identify chemical compounds of Cinnamomum burmannii leaf essential oil (CBLEO) and to unravel antibacterial mechanism of CBLEO at molecular level for developing antimicrobial. CBLEO had 37 volatile profiling with abundant borneol (28.40 %), and showed good potential to control foodborne pathogens, of which Staphylococcus aureus had the greatest inhibition zone diameter (28.72 nm) with the lowest values of minimum inhibitory concentration (1.0 μg/mL) and bactericidal concentration (2.0 μg/mL). To unravel antibacterial action of CBLEO on S. aureus, a dynamic exploration of antibacterial growth, material leakage, ROS formation, protein oxidation, cell morphology and interaction with genome DNA were conducted on S. aureus exposed to CBLEO at different doses (1/2-2×MIC) and times (0-24 h), indicating that CBLEO acts as inducer for ROS production and oxidative stress of S. aureus. To highlight antibacterial action of CBLEO on S. aureus at molecular level, a comparative association of ROS accumulation with some key virulence-related gene (sigB/agrA/sarA/icaA/cidA/rsbU) transcription, protease production and biofilm formation in S. aureus subjected to CBLEO at different levels and times, revealing that CBLEO-induced oxidative stress caused transcript suppression of virulence regulators (RsbU and SigB) and its targeted genes, causing protease level increase destined for biofilm formation and growth inhibition of S. aureus, which may be as key bactericidal action. Our findings provide valuable information for studying the antibacterial mechanism of essential oil against pathogens.

(1) Background: The chemotherapeutic drug cisplatin exerts toxic side effects causing acute kidney injury. Mesenchymal stromal cells can ameliorate cisplatin-induced kidney injury. We hypothe-size that the MSC secretome orchestrates the vicious cycle of injury and inflammation by acting on proximal tubule epithelial cells (PTECs) and macrophages individually, but further by coun-teracting their cellular crosstalk. (2) Methods: Conditioned medium (CM) from adipose stromal cells was used, first assessing its effect on cisplatin injury in PTECs. Second, effects of cisplatin and CM on macrophages were measured. Lastly, in an indirect co-culture system the interplay between the two cell types was assessed. (3) Results: First, CM rescued PTECs from cisplatin-induced apoptosis by reducing oxidative stress and expression of nephrotoxicity genes. Second, while cisplatin exerted only minor effects on macrophages, CM skewed macrophage phenotypes to the anti-inflammatory M2-like phenotype and increased phagocytosis. Finally, in the co-culture system, CM suppressed PTEC death by inhibiting apoptosis and nuclei fragmentation. CM lowered TNF-α release. While cisplatin inhibited macrophage phagocytosis, PTECs, and CM to a greater extent, enhanced it. CM strongly dampened the inflammatory macrophage cytokine secretion triggered by PTECs. (4) Conclusion: ASC-CM surpasses the PTEC-macrophage cross-talk in cisplatin injury. The positive effects on reducing cisplatin cytotoxicity, on polarizing mac-rophages and on fine-tuning cytokine secretion underscores MSCs CM benefit to prevent kidney injury progression.

Diamond-like carbon (DLC) films have a promising tribological application in green precision manufacturing, but their toughness represents a serious issue in the way of their application perspective. The film thickness is on the micrometer scale and makes conventional methods unsuitable for its toughness characterization. The absence of an accepted method for characterizing the DLC toughness has hindered the related research on the development of toughening methods and understanding the mechanism. This work intends to explore a relatively simple and acceptable characterization method to measure the film toughness. Moreover, toughening mechanisms of DLC films are proposed during the characterization to reveal the toughening mechanism. The toughness can be fully characterized through combining impact toughness and scratch toughness. The impact toughness can be obtained by observing the size of the indentation and the crack state around the indentation in the impact experiment. The scratch toughness could be assessed by combining the scratch morphology and Crack Propagation Resistance (CPRS). The improvement of film toughness should be carried out from two aspects: preventing microcrack initiation and suppressing crack propagation. Appropriate doping of non-carbide metal particles can effectively improve the toughness of the film, and there are seven main factors affecting the toughening of the film. Five toughening mechanisms of non-carbide metals from film preparation to test stage are revealed during the investigation of the change patterns.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress has a severe effect on low-density lipoprotein (LDL) oxidation, leading to several detrimental health effects. Thereof, in this study, the effect of beeswax alcohol (BWA) was evaluated to prevent LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipoprotein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle and older human subjects (n=50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 μM), which was significantly better them the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails CuSO4 (final 0.5 μM) evoked LDL/apo-B oxidation and a marked reduction of lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counter carboxymethyllysine (CML, 500 ng) induced toxicity and rescued zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blind, placebo-controlled preliminary clinical study on middle and older-aged human subjects (n=50) exhibited that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA), total hydroperoxides, and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in anthropometric profile, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and has a positive impact on the oxidative variables of human subjects.

Despite great interest in how dynamic fluctuations in psychological states such as mood, social safety, energy, present-focused attention, and burnout impact stress, well-being, and health, most studies examining these constructs use retrospective assessments. Here, we discuss how ecological momentary assessments (EMAs) address methodological issues associated with retrospective reports, able to reveal dynamic associations between psychological states at small timescales that are often missed in stress and health research. In addition to helping researchers characterize daily and within-day fluctuations and temporal dynamics between different health-relevant processes, EMAs can elucidate mechanisms through which interventions reduce stress and enhance well-being. EMAs can also be used to identify changes that precede critical health events, which can in turn be used to inform the delivery of ecological momentary interventions (EMIs of just-in-time interventions) that prevent such events from occurring. To enable this work, this narrative review provides examples of scales and single-item questions used in EMA studies, makes concrete recommendations for researchers seeking to employ EMAs in their research, and discusses limitations of EMA methods. In doing so, we aim to encourage the use of these methods in research given that, when used carefully, EMA methods are well-poised to greatly advance our understanding of how intrapersonal dynamics affect stress levels, well-being, and human health.

The clinical relationship between diabetes and inflammation is well-established. Various branches of science independently have confirmed that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with Type 2 diabetes mellitus (T2DM). Under diabetic condition, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress and tissue damage are believed to have a role in the development of diabetes. Although the exact mechanism underlying the oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in onset and progression of vascular disease, kidney disease, hepatic injury, pancreas damage and, therefore holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications therapy fails to achieve the normal range for glycated hemoglobin target, signifying treatment resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical in vivo and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision of the future diabetes clinical trials.

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries [1]. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease [1], all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under transcriptional regulation of both the nuclear and the mitochondrial genome, to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, to dynamics which regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function to cause disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs including the ovary (oocyte and granulosa cell), uterus, placenta, and circulation to cause reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in transgenerational transmission of PCOS and metabolic disorders.

Oxidative stress-mediated damage is often a downstream result of Parkinson’s disease (PD), which is marked by sharp decline in dopaminergic neurons within the nigrostriatal regions of the brain, accounting for the symptomatic motor deficits in patients. Regulating the level of oxidative stress may present a beneficial approach in preventing PD pathology. Here, we assessed the efficacy of a nicotinamide adenine phosphate (NADPH) oxidase (NOX) inhibitor, an exogenous reactive oxygen species (ROS) regulator synthesized by Aptabio therapeutics with the specificity to NOX-1, 2, and 4. Utilizing N27 rat dopaminergic cells and C57Bl/6 mice, we confirmed that the exposures of alpha-synuclein preformed fibrils (PFF) induced protein aggregation, a hallmark in PD pathology. In vitro assessment of the novel compound revealed an increase in cell viability and decreases in cytotoxicity, ROS, and protein aggregation (Thioflavin-T stain) against PFF exposure at the optimal concentration of 10nM. Concomitantly, the oral treatment alleviated motor deficits in behavioral tests, such as hindlimb clasping, rotarod, pole, nesting, and grooming test, via reducing protein aggregation, based on rescued dopaminergic neuronal loss. The suppression of NOX-1, 2, and 4 within the striatum and ventral midbrain regions including SNc contributed to neuroprotective/recovery effects, making it a potential therapeutic option for PD.

Based on the Generalized bracket, or Beris-Edwards, formalism of non-equilibrium thermodynamics, we have recently proposed [Stephanou et al. Materials, 13, 2867 (2020)] a new differential constitutive model for the rheology of entangled polymer melts and solutions. It has amended the shortcomings of a previous model that was too strict in the values of the convective constraint release parameter for the model not to violate the second law of thermodynamics and has been shown capable of predicting a transient stress undershoot (following the overshoot) at high shear rates. In this work, we wish to further examine this model’s capability of predicting the rheological response of industrial polymer systems by extending it to its multiple-mode version. The comparison against industrial rheological data (High-Density Polyethylene resins), as compared against available experimental data in (a) Small Amplitude Oscillatory shear, (b) start-up shear, and (c) start-up uniaxial elongation, is noted to be good.

Background: Student-specific stress is pervasive and impairs health and attainment. Experimentally induced self-affirmation can reduce stress, but little is known about the mechanisms underlying this effect, and the role of individual differences. The present study explores the relationship between spontaneous self-affirmation, student-specific stress, and overlapping constructs of positive self-regard during the COVID-19 pandemic. Methods: The study investigated inter-relationships between spontaneous self-affirmation, student-specific perceived stress and potential covariates including self-esteem, self-integrity and habitual positive self-thought. University students (N = 151) aged 18 to 50 responded to an online questionnaire including the Spontaneous Self-Affirmation Measure, College Student Stress Scale, Rosenberg Self-Esteem Scale, Habitual Index of Positive Thinking and Self-Integrity Scale. Results: Unexpectedly, regression analysis revealed that spontaneous self-affirmation was a positive predictor of student-specific stress, seemingly driven by relational affirmations. Self-esteem and habitual self-thought were negative predictors of student-specific stress, whilst self-integrity was not a predictor. Conclusions: Habitual positive self-thought may offer a sustainable solution to student-specific stress, but spontaneous self-affirmation does not. A reduction in defensive responses, elicitation of negative emotions, or use of conditional relationships in relational affirmation

Dysfunction of the retinal pigment epithelium (RPE) is associated with several diseases characterized by retinal degeneration, such as diabetic retinopathy (DR). However, it has recently been proposed that outer retinal neurons also participate in the damage triggering. Therefore, we have evaluated possible crosstalk between RPE and photoreceptors in priming and maintaining oxi-dative damage of the RPE. For this purpose, we used ARPE-19 cells as a model of human RPE, grown in normal (NG, 5.6 mM) or high glucose (HG, 25 mM), and unoxidized (UOx) or oxidized (Ox) mammalian retinal rod outer segments (OS). ARPE-19 cells were efficient at phagocytizing rod OS in both NG and HG settings. However, in HG, ARPE-19 cells treated with Ox-rod OS accumulated MDA and lipofuscins and displayed altered LC3, GRP78, and Caspase 8 expression, compared to untreated and UOx-rod OS-treated cells. Data suggest that early oxidative damage may originate from the photoreceptors and subsequently extend to the RPE, providing a new perspective to the idea that retinal degeneration depends solely on a redox alteration of the RPE.

Many techniques have been and are being made to find alternatives to water-saving practices. Among them, Partial root drying (PRD), one of the effective approaches, plays a major role in reducing the harmful effects of water deficit stress. An experiment was carried out using irrigation strategies [I1 (100% full irrigation “FI”), I2 (75%FI), I3 (50%FI), and I4 (PRD (50%FI)] and soil organic mulch [L0 (Zero layer organic soil mulch” control”), L1 (Single layer organic soil mulch), L2 (Two layers of organic soil mulch), and L3 (Three layers of organic soil mulch)] to inspect the impact of those treatments for increasing yield, water productivity and saving energy under arid region conditions. To meet the study's objective, two field experiments were carried out at a private farm. Our results demonstrated a general decrease in water stress and salt accumulation inside root-zone area with PRD with L3. The PRD strategy increased fruit yields by 3.7 and 7.3% and water productivity by 51.9 and 53.1% compared with I1 during 2020/2021 and 2021/2022, respectively, while reducing the applied irrigation water by 50 %. The PRD strategy showed superior results in increasing mango yield and water productivity. In general, PRD can be used as good technique to save water and energy up to 50% and enhance productivity along with using organic mulching, ultimately improving mango yield under arid climatic regions. It may prove a good adaptation strategy for current and future water shortage scenarios of climate change.

This study investigates the stress corrosion cracking (SCC) behavior of type 316L stainless steel (SS316L) produced with sinter-based material extrusion additive manufacturing (AM). This technology has been shown to produce SS316L with microstructures and mechanical properties comparable to its wrought counterpart in the annealed condition. However, despite plenty of research on SCC of SS316L, little is known about SCC in sinter-based AM SS316L. This study focuses on the influence of sintered microstructures on susceptibility to SCC initiation and crack-branching. Custom-made C-rings were exposed to different stress levels in acidic chloride solutions at various temperatures. To better understand the SCC behavior of SS316L, solution-annealed (SA) and cold-drawn (CD) wrought SS316L were tested for comparison. Results showed that sinter-based AM SS316L was more susceptible to SCC initiation than SA wrought SS316L but more resistant than CD wrought SS316L. Moreover, sinter-based AM SS316L showed noticeably better resistance to crack-branching than both wrought SS316L counterparts. The investigation was supported by comprehensive pre- and post-test microanalysis using light optical microscopy (LOM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and micro-computed tomography (micro-CT)

(1) Background: The issue of human adaptation to the Arctic environmental factors is relevant. The adaptation can be assessed through dynamic monitoring of the functional state of a person during his/her stay there. The vitamin D level in blood is one of the markers of the functional reserves of the human body and can contribute to more successful adaptation in the Arctic. (2) Methods: The study involved 38 participants in the scientific and educational expeditionary project "Arctic Floating University-2021". Blood collection for determination of vitamin D content was carried out at the beginning of the expedition. A dynamic study was carried out for 20 days in the morning and in the evening during a marine scientific expedition to the Arctic. The main parameters of the functional state of the participants were assessed using instrumental psychophysiological, projective and questionnaire methods. Statistical methods: Mann-Whitney U-test, correlation analysis using the Spearman coefficient. (3) Results: It was found that at the beginning of the expedition, the functional state of participants with severe vitamin D deficiency is characterized by a shorter average duration of RR intervals and reduced SDNN values, which may indicate a higher level of regulatory mechanisms tension. The pronounced differences in the nature of the dynamic series of objective and projective working capacity parameters were manifested most clearly. According to the subjective questionnaire characteristics of well-being, activity and mood, no significant features of the participants with vitamin D deficiency were revealed. (4) Conclusion: The participants with vitamin D deficiency in blood are characterized by a reduced adaptive capacity during the expedition to the Arctic.

This study provides, to our knowledge, the first detailed analysis of how surface oil modifies air-sea interaction in a two-way coupled model, i.e., the coupled-ocean-atmosphere-wave-sediment-transport (COAWST) model modified to account for oil-related changes to air-sea fluxes. This study investigates the effects of oil on surface roughness, surface wind, surface and near surface temperature differences, and boundary-layer stability, and how those conditions ultimately affect surface stress. We first conducted twin coupled modeling simulations with and without the influence of oil over the Deepwater Horizon (DWH) oil spill period (April 21 to May 5, 2010) in the Gulf of Mexico. Then we compared the results by using a modularized flux model with parameterizations selected to match those selected in the coupled model adapted to either ignore or account for different atmospheric/oceanic processes in calculating surface stress. When non-oil inputs to the bulk formula treated as unchanged by oil, the surface stress changes are always negative due to oil-related damping of surface roughness alone. However, the oil-related changes to 10-m wind speed and boundary-layer stability are found to play a dominant role in surface stress changes relative to those due to the oil-related surface roughness changes, highlighting that most of the changes in surface stress are due to the oil-related changes in wind speed and boundary-layer stability. Finally, the oil-related changes to surface stress due to the combined oil-related changes in surface roughness, surface wind, and boundary-layer stability are not large enough to have a major impact on the surface current and surface oil transport, indicating that the feedbacks from the surface oil to the surface oil movement itself are minor for forecasting the surface oil transport unless the fractional oil coverage is much larger than found in this study.

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that occurs following exposure to traumatic events. The prevalence of PTSD is estimated to be 5-10% worldwide, and it is associated with significant distress and disability. Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer’s dementia and Parkinson’s disease. Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. In the current review, the PubMed and Scopus databases were searched for studies aimed at identifying genetic, biochemical, neuroimaging or behavioral markers associated with neurodegeneration in patients with PTSD. Out of a total of 342 citations retrieved, 29 relevant studies were identified for inclusion in the review. The results of these studies suggest that several potentially relevant biological markers, including cerebral cortical thinning, disrupted white matter integrity, specific genetic polymorphisms, immune-inflammatory alterations, vitamin D deficiency, metabolic syndrome and parasomnias, may be associated with an increased risk of neurodegeneration in patients with PTSD. Though many of these results need replication, they highlight a number of biological pathways that plausibly link PTSD with neurodegenerative disorders, and suggest potentially valuable avenues for prevention and early intervention in this patient population.

Background: Our study aimed to examine how modulating variables such as social support, health anxiety, coping, gender, being separated from home, and lockdown can modify or amplify the effect of perceived stress as a starting variable in the point of view of the output variable, dissociation. Methods: A cross-sectional survey was conducted in online form at two points in time: the beginning and the later stage of the COVID-19 pandemic. Results: We received a total of 1711 responses. Perceived stress moderately correlated with dissociation in both International and Hungarian samples. Health anxiety showed a strong direct and indirect correlation with dissociation. Regarding social support, the support of family significantly decreased the dissociative experiences in the Hungarian sample through mediating the stress and directly as well. In the international sample, the goal-oriented coping strategy had a strong decreasing effect on all dissociation scales in the first measurement, through mediation of perceived stress. As to the Hungarian sample, positive thinking was found to decrease dissociation through decreasing perceived stress. Conclusion: The cause and effect relationship between stress and dissociation may be tinctured by health anxiety, coping and social support, influencing dissociacion directly and indirectly. Social support, mainly support of the family and problem-focused coping strategies seem to alleviate dissociation-provoking effect of stress.

The work is devoted to the search for effective solutions to the applied problem of early diagnostics of plant stress in the conditions of smart farming and based on modern explicable artificial intelligence (XAI). The study mostly oriented on the theory and practice of XAI, focused on the use of hyperspectral imagery (HSI) and Thermal Infra-Red (TIR) sensor data at the input of a neural network. The first our goal is to build an XAI neural network, explainable due to its structure, the input of which is a datascientist oriented HSI 'explanator', and the output is a biologist oriented TIR 'explanator'. In the middle is SLP-regressor which solves the universal problem of training HSI pixels to temperatures of plants, needed for early plant stress diagnostic. The result can be considered as prototype of a special XAI explanator which is assigned to transform explanator specialized on area 1 onto explanator specialized on area 2. Using this HSI-TIR explanator we ensured the follows: extend HSI data by TIR attribute; providing TIR data for early diagnostic of plant stress; reducing dimensionality HSI needed for TIR training 25 times (from 204 to 8) preserving the same accuracy of temperature prediction (RMSE=0.2-0.3C). This reducing was achieved without using PCA methods. The constructed model is computationally efficient in training: the average training time is significantly less then 1 min (Intel Core i3-8130U, 2.2 GHz, 4 cores, 4 GB). One of the 8 channels, 820 nm, is the leader in correlation with TIR, what allows building local linear temperature prediction functions.

Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.

In this study, we surveyed over 600 participants to determine: a) major causes to mental stress during the pandemic and its future impacts, and b) diversity in public perception and acceptance (specifically for children) of Covid-19 vaccination. Statistical results and intelligent clustering outcomes indicate significant relationships between sociodemographic diversity, mental stress causes, vaccination perception, and Covid-19 infections. For instance, statistical results indicate significant dependence between mental stress due to Covid-19 and gender (p = 1.7e-05). Over 25% of males indicated work related stress comparing 35% in females however, females indicated more stressed (17%) due to relationships comparing to males (12%). Around 30% of Asian/Arabic participants don’t feel vaccination being safe as compared to 8% of white-British and 22% of white-European indicating significant dependence (p = 1.8e-08) with ethnicity. More specifically, vaccination acceptance for children is significantly dependent to ethnicity (p = 3.7e-05) where only 47% participants show willingness towards children’s vaccination. Primary dataset in this study along with experimental outcomes identifying sociodemographic information diversity with respect to public perception and acceptance of vaccination to children and potential stress factors might be useful for public and policy makers to be better prepared for future epidemics as well as working globally to combat mental health issues and running more effective vaccination campaigns.

Background: The demand in the development of cancer nanomedicine has increased due to various limitations in conventional cancer therapy. This study assessed the mRNA transcriptomic profiling of human HepG2 cells exposed to C. roseus-AgNPs. Methods: The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with C. roseus‑AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, DEG analysis, GO analysis, and pathway analysis. Results: The mean IC₅₀ values of C. roseus‑AgNPs on HepG2 was 4.38±1.59 µg/mL while on THLE3 cells was 800±1.55 µg/mL. Transciptomic profiling revealed an alteration of 296 genes. C. roseus‑AgNPs induced the expression of stress-associated genes such as MT, HSP and HMOX-1. Cellular signaling pathways were potentially activated through MAPK, TNF and TGF pathways that responsible for apoptosis and cell cycle arrest. The alteration of ARF6, EHD2, FGFR3, RhoA, EEA1, VPS28, VPS25, TSG101 indicated the uptake of C. roseus-AgNPs via both clathrin-dependent and clathrin-independent endocytosis. Conclusions: This study provides the new insights on gene expression study of biosynthesized AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicates the C. roseus‑AgNPs as an ideal anticancer candidate.

Creep deformation behaviour in single phase γ-TiAl alloy has been an extensively studied topic since the late 1970s. A lot of literatures have reported creep behaviour of γ-TiAl alloys, manufactured using different processing techniques [1]–[7]. The present discussion revisits the original work on understanding the tensile creep deformation behaviour of wrought single-phase γ-TiAl alloy by Hayes et al. [8] and is aimed to develop an understanding of steady state creep, through strain vs strain rate and strain vs ln(strain rate) plots. Besides, it also attempts to study the variation of stress exponent with temperature between 760-900⁰C and also, to determine activation energies using the two most common approaches, namely: Zener-Hollomon (Z-H) [9] and Sherby-Dorn (S-D, temperature compensated time approach) [10] for stress levels of 69 and 103.4 MPa between 760-900⁰C.

Keywords: underground engineering; numerical simulation; excavation length effect, major principal stress; displacement; damage initiation; CPU time

Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed subcellular fractionation of the brain from transgenic mice overexpressing the Q331K mutated TARDBP, and we analyzed REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of image analyses. TDP-43 aggregation was associated with alteration in mRNA levels of REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Further, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

Leaf mechanical wounding triggers a rapid, within minutes, release of a blend of volatile organic compounds (VOCs). Wounding-induced VOC blend is mainly composed of oxygenated ubiquitous stress volatiles such as methanol and volatile products of lipoxygenase (LOX) pathway (mainly C5 and C6 alcohols and aldehydes and their derivatives), but also includes multiple minor VOCs that collectively act as infochemicals inducing defences in non-damaged plant leaves, neighbouring plants and attracting herbivore enemies. Till present, interspecific variability of the rate of induction and magnitude of wounding-induced emissions, and the extent to which plant structural traits and physiological activity alter these emissions are poorly known. Particularly scarce is the information of the induced emissions in tropical agricultural plant species despite their economic importance and large area of cultivation at regional to global scales. We chose five tropical crops with varying photosynthetic activity and leaf structural characteristics: Abelmoschus esculentus, Amaranthus cruentus, Amaranthus hybridus, Solanum aethiopicum and Telfairia occidentalis to characterize the kinetics and magnitude of wounding-induced emissions, hypothesizing that the induced emission response is greater and faster in physiologically more active species with greater photosynthetic activity than in less active species. Rapid highly repeatable leaf wounds (12-mm cuts) were generated by a within-leaf-chamber cutting knife. Wounding-induced VOC emissions were measured continuously with a proton-transfer reaction time-of-flight mass spectrometer and gas-chromatography mass spectrometry was used to separate isomers. Twenty-three ion VOCs and twelve terpenoid molecule structures were identified, whereas ubiquitous stress volatiles methanol (on average 40% of total emissions), hexenal (24%), and acetaldehyde (11%) were the main compounds across the species. Emissions of low-weight oxygenated compounds (LOC, 70% of total), and LOX products (29%) were positively correlated across species, but minor VOC components, monoterpenoids and benzenoids were negatively correlated with LOC and LOX, indicating a reverse relationship between signal specificity and strength. There was a large interspecific variability in the rate of induction and emission magnitude, but the hypothesis of a stronger emission response in physiologically more active species was only partly supported. In addition, the overall emission levels were somewhat lower with different emission blend compared to the data reported for wild species, as well as different shares for the VOCs in the blend. The study demonstrates that wounding-dependent emissions from tropical agricultural crops can significantly contribute to atmospheric volatiles, and these emissions cannot be predicted based on current evidence of wild plant model systems.

Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia’s oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow bioreactor. Mouthwash and gels containing DNA-RNA compounds and other bioactive molecules were tested on a model of oxidative stress generated by hydrogen peroxide treatment. Epithelia viability was evaluated using a biochemical MTT-based assay and confocal microscopy; structural and ultrastructural morphology was evaluated by light microscopy and TEM. Results: DNA-RNA showed non-cytotoxic activity and effectively protected against oxidative stress, but not in its prevention. Gel formulation did not express adequate activity compared to the mouthwash. Excipients played a fundamental role in enhancing or even decreasing the bioactive molecules’ effect. Conclusion: A mouthwash formulation with hydrolyzed DNA-RNA effectively protected against oxidative stress without additional enhancement by other bioactive molecules. Active compounds such as hyaluronic acid, β-Glucan, allantoin, bisabolol, ruscogenin, and essential oils showed a protective effect against oxidative stress, which was not synergistic with the one of DNA-RNA. Surfactant agents showed harmful activity against oral epithelia.

The effect of four soil-applied sulfur [S; 100 mg S kg-1 soil (100S) and 200 mg S kg-1 soil (200S)] in different sources (elemental S, ammonium sulfate, gypsum or magnesium sulfate) in protecting mustard (Brassica juncea L. Czern & Coss.) from cadmium effects was studied. Based on the observed reduction in growth and photosynthesis in plants subjected to 100 and 200 mg Cd kg-1 soil, B. juncea cv. Giriraj was selected as the most Cd-tolerant among five cultivars (namely, Giriraj, RH-0749, Pusa Agrani, RH-406, and Pusa Tarak). Sulfur applied to soil mitigated the negative impact of Cd on sulfur assimilation, cell viability and photosynthetic functions, with a lower lipid peroxidation, electrolyte leakage, and contents of reactive oxygen species (ROS: hydrogen peroxide, H2O2, and superoxide anion, O2•−). Generally, added S caused a higher activity of antioxidant enzymes (ascorbate peroxidase, catalase and superoxide dismutase), and contents of ascorbate (AsA) and reduced glutathione (GSH), and increases in the activities of their regenerating enzymes (dehydroascorbate reductase and GSH reductase), as well as rises in S assimilation, biosynthesis of non-protein thiols (NPTs) and phytochelatins (PCs). Compared to the other S-sources tested, elemental S more prominently protected B. juncea cv. Giriraj against Cd-impacts by minimizing Cd-accumulation and its root-to-shoot translocation; decreasing cellular ROS and membrane damage, and improving Cd-chelation (NPTs and PCs), so strengthening the defense machinery against Cd. The results suggest the use of elemental S for favoring the growth and development of cultivated plants also in Cd-contaminated agricultural soils.

Background: The primary objective worldwide during the COVID-19 pandemic has been controlling disease transmission. However, lockdown measures used to mitigate transmission have affected human behavior and altered lifestyles, with a likely impact on chronic non-communicable diseases. More than a year into the pandemic, substantial peer-reviewed literature has emerged on altered lifestyles following the varying lockdown measures imposed globally to control the virus spread. Objective: To explore the impact of lockdown measures on the six lifestyle factors, namely diet, physical activity, sleep, stress, social connectedness, and the use of tobacco, alcohol, or other harmful substances.Methods: We comprehensively searched PubMed and the World Health Organization’s global literature database on COVID-19 and retrieved 649 relevant articles for the narrative review. A critical interpretative synthesis of the articles was performed.Results: Most of the articles included in the review identified the negative effect of lockdown measures on each of the lifestyle factors in many parts of the world. Interestingly, encouraging lifestyle trends were also highlighted in a few articles. Such trends can positively influence the outcome of lifestyle-related chronic diseases, such as obesity and diabetes.Conclusions: The COVID-19 pandemic provides an opportunity to better understand the negative impact of strict lockdown measures on lifestyles. At the same time, it helps us identify and initiate positive behavioral changes, which, if consolidated, could improve chronic disease outcomes. It is up to governments, communities, and healthcare/academic entities to derive benefit from lessons learned from the pandemic, with the ultimate objective of better educating and promoting healthy lifestyles among communities.

Four decades of proteasome research have yielded extensive information on ubiquitin-dependent proteolysis. The archetype of proteasomes is a 20S barrel-shaped complex that does not rely on ubiquitin as a degradation signal but can degrade substrates with a considerable unstructured stretch. Since roughly half of all proteasomes in most eukaryotic cells are free 20S complexes, ubiquitin-independent protein degradation may coexist with ubiquitin-dependent degradation by the highly regulated 26S proteasome. This article reviews recent advances in our understanding of the biochemical and structural features that underlie the proteolytic mechanism of 20S proteasomes. The two outer α-rings of 20S proteasomes provide a number of potential docking sites for loosely folded polypeptides. The binding of a substrate can induce asymmetric conformational changes, trigger gate opening, and initiate its own degradation through a protease-driven translocation mechanism. Consequently, the substrate translocates through two additional narrow apertures augmented by the β-catalytic active sites. The overall pulling force through the two annuli results in a protease-like unfolding of the substrate and subsequent proteolysis in the catalytic chamber. Although both proteasomes contain identical β-catalytic active sites, the differential translocation mechanisms yield distinct peptide products. Non-overlapping substrate repertoires and product outcomes rationalize cohabitation of both proteasome complexes in cells.

Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by sensorineural deafness and motor neuron degeneration. Since riboflavin plays key functions in biological oxidation-reduction reactions, energy metabolism pathways involving flavoproteins are affected in RTD. We recently generated iPSC lines from affected individuals as an in vitro model of the disease and documented mitochondrial impairment in these cells dramatically impacting cell redox status. In the present work, we extend our study to motor neurons (MNs), i.e., the cell type mostly affected in patients with RTD. Altered intracellular distribution of mitochondria was detected by confocal microscopic analysis, following immunofluorescence for superoxide dismutase 2 (SOD2), as a dual mitochondrial and antioxidant marker, and βIII Tubulin, as neuronal marker. We demonstrate significantly lower SOD2 levels in RTD MNs, as compared to their healthy counterparts. Mitochondrial ultrastructural abnormalities were also assessed by Focused Ion Beam/Scanning Electron Microscopy. Moreover, we investigated the effects of combination treatment using riboflavin and N-acetylcysteine, which is a widely employed antioxidant. Overall, our findings further support the potential of patient specific RTD models, and provide evidence of mitochondrial alterations in RTD-related iPSC-derived MNs, emphasizing oxidative stress involvement in this rare disease. We also provide new clues for possible therapeutic strategies, aimed at correcting mitochondrial defects, based on the use of antioxidants.

The review analyzes a possible role of autoimmune processes in the pathogenesis of schizophrenia and evolution of concepts on this issue from its origin to present. Risks of autoimmune processes causing schizophrenia are associated with several factors: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway disorder with overproduction of quinolinic, anthranilic and kynurenic acids (possibly altering both neurons and T-regulators), increased intestinal permeability, as well as food antigens’ effects, stress and infections with various pathogens at different stages of ontogenesis. An increase in the levels of proinflammatory cytokines and chemokines as well as a decrease in the levels of anti-inflammatory ones also may contribute to schizophrenia risks. Schizophrenia often occurs in those patients having various autoimmune diseases and their first-degree relatives. Cases of schizophrenia resulted from autoimmune pathogenesis (including autoimmune encephalitis caused by autoantibodies against various neuronal antigens) are characterized by quite severe cognitive and psychotic symptoms and less favorable prognosis. This severe course may result from the chronic immune damage of the neuronal receptors such as NMDA, GABA, and others and depend on hyperprolactinemia, induced by antipsychotics, but aggravating autoimmune processes [with 2 tables, 4 figures, bibliography: 99 references].

Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules.

Manganosalen complexes are coordination compounds that possess a chelating salen-type ligand, a class of bis-Schiff bases obtained by condensation of salicylaldehyde and a diamine. They may act as catalytic antioxidants mimicking both the structure and the reactivity of the native antioxidant enzymes active site. Thus, manganosalen complexes have shown to exhibit superoxide dismutase, catalase, and glutathione peroxidase activities, and they could potentially facilitate the scavenging of excess ROS, thereby restoring the redox balance in the damaged cells and organs. Initial catalytic studies compared the potency of these compounds as antioxidants in terms of rate constants of the chemical reactivity against ROS, giving catalytic values approaching and even exceeding that of the native antioxidative enzymes. Although most of these catalytic studies lack of biological relevance, subsequent in vitro studies have confirmed the efficiency of many manganosalen complexes in oxidative stress models. These synthetic catalytic scavengers, cheaper than natural antioxidants, have accordingly attracted intensive attention for the therapy of ROS-mediated injuries. The aim of this review is to focus on in vivo studies performed on manganosalen complexes and their activity on the treatment of several pathological disorders associated with oxidative damage. This disorders, ranging from the prevention of fetal malformations to the extension of lifespan, include neurodegenerative, inflammatory and cardiovascular diseases, tissue injury, and other damages related to liver, kidney or lungs.

The Hertzian contact theory, as well as most of the other classical theories of normal and tangential contact, provides displacements and the distribution of normal and tangential stress components directly in the contact surface. However, other components of the full stress tensor in the material may essentially influence the material behaviour in contact. Of particular interest are principal stresses and the equivalent von Mises stress, as well as the gradient of the hydrostatic pressure. For many engineering and biomechanical problems, it would be important to find these stress characteristics at least in the contact plane. In the present paper, we show that the complete stress state in the contact plane can be easily found for axially symmetric contacts under very general assumptions. We provide simple explicit equations for all stress components and the normal component of the gradient of hydrostatic pressure in the form of one-dimensional integrals.

In the author's opinion, many global problems that face humanity - in the fields of education, medicine, management etc can be tackled more effectively if the cyclic nature of self-reproducing systems – including living beings – is taken into account. Summarizing the main physiological findings of the last decades on "adaptation reactions", one can very roughly say that the way of action which is effective in the sense of productive activity of people happens at the same time to be healthy, and it gives the participants of the process the feeling of happiness. The present paper represents a very short overview of the contemporary concepts of the adaptation reactions based on the fundamental understanding of their cyclic nature due to general properties of self-reproducing systems. One interesting feature of self-reproduction cycles is its first "phase of orientation" which was not discussed in detail in the past but plays a key role in the whole cycle.

According to the recent data, nitric oxide (NO) is a chemical messenger that mediates functions such as vasodilation and neurotransmission, it also possesses antimicrobial and antitumoral activities. Nitric oxide has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. We searched for full-text English publications in Pubmed and SNPedia databases using keywords and combined word searches (nitric oxide, single nucleotide variants, single nucleotide polymorphisms, genes) over the past 15 years. In addition, earlier publications of historical interest were included in the review. In our review, we have sum up all NOS1, NOS2, NOS3, and NOS1AP single nucleotide variants (SNVs) involved in the development of mental disorders and neurological diseases/conditions. The results of studies we have discussed in this review are contradictory, that might be due to different designs of the studies, small sample sizes in some of them, as well as different social and geographical characteristics. However, the contribution of genetic and environmental factors has been understudied, that makes this issue increasing for researchers as the understanding of these mechanisms can support a search for new approaches to pathogenetic and disease-modifying treatment.

Shale gas reservoirs (SGR) are important replacements for conventional energy resources and have been widely exploited by hydraulic fracturing technologies. On the one hand, due to the inherent ultra-low permeability and porosity, there is stress sensitivity in the reservoirs generally. On the other hand, hydraulic fractures and the stimulated reservoir volume (SRV) generated by the massive hydraulic fracturing operation have contrast properties with the original reservoirs. These two phenomena bring huge challenges in SGR transient pressure analysis. Although some works in the literatures have been done on the transient pressure analysis of multi-fractured horizontal wells in SGR, unfortunately, none of them has taken the stress sensitivity and spatially varying permeability of SRV zone into consideration simultaneously. To fill this gap, this paper first idealizes the SGR to be four linear composite regions. What’s more, SRV zone is further divided into sub-sections on the basis of non-uniform distribution of proppant within SRV zone which easily yields spatially varying permeability away from the main hydraulic fracture. The stress sensitivity is characterized by the varying permeability depended on the pore pressure. By means of perturbation transformation and Laplace transformation, an analytical multi-linear flow model (MLFM) is obtained and validated by the comparison with the previous model. On the basis of our model, the flow regimes are identified and the sensitivity analysis of critical parameters are conducted to further understand the transient pressure behaviors. The research results provided by this work are of significance for well test interpretation and production performance analysis of SGR.

Rigid-hulled inflatable boats are extremely practical and popular nowadays. They offer a effective conciliation among usability and costs. Their stable and seaworthy behaviour is guaranteed by performing hydroplaning hulls coupled with unsinkable inflated tubes. At the same time, their design is often based on tradition and preconceptions. Rarely, the design assumptions are validated by the reality or, even, by deeper investigations. In this article, both numerical methods and experimental mechanics techniques are proposed as an essential way for supporting the designers in their decisive tasks. Three different situations are detailed where a numerical or an experimental approach shows its benefit inside the engineering design process: firstly permitting to investigate the behaviour of materials driving the fiberglass selection; then measuring the levels of stress and strain in the hull during sailing; finally, using all available information as a base for developing numerical models of the hull slamming in waves. Even if the discussion is focused on a rigid inflatable boat, large part of its considerations is relevant beyond this special case.

Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

1) This study describes the good evolution of a 6-year-old girl genetically diagnosed with Rett syndrome (RTT), after having been treated with IGF-1, MT (MT), blackcurrant extracts (BC), and rehabilitation during 6 months. 2) The patient stopped her normal development from the first year of age. The patient showed low weight and height and met the main criteria for typical RTT. Curiously, there was pubic hair (Tanner II), very high plasma testosterone, despite low gonadotropins. No adrenal enzymatic deficits existed, and ultrasound abdominal studies were normal. Treatment consisted in IGF-1 (0.04 mg/kg/day, 5/week, sc) during 3-months and then 15-days resting, MT (50 mg/day, orally, uninterruptedly) and neurorehabilitation. The new blood tests were absolutely normal and the pubic hair disappeared. Then, a new treatment with IGF-1, MT, and BC started for another 3 months. After it, pubic Tanner stage increased to III, without a known cause. 3) The treatment followed led to clear improvements in most of the initial impairments, perhaps because of the effect of IGF-I, the antioxidant effects of MT and BC, and the increase in cyclic-glycine-proline (cGP) after BC administration. 4) A continuous treatment with IGF-1, MT and BC may recover most of the neurologic disabilities that occur in RTT.

The workplace is an ideal setting for health promotion. The regular medical examination of workers enables us to screen for numerous diseases, spread good practices and correct lifestyles, and obtain a favourable risk/benefit ratio. The continuous monitoring of the level of workers' wellbeing using a holistic approach that goes beyond the simple prevention of occupational risks enables us to promptly identify problems in work organization and the company climate. Problems of this kind can be adequately managed by using a participatory approach. In this study participatory ergonomics groups were used to improve occupational life in a small company. After intervention we observed a reduction in levels of perceived occupational stress measured with the effort / reward imbalance model, and an improvement in psychological wellbeing assessed by means of the Goldberg anxiety / depression scale. Although the limited size of the sample calls for a cautious evaluation of this study, the GEP© strategy proved to be a useful tool due to its cost-effectiveness.

Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

Environmental darkness signal is transferred from the retina to the pineal gland triggering melatonin secretion. Melatonin influences the synthesis and release of the hypothalamic GnRH and the adenohypophyseal gonadotropin hormones and therefore, regulates testicular function in photoperiodic species. Besides the brain, direct actions of melatonin at the testicular level have also been described. Melatonin released from the pineal gland to the circulation is taken up by peripheral tissues including testes. Testicular synthesis of melatonin has also been reported. The two key somatic cell types in the testis, Leydig and Sertoli cells, express melatonergic receptors. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences the oxidation state and the energy metabolism, and consequently may regulate spermatogenesis. Melatonergic receptors were also described in testicular macrophages and mast cells of infertile patients. Whereas melatonin exerts anti-proliferative and anti-inflammatory effects on testicular macrophages, it provides protective effects against oxidative stress in testicular mast cells. These data pinpoints melatonin as a key player in the regulation of testicular physiology (i.e. steroidogenesis, spermatogenesis) mostly in seasonal breeders. More importantly, melatonin is also involved in the modulation of testicular inflammatory and oxidant/anti-oxidant states in patients with idiopathic infertility.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

In Alzheimer’s disease (AD), tau dissociates from microtubules (MTs) due to hyperphosphorylation and misfolded. It is degraded by various mechanisms, including the 20S proteasome, chaperone-mediated autophagy (CMA), 26S proteasome, macroautophagy, and aggrephagy. Neurofibrillary tangles (NFTs) form upon impairment of aggrephagy, and eventually, the ubiquitin chaperone valosin-containing protein (VCP) and heat shock 70 kDa protein (HSP70) are recruited to the sites of NFTs for extraction of tau for the ubiquitin-proteasome system (UPS)-mediated degradation. However, impairment of tau degradation in neurons allows tau to be secreted into the extracellular space. Secreted tau can be monomers, oligomers, and paired helical filaments (PHFs), which are seeding competent pathological tau that can be endocytosed/phagocytosed by healthy neurons, microglia, astrocytes, oligodendrocyte progenitor cells (OPCs) and oligodendrocytes, often causing proteotoxic stress, and eventually triggers senescence. Senescent cells secrete various senescence-associated secretory phenotype (SASP) factors, which trigger cellular atrophy, causing decreased brain volume in human AD. However, the molecular mechanisms of proteotoxic stress and cellular senescence are not entirely understood and are an emerging area of research. Therefore, this comprehensive review summarizes pertinent studies that provided evidence for the sequential tau degradation, failure, and the mechanistic link between tau-driven proteotoxic stress and cellular senescence in AD.

There are many features of homeostasis worth investigating such as how it works (information pathways, set point processing), where its command and control processors are located in the cell, the language used and how homeostasis interacts with all effectors (all aspects of an organism's functional maintenance and development such as cell differentiation). All are necessary and valid inquiries, but this paper examines the implications of ignoring it as a factor of disease causation. Alternatively when properly understood the homeostasis profile becomes a rational explanation for any individual’s range of health; where some areas are very resistant to disease (resilient) and other areas of homeostasis are dysfunctional leading to minor, moderate or very susceptible tendencies to disease (a lack of resilience in homeostasis). An understanding of this phenomenon, its interactions with gene expression (epigenetics) is necessary in order to evaluate the solutions for acute and chronic diseases. By this method diseases can be defined more precisely as specific susceptibilities in homeostasis, leading to a method to restore specific homeostasis functions.

In this work, we study a boundary control problem for the evolutionary Stokes equations, under mixed boundary conditions, in two and three dimensions. The Stokes equation is a valuable tool in cardiovascular biomechanics, especially for modeling blood flow in low-velocity and high-viscosity conditions. Its application in the microvasculature, the design of medical devices, and the study of cardiovascular diseases helps improve the understanding and treatment of various pathological conditions. We provide a comprehensive theoretical framework to address the analysis and the derivation of a system of first-order optimality conditions that characterizes the solution of the control problem. Finally, solution-finding algorithm is proposed and illustrated with some simulations.

Bacillus amyloliquefaciens GL18 has been proven to have good resistance ability and can promote the growth of Avena sativa cultivar ‘Qingyan 1’. Herein, Illumina high-throughput transcriptome sequencing technology was used to analyze the differential expression of genes between the interaction group (LB) and the control group (LCK) when ‘Qingyan 1’ roots interacted with GL18 bacterial suspension or sterile water for 12 h under 4 °C low-temperature stress. The gene function annotation information was obtained using Gene Ontology (GO) functional classification and enrichment analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and annotation of differentially expressed genes was used to explore the related signal transduction pathway of ‘Qingyan 1’ response to cold stress induced by Bacillus GL18. The results showed that after ‘Qingyan 1’ seedlings interacted with GL18 bacterial suspension or sterile water for 12 h, comparing the LB with the LCK or CK (the control group at 26 °C), there were 12,061 and 25,489 differentially expressed genes, respectively. Their functions were mainly related to metabolic process, cellular process, catalytic activity, binding, and cellular parts, and they were significantly enriched in plant tissue growth and development, cell wall, organelle membrane synthesis, thiamine and its compounds, biosynthesis, polyamine decomposition, and other metabolic processes. Signal transduction was detected through KEGG pathway enrichment analysis, and corresponding genes, such as AUXI, PP2C, SNRK2, ABF, BRI1, and PIF4, were expressed. The expression of genes directly involved in plant growth was upregulated in the presence of GL18, as shown by real-time quantitative PCR analysis. It was speculated that the normal growth and development of ‘Qingyan 1’ under low-temperature stress promoted by GL18 is a result of the integration of multiple pathways in terms of regulating endogenous hormone metabolism, secondary metabolite synthesis, and photosynthesis.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

This research evaluates the effect of varying hexagonal opening angles on the flexural and shear capacity of castellated beams. This study is conducted through experimental and numerical approaches using WF 150.75.5.7 steel profiles. The hexagonal opening angles are varied to 20°, 30°, 45°, 55°, and 60°. Experimental testing results show that beams with a 20° opening angle have higher flexural and shear capacities compared to larger opening angles. Numerical testing results are consistent with experimental results, showing more uniform deformation patterns and stress distribution at smaller opening angles. These findings contribute significantly to the design of more efficient and effective castellated beams in modern structural applications, particularly in constructions requiring high flexural and shear capacities.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

Obstructive sleep apnea (OSA) is a common sleep disorder that is associated with a wide variety of health conditions, including cardiovascular, cerebrovascular, metabolic, neoplastic, and neurocognitive manifestations. OSA as a chronic condition is mainly characterized by repeated upper airway obstructions during sleep that cause episodes of intermittent hypoxia (IH), resulting in tissue hypoxia-reoxygenation cycles. Decreased arterial oxygen pressure (PaO₂) and hemoglobin saturation (SatO₂) stimulate reflex responses to overcome the obstruction. The prevalence of OSA is significant worldwide, and an underrated problem when focusing on women during pregnancy. The physiological changes associated with pregnancy, especially during its latest stages, are related with a higher prevalence of OSA events in pregnant mothers, and associated with an increased risk of hypertension, pre-eclampsia and diabetes, among other deleterious consequences. Furthermore, OSA during pregnancy can interfere with normal fetal development and is associated with growth retardation, preterm birth, or low term weight. Carotid body overstimulation and hypoxia-reoxygenation episodes contribute to cardiovascular disease and oxidative stress, which can harm both mother and fetus and have long-lasting effects that can reach into adulthood. Because IH is the hallmark of OSA, this review examines the literature available about the impact of gestational intermittent hypoxia (GIH) on the respiratory system at maternal, fetal, and offspring levels. Offering the latest scientific data about OSA during pregnancy, we may help to tackle this condition with lifestyle changes and therapeutic approaches, that could influence the mothers, but also impact adult health problems, mostly unknown, inherited from these hypoxic episodes in the uterus.

One of the relevant goals in forging technologies is simplifying the existing process and developing new processes that can retain the original or very close to the original dimensions and billet shape after the end of the deformation cycle. This study attempts to develop a forging equipment design that provides alternating cyclic loading; the alternate cyclic forging (ACF) method is proposed. To preliminary evaluate the ACF and study the plastic deformation behavior, numerical simulation via finite element modeling (FEM) was conducted using DEFORM-3D. The main attention was paid to the metal flow characteristics, effective strain and stress distribution, and the forging load. The ACF results in non-uniform metal flow with the formation of diagonal and vortex flows were demonstrated. Maximum effective strains and stresses zones are localized at two points of the billet contact with the surface of the tooling container and at two points of the interface between the punches. It was also assumed that reducing the contact area between the punch and the billet using separate semi-cylindrical punches can reduce the forging load. Preliminary finite element analysis (FEA) results of the proposed process after four successive steps of the deformation cycle confirmed the feasibility of its general implementation.

Rice, a globally important food crop, faces significant challenges due to salt and drought stress. These abiotic stresses severely impact rice growth and yield, manifesting as reduced plant height, decreased tillering, reduced biomass, and poor leaf development. Recent advances in molecular biology and genomics have uncovered key physiological and molecular mechanisms that rice employs to cope with these stresses, including osmotic regulation, ion balance, antioxidant re-sponses, signal transduction, and gene expression regulation. Transcription factors such as DREB, NAC, and bZIP, as well as plant hormones like ABA and GA, have been identified as crucial reg-ulators. Utilizing CRISPR/Cas9 technology for gene editing holds promise for significantly en-hancing rice stress tolerance. Future research should integrate multi-omics approaches and smart agriculture technologies to develop rice varieties with enhanced stress resistance, ensuring food security and sustainable agriculture in the face of global environmental changes.

This study explored the effectiveness of a virtual music therapy program, based on positive psychotherapy principles, for college students during the COVID-19 pandemic. Twenty-four undergraduate students with partial PTSD were initially assigned to either an experimental group or a control group, with 11 participants in each group by the study's end. The experimental group underwent 15 video sessions of the therapy program, completing one session per weekday over three weeks. The program involved worksheets targeting goals aligned with positive psychology, such as positive affect, life meaning, personal strengths, gratitude, hope, and happiness. Activities included writing music autobiographies, creating and analyzing song lyrics, and exploring various music pieces. The effectiveness of the intervention was measured using the 21-item Depression Anxiety Stress Scale and the Korean Version of Positive Psychological Capital (K-PPC) before, immediately after, and three weeks post-program. The experimental group showed significant improvements in stress, anxiety, depression, self-efficacy, resilience, and the K-PPC total score compared to the control group. These improvements were maintained at the three-week follow-up. The findings suggest that positive psychology-based virtual music therapy can significantly enhance the mental health of highly stressed college students, especially during challenging times like the COVID-19 pandemic.

This study assessed the impact of inoculation with plant growth-promoting bacteria (PGPB) on stress-resistance and growth-promoting metabolites in Salicornia europaea L. across controlled and field conditions. Salicornia europaea seeds, inoculated with Brevibacterium casei EB3 and Pseudomonas oryzihabitans RL18, were grown in controlled laboratory experiments and in a nat-ural field setting. Metabolite composition was analyzed using GC-MS and UHPLC-MS. Under controlled conditions, PGPB inoculation significantly increased levels of unsaturated fatty acids, sugars, citric acid, acetic acid, chlorogenic acids, and quercetin. Inoculation under field condi-tions increased glucose, fructose, quercetin, and apigenin, alongside decreased unsaturated fatty acids and sterols, indicating a stress response shift in plant metabolism. Under controlled condi-tions, enhanced metabolite profiles induced by inoculation likely contributed to augmented bio-mass production and environmental stress resistance. Field plants revealed distinct phytochemi-cal profiles, suggesting higher stress levels. However, the accumulated metabolites from inocula-tion could enhance the plant's ability to cope with adverse conditions and improving stress tol-erance. This study unveils the intricate metabolic adaptations of Salicornia europaea under con-trolled and field stress conditions, highlighting PGPB's potential to enhance plant stress tolerance. Elevated stress-related metabolites may fortify plant defense mechanisms, laying the ground-work for stress-resistant crop development through PGPB-based inoculants, especially in saline agriculture.

The olive tree (Olea europaea L.) is an evergreen tree that occupies 19% of the woody crop area and is cultivated in 67 countries on five continents. The largest olive production is concentrated in the Mediterranean basin, where the olive tree has had an enormous economic, cultural and environmental impact since the 7th century BC. In the Mediterranean region, salinity stands out as one of the main abiotic stress factors significantly affecting agricultural production. Moreover, climate change is expected to lead to increased salinisation in this region, threatening olive productivity. Salt stress causes combined damage by osmotic stress and ionic toxicity, restricting olive growth and interfering with multiple metabolic processes. A large variability in salinity tolerance among olive cultivars has been described. This paper aims to synthesize information from the published literature on olive adaptations to salt stress and its importance in salinity tolerance. The morphological, physiological, biochemical, and molecular mechanisms of olive tolerance to salt stress are reviewed.

Obesity and environmental toxins are risk factors for breast cancer, however there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a biproduct in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and 0.7mM acrylamide-supplemented water or control water. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. Knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.