Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

This study evaluated the exogenous application of PGRs substitute chemical fertilization without compromising the growth and yield of tomato in fluctuated day-night temperature and humidity stressed late winter. Two-factor experiment comprising chemical fertilizers at 100, 110, 90 and 80 % of recommended doses besides control and PGRs of GA3; NAA, 4-CPA and SA @ 50 ppm including control was conducted where treatments were assigned in triplicates. Results revealed no significant variation among the fertilizer doses (80% to 110% of recommendation) regarding growth and yield contributing traits while among the PGRs, GA3 @ 50 ppm produced maximum number of flower clusters plant-1 (16.85), flowers (8.80) and fruits (5.79) cluster-1, single fruit weight (67.83 g) and fruit yield (6.61 kg plant-1) of tomato that was statistically identical with the findings of SA. But significant reduction in yield was noted in NAA and 4-CPA (1.20 kg and 1.21 kg plant-1, respectively). Interestingly, GA3 and SA in combination with any doses of the studied fertilizers maximize the tomato morphological and reproductive traits while fertilizer plus NAA and 4-CPA interaction gave the inferior results. Further, correlation matrix and PCA findings revealed that five fertilizer doses have no distinctiveness whereas GA3 and SA has distinct position than other PGRs with the maximum dependent variables those were contributed positively in the total variations. The study findings suggested that 20% fertilizer requirement could be reduced with the substitution of GA3 and SA @ 50 ppm for successful cultivation of tomato in late winter having the extreme environmental issues.

The effect of high temperature (HT) stress on nicotine biosynthesis in Nicotiana attenuata was examined. Nicotine content was measured in mature leaves, young sink leaves and in roots from well-watered plants grown at 25 °C as controls and from plants exposed to 38 °C and 43 °C temperatures applied for 24, 48, 72 and 96-hr duration. At 38 °C, all leaf nicotine levels were significantly less than control plants for up to 72-hr exposure but rose sharply thereafter to levels significantly greater than controls with 96-hr exposure. In contrast, plants exposed to 43 °C never exhibited a reduction in leaf nicotine content and showed a significant increase in content with just 48-hr exposure. When radioactive 11CO2 was administered to plants, HT stress significantly reduced fixation. Furthermore, radiocarbon flux analysis revealed that ‘new’ C partitioning (as 11C) into the [11C]-amino acid pool was significantly reduced with HT stress as were yields of [11C]-aspartic acid, an important amino acid in nicotine biosynthesis, and its beta-amido counterpart [11C]-asparagine significantly reduced. In contrast, [12C]-aspartic acid levels appeared unaffected at 38 °C but were significantly elevated at 43 °C relative to controls. Additionally, [12C]-asparagine levels were significantly elevated at both stress temperatures. Finally, leaf total soluble protein (TSP) was reduced 39% with long exposures to both stress temperatures. However, Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) which was 41% TSP appeared unaffected by HT stress. Altogether, these results support the theory that plant proteins other than Rubisco degrade at elevated temperatures freeing up essential amino acids supporting the nicotine biosynthetic machinery, and while feedback might downregulate de novo amino acid synthesis from ‘new’ C resources, more than likely plant C/N rebalancing caused by HT reductions in C input restricted N uptake, which in turn, limited this process.

Non-alcoholic steatohepatitis (NASH) is diagnosed by the occurrence of fat buildup, inflammation, and fibrotic changes within the liver. NASH has the capacity to proceed to the advancement of decompensated cirrhosis and carcinoma by inflammation and oxidative stress. Although Agrimonia pilosa has traditionally been used medicinal purposes, its effects on the liver remains incompletely elucidated. In this research, we assessed the therapeutic outcomes of Agrimonia pilosa extract (APE) on free fatty acid (FFA)-treated HepG2 cellular hepatic steatosis and in a choline-deficient, L-amino acid-defined, high-fat diet with 0.1% methionine (CDAHFD)-induced NASH mouse model. In FFA-treated cells, APE inhibited intracellular lipid accumulation, and regulated the mRNA and protein expressions of modulators of fatty acid (FA) synthesis as well as FA oxidation proteins, through down-regulation of the AMP-activated protein kinase/sirtuin 1 signaling pathway. In the CDAHFD-induced NASH mouse model, APE significantly enhanced liver histology and serum levels of liver damage. APE also significantly attenuated hepatic expression of mRNA and proteins related to FA synthesis, inflammation, and fibrosis. Furthermore, APE mitigated the expression levels of oxidative stress and endoplasmic reticulum stress. Overall, these discoveries indicate that Agrimonia pilosa has the potential to treat NASH by regulating hepatic lipid metabolism, alleviating inflammation, and mitigating oxidative stress.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

Kluyveromyces marxianus is an attractive thermotolerant yeast species for ethanol production because of its ability to utilize various carbon sources as a fermentation substrate. The use of thermotolerant microbes enables performance of high-temperature ethanol fermentation, which has several advantages including reduction of cooling costs and minimization of contamination risk. To improve K. marxianus for ethanol fermentation under stress conditions, two strains, DMKU 3-1042 and DMKU 3-118, were adapted for heat resistance and toxic substances in pulp wastewater from a paper mill, respectively, resulting in the generation of KMR1042 and KMR118, respectively. Both adapted mutants exhibited clumpy clusters of cells as pseudohyphae and altered colony morphology, and their sedimentation speeds were much faster than those of the corresponding parent strains. The two mutants showed stronger tolerance to various stresses and higher performance for ethanol production than those of the corresponding parent strains at high temperatures or in the presence of toxic substances. Genome sequencing analysis revealed that both mutants had disruption of the same gene, SWI5, despite adaptation under different stress conditions, suggesting that the formation of pseudohyphae is a common strategy of K. marxianus for coping with stresses.

When “hijacked” by compulsive behaviors that affect the reward and stress centers of the brain, functional changes in dopamine circuitry occur as the consequence of pathological brain adaptation. As a brain explanans for mental health, with a central functional role in behavioral regulation from healthy reward seeking to pathological adaptation to stress in response to adversity, we may use dopamine regulation in interaction with other brain mechanisms, as discussed herein, to gather a deeper insight into environmentally triggered mental health changes to understand, for example, specific behavioral changes observed during and after the COVID-19 pandemic. Pandemic-related adversities, the stresses they engendered, and the long lockdown periods where people had to rely on digital tools to get feed-back rewards via the internet can be seen as the major triggers of changes in motivation and reward seeking behavior worldwide. The pathological adaptation of dopamine-mediated reward circuitry in the brain offers a highly plausible explanation why, when pushed by fate and circumstance into a physiological brain state of anti-reward, human behavior and mental health changes almost inevitably depending on individual vulnerability to stress. A unified conceptual account that places dopamine function at the centre of the current global mental health context is proposed.

Oxidative stress (OS) is reported in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyzes the dismutation of superoxide anion with a protective role on endothelial cells. In chronic kidney diseases (CKD), OS and thyroid dysfunction (low T3 syndrome) are fre-quently present, but their relationship has not been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into: “acute hemodialytic pa-tients” (AH, 1-3 months of treatment) and “chronic hemodialytic patients” (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and the relation-ships with thyroid hormones. Two basal samples (“basal 1”, 3 days after the last dialysis and “basal 2”, 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs AH in all determinations. Moreover, they pre-sented lower TAC values. Dividing CH patients into two subgroups according to fT3 levels (nor-mal or low) we found significantly lower ec-SOD values in the group with low fT3 at basal, 5 and 10 min samples. Finally, a significant correlation was observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low T3 syndrome in CKD, suggest that low fT3 concentrations can influence ec-SOD activity and therefore contribute to possible endothelial oxi-dative damage in such a situation.

A rigid protruding surface, agitator and vortex generator often dissipate more energy than to produce a satisfied turbulence production. In contrast, a passively-oscillating flexible protruding surface has the ability in generating greater turbulence level. In the current study, a circular finite cylinder (cantilever) was used as the geometry of the rigid and protruding surface. They were varied through the aspect ratio (AR) and materials. Also, a local Reynolds number within the subcritical flow range (102<ReD<105) was considered. The results from the rigid protruding surface (finite cylinder) is served as a validation to the published results and benchmark to the improve-ment of the turbulence generated by the flexible protruding surface. It was mentioned in the pre-vious work that the increment of turbulence production by the flexible cylinder is speculated to be oscillation, this work investigates the validity of the speculation through manipulating the struc-tural stiffness of the flexible cylinder by employing different materials. The results have further demonstrated that the flexible cylinder is capable of generating a greater turbulence through the examination of turbulence intensity, turbulence production term and Reynolds stress. All the flex-ible cylinders that oscillate show increment in turbulence production but at a different percentage. The cylinders studied in this work ranged from the least structural stiffness (EVA), moderate (al-uminium) to the highest structural stiffness (carbon steel). Through studying the normalized am-plitude responses graph of the flexible cylinder, it is identified that the oscillating motion does in-deed contribute to increment. A further investigation into the results, it is found that the factor which governs the increment is the structural velocity instead of just oscillating motion alone.

The Coronavirus Disease 2019 (COVID-19) pandemic has had a major impact on the mental and physical health of hospitalized patients. In our study we focused on the onset of symptoms correlated with Post-traumatic stress disorder (PTSD), depression and physical disabilities in patients admitted to the Intensive Care Unit (ICU) because of a severe respiratory distress related to COVID-19 (COVID Group) compared with patients admitted to the same ICU for trauma and other medical conditions than COVID-19 (No-COVID Group). The physical symptoms and the level of disability were evaluated with the Glasgow Outcome Scale-Extended (GOS-E), the Quality of Life after Brain Injury (QOLIBRI) and the 3 levels version of EQ-5D (EQ-5D-3L) questionnaire; psychiatric symptoms were investigated using the Impact of Event Scale-Revised 22-item (IES-R), the Patient Health Questionnaire, 9-Item Version (PHQ-9) and the Generalized Anxiety Disorder Assessment, 7-items version (GAD-7). These questionnaires were administered 6 months after discharge. Patients in the No-COVID Group showed statistically significant more severe scores in all the physical assessments while similar relevant PTSD and depressive symptoms were reported in both groups. The results of the present study underline the psychopathological impact of being hospitalized in ICU because of COVID-19 even after 6 months from discharge ,suggesting the importance of assessing the psychiatric effects of COVID-19 in the long term in order to create supportive measures.

Background: According to metacognitive theory, Cognitive–Attentional Syndrome (CAS) is a transdiagnostic factor and main mechanism of psychopathology maintenance. The main goal of this study was to examine whether CAS predicted symptoms of stress and trauma-related symptomatology in the first months of the COVID-19 pandemic and three months later. Methods: Initially 1,792 participants were recruited online via social media; data was collected at two time points. Measures included the Cognitive–Attentional Syndrome Questionnaire, Adjustment Disorder – New Module 20, the International Trauma Questionnaire, and additional measures. Results: Structural equation modeling was conducted in order to determine relations between reported stressors, CAS, and symptomatology. At both time points, CAS was a significant mediator between stressors and symptoms of adjustment disorder. Despite the decrease in the intensity of adjustment disorder symptoms between waves, it was a significant predictor of other psychopathology at both time points, except for traumatic stress. Conclusions: The findings confirm the assumption that CAS is a transdiagnostic factor of psychopathology, and has a mediating role in the relationship between stressors and adjustment disorder and co-occurring symptomatology. The effect was particularly significant in the initial phase of the pandemic, which was highly stressful for many people.

Stress is one of the important factors affecting the growth and development of plants. In recent years, a large body of data on transcriptional changes in response to stress in plants has been obtained. Despite the fact that the important role of the regulation of translation in response to stress has been proven in plants, knowledge in this area remains extremely scarce. In this review, we focused on mRNA translation in the cytoplasm of higher plants. Most of the current research on the effects of translation has been done in yeast and mammalian systems. Translation factors and mechanisms are mostly conserved among eukaryotes; however, some differences are known to exist among plants. A comprehensive understanding of the complex apparatus of translation and its regulation in plants is required. In this work, we have tried to update modern ideas about the regulation of translation under conditions of abiotic stress.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

In this paper, based on the pseudo-totem pole (PTP) circuit, a family of five-level PTP dual boost converters (PDBC) is proposed. Dual boost converter has some unique advantages such as no bridge arm shoot-through risk and no switch body diode reverse recovery problem, so that it has a good application prospect. Compared with conventional three-level PTP converters, PDBCs has higher power density, higher efficiency, and low voltage and current stress. The topological derivation process, working principle, modulation and strategy of the topology are analyzed firstly. Further, the number of power devices, the switches voltage and current stress of the proposed topology is analyzed. Finally, a representative five-level PDBC experimental prototype is designed with AC input 220V/50Hz, DC output 400V/1kW, and peak efficiency of 98.27%. The experimental results show that the five-level PDBC proposed in this paper has higher efficiency and verify the correctness of the topology.

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

Environmental and occupational exposure to hexavalent chromium, Cr(VI), causes female reproductive failures and infertility. Cr(VI) is used in more than 50 industries and is a group-A carcinogen, mutagenic and teratogenic, and a male and female reproductive toxicant. Our previous findings indicate that Cr(VI) causes follicular atresia, trophoblast cell apoptosis, and mitochondrial dysfunction in metaphase II (MII) oocytes. However, the integrated molecular mechanism of Cr(VI)-induced oocyte defects are not understood. The current study investigates the mechanism of Cr(VI) in causing meiotic disruption of MII oocytes, leading to infertility in superovulated rats. Postnatal day (PND)-22 rats were treated with potassium dichromate (1 and 5 ppm) in drinking water from PND 22-29 and superovulated. MII oocytes were analyzed by immunofluorescence, and images were captured by confocal microscopy and quantified by Image Pro Plus software. Our data showed that Cr(VI) increased microtubule misalignment, missegregation of chromosomes, a bulged and folded actin cap, oxidative DNA and protein damage, increased DNA double-strand break, and DNA repair protein RAD51. Cr(VI) also induced incomplete cytokinesis and delayed polar body extrusion. Our study indicates that exposure to environmentally relevant doses of Cr(VI) caused severe DNA damage, distorted oocyte cytoskeletal proteins, and caused oxidative DNA and protein damage leading to infertility.

Silver in different forms is used for medical purposes from ancient times. It is not yet well known, which form of silver is more biocompatible and less toxic. Here we considered silver nanoparticles and silver citrate. Also, the relationships of neurotoxicity of silver compaunds with ageing factor is not yet described. To assess the role of nanoform in neurotoxicity of silver and role of ageing a long-term experiment was conducted. We had four control groups of intact mice and four experimental groups which were exposed to silver nanoparticles and silver citrate for two months. Four groups of mice were introduced into the experiment since the age of five months to assess ageing factors. It was shown that the nanoform does play a certain role in neurotoxicity of silver. Silver citrate seems to be a more preferable silver compound. Ageing can be regarded as a positive factor that neutralizes toxic action of silver compounds. It may be due to the development of physiological/cognitive functions with the age as well as adaptation to unnatural content in the individual cages that is definitely stressful for mice.

Polyhedral oligomeric silsesquioxane (POSS) is a suitable nanoscale reinforcement for thermosetting polymers, such as epoxy resin systems in order to modify its mechanical, thermal, and chemical properties. The inclusion of POSS in the epoxy resin at higher loading (greater than 1 wt.%), however, introduces the ductility during the fracture behavior of these nanocomposites. Consequently, the J-integral is used to quantify the fracture behavior of these materials and characterize the crack growth resistance curve against stable crack growth. A range of nanocomposites is prepared by adding 0.5, 1, 3, 5, and 8 wt.% of glycidyl POSS into DGEBF epoxy resin cured with an amine-based curing agent. From the fracture toughness experiment the load-displacement result confirms that when the POSS reinforcement is greater than 1 wt.%, the fracture behavior of the nanocomposite changes from brittle to ductile. For both brittle and ductile nanocomposites, the addition of POSS molecules improves the crack initiation toughness. The development of POSS–POSS compliant domains are reported previously, is attributed for this change in the failure behavior. The fractured images of POSS–epoxy nanocomposites, obtained using scanning electron microscopy, show that the increase in fracture resistance at higher values of POSS loading occurs due to the extensive shear yielding. Meanwhile, the increased fracture toughness at lower values of POSS loading occurs due to crack pinning and crack deflection.

Oxidative stress appears to be associated with more severe disease in WNV infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.

The endothelium plays a key role in blood vessel health. At the interface of the blood, it releases several mediators that regulate local processes and that protect against the development of cardiovascular disease. In this interplay, there is increasing evidence for a role of extracellular nucleotides and endothelial purinergic P2Y receptors (P2Y-R) in vascular protection. Recent advances have revealed that endothelial P2Y1-R and P2Y2-R mediate nitric oxide-dependent vasorelaxation as well as endothelial cell proliferation and migration, which are processes involved in the regeneration of damaged endothelium. However, endothelial P2Y2-R, and possibly P2Y1-R, have also been reported to promote vascular inflammation and atheroma development in mouse models, with endothelial P2Y2-R also being described as promoting vascular remodeling and neointimal hyperplasia. Interestingly, at the interface with lipid metabolism, P2Y12-R has been found to trigger HDL transcytosis through endothelial cells, a process known to be protective against lipid deposition in the vascular wall. Better characterization of the role of purinergic P2Y-R and downstream signaling pathways in determination of the endothelial cell phenotype in healthy and pathological environments has clinical potential for the prevention and treatment of cardiovascular diseases.

Background: COVID-19 has placed tremendous pressure on the global public health system and has changed daily life. Aim: To examine the relationships between the perceived threat, perceived stress, coping responses and infection control practices towards the COVID-19 pandemic among university students in China. Methods: Using a cross-sectional survey, 4,392 students were recruited from six universities in two regions of China. Methods: Data were collected via an online platform using self-reported questionnaires. Hierarchical multiple regression analyses were performed to predict the variables on COVID-19 infection control practices. Results: Pearson correlation coefficients showed a significant negative relationship between perceived stress and COVID-19 infection control practices. A significant positive relationship was observed between wishful thinking and empathetic responding, and infection control practices. Hierarchical multiple regression analyses revealed that gender, geographical location, perceived stress and emotion-focused and relationship-focused coping responses were predictors of COVID-19 infection control practices. Conclusions: The findings suggest that university students displayed moderate levels of stress, using wishful thinking and empathetic responses as coping strategies. Counselling services should therefore emphasise reassurance and empathy. Male university students tended to be less compliant with social distancing. Both counselling and public health measures should recognise the importance of gender differences. Nurses should integrate these findings into future health program planning and interventions.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells (i.e., adipocyte hypertrophy), low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orches-trated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new mature adipocytes appears the main instigator of the adi-pose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an al-tered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This novel paradigm (“expandability hypothesis”) challenges and extends previous “adipocentric view”, which implies a reduced plasticity of the adipose organ at the nexus between “unhealthy” fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation and cellular senescence. Finally, we discuss the sci-entific rationale for proposing adipose organ plasticity as a target to curb/prevent adi-posity-linked cardio-metabolic complications.

Maize (Zea mays subsp. mays) is the staple food crop in the world. In this study, multi-layer perceptron (MLP), support vector machine (SVM), genetic algorithm-based multi-layer perceptron (MLP-GA), and genetic algorithm-based support vector machine (SVM-GA) hybrid artificial intelligence algorithms were used for the prediction of drought tolerance and stress tolerance indices in teosinte maize lines. Correspondingly, the gamma test technique was applied to determine efficient input and output vectors. The potential of developed models was evaluated based on statistical indices and graphical representation. Results of gamma test based on the least value of gamma and standard error indices show that day of anthesis (DOA), day of silking (DOS), yield index (YI), and gross yield per plant (GYP) information vector arrangements were determined as efficient information vector combination for drought-tolerant index (DTI) as well as the stress-tolerant index (STI). The results of MLP, SVM, MLP-GA, and SVM-GA algorithms were compared based on statistical indices and visual interpretation that have satisfactory for prediction of the drought-tolerant index and stress-tolerant index in maize crop. It has also seemed that genetic algorithm-based hybrid models (MLP-GA and SVM-GA) were found a better prediction of the drought-tolerant index and stress-tolerant index in maize crop. Similarly, the SVM-GA model has the highest potential to forecast the DTI and STI in maize crops as compared to MLP, SVM, MLP-GA models.

The cyclic load applied to civil and mining structures can lead to a reduction of the materials’ strength, different from that which would occur with a monotonous load. Numerous cases can be found where the decay of the rock parameters subjected to this type of stress leads to progressive or sudden collapse: among them, tunnel walls, pillars and slabs in mining operations, roads with a heavy vehicle transit, abutments of bridges and dams can be quoted. The topic can therefore be fundamental for a correct structural design, to avoid problems during the life of the structure. However, given the heterogeneity of the rock materials and the difficulty of their characterization under this aspect, an unequivocal analysis is hardly achievable. Then, the discussion initially develops through a general historical review of the concept of fatigue, with a synthetic collection of case histories. The laboratory tests on rock samples are then examined and the most important results obtained are discussed. Finally, a comparison between different types of tests is proposed. The experimental data are expressed through the Wӧhler diagram. The goal is to fill the lack of design codes or standards in the field of cyclic stresses applied to rock materials, the understanding of its effect being of great interest in order to apply suitable parameters in the design phase.

Introduction: Heat is a kinetic process whereby energy flows from between two systems; hot-to-cold objects. In oro-dental implantology, conductive heat transfer/(or thermal stress) is a complex physical phenomenon to analyze and consider in treatment planning. Hence, ample research has attempted to measure heat-production to avoid over-heating during bone-cutting and -drilling for titanium (Ti) implant-site preparation and insertion, thereby preventing/minimizing early (as well as delayed) implant-related complications and failure. Objective: Given the low bone-thermal conductivity whereby heat generated by osteotomies is not effectively dissipated and tends to remain within the surrounding tissue (peri-implant), increasing the possibility of thermal-injury; this work attempts to obtain an exact analytical solution of the heat equation under exponential thermal-stress, modeling transient heat transfer and temperature changes in Ti implants upon hot-liquid intake. Materials and Methods: We investigate the impact of the material, the location point along implant length, and the exposure time of the thermal load on temperature changes. Results: Despite its simplicity, the presented solution contains all the physics and reproduces the key features obtained in previous numerical analyses studies. To the best of knowledge, this is the first introduction of the intrinsic time, a “proper” time that characterizes the geometry of the dental implant, where we show, mathematically and graphically, how the interplay between “proper” time and exposure time influences temperature changes in Ti implants, under the suitable initial and boundary conditions. Conclusions: This work aspires to accurately complement the overall clinical diagnostic and treatment plan for enhanced bone-implant interface, implant stability and success rates, whether for immediate or delayed loading strategies.

The paper describes the Field Boundary Element Method applied to the fracture analysis of a 2D rectangular plate made of Functionally Graded Material to calculate Mode I Stress Intensity Factor. The object of the Field Boundary Element Method is the transversely isotropic plane plate. Its material presents an exponential variation of the elasticity tensor depending on a scalar function of position, i.e., the elastic tensor results from multiplying a scalar function by a constant taken as a reference. Several examples using a parametric representation of the structural response show the suitability of the method that constitutes a sight of Stress Intensity Factor evaluation of Functionally Graded Materials plane plates even in the case of more complex geometries.

During type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to the unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid the loss of beta-cells that will jeopardize the transplant´s outcome, several strategies are being studied. We have previously shown that prolactin induces protection against pro-inflammatory cytokines and redox imbalance-induced beta-cell death by increasing heat shock protein B1 (HSPB1) levels. Since the role of HSPB1 in beta cells has not been deeply studied, we investigated the mechanisms involved in unbalanced protein homeostasis caused by intense ER stress and overload of the proteasomal protein degradation pathway. We tested whether HSPB1-mediated cytoprotective effects involved UPR modulation and improvement of protein degradation via the ubiquitin-proteasome system. We demonstrated that increased levels of HSPB1: attenuated levels of pro-apoptotic proteins like CHOP and BIM, increased protein ubiquitination and the speed of proteasomal protein degradation. Our data showed that HSPB1 induced resistance to proteotoxic stress and thus enhanced cell survival via an increase in beta-cell proteolytic capacity. These results could contribute to generate strategies aiming at optimization of beta-cell replacement therapies.

Objective: The aim of the study was to evaluate the influence of a suburethral sling implantation on the urge symptoms in patients suffering mixed urinary incontinence (MUI) with predominant stress component in case of. Material and methods: The study group was 220 woman with stress urinary incontinence (SUI), among them 35 women with stress-predominant MUI, treated primary with suburethral sling implantation. In 85.7% (N=30) TOT and in 14.3% (N=5) TVT was performed. The clinical symptoms and QOL were assesed before and after treatment using bladder diary and QOL questionnaire. Other additional treatment was also evaluated.Results: Subjective improvement of urge symptoms was observed in 97.1% of woman in the study group. ‘Wet OAB’ symptoms were reduced from 68.6% to 28.6% after sling procedure. Nocturia and pollakiuria were reduced from 45.7% to 11.4% and 8.6% respectively. Nocturia and pollakiuria de novo were observed in 2 (5.4%) and 1 (2.7%) patients respectively. After the sling procedure in 28.6 % (N=10) pharmacotherapy with solifenacin was administered for 2-4 months, in 8.6% (N=3) intravesical injection of botulinum toxin was performed due to persisting OAB symptoms.Conclusion: suburethral sling implantation in woman with stress- predominant MUI, although dedicated to treat SUI symptoms, seems to improve also the urge component of MUI.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

The potential of the Additive Manufacturing technologies is impeded by the surface finish obtained on the as-manufactured material. Therefore, the influence of various surface treatments, commonly applied to space hardware, on the mechanical properties of three selected metallic alloys (SS316L, AlSi10Mg, Ti6Al4V) prepared by using Selective Laser Melting (SLM) and Electron Beam Melting (EBM) additive manufacturing processes have been investigated. Within this study, SLM using EOS M400 and EOS M280 equipment and in addition EBM using an ARCAM Q20 machine have been applied for sample manufacturing. A half-automated shot-peening process followed by a chemical and/or electrochemical polishing or Hirtisation® process has been applied in order to obtain lower surface roughness compared to their as-received states. Special emphasize has been taken on their tensile, fatigue, and fracture toughness properties. In addition, their stress corrosion cracking (SCC) behaviour including microstructural analysis using HR-SEM have been investigated.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and 3 (PON1 and PON3) protein expression have been described in tissues with no PON1 and PON3 gene expression. In the present study, we aimed to examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: We used peroxidase-based and fluorescence-based immunohistochemistry in 5 brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3 positive staining in star-shaped cells surrounding Aβ plaques in all Tg2576 mouse brain regions studied. Although we could not co-localize PON1 and PON3 with astrocytes, brain star-shaped cells, we found some co-localization of PON3 with microglia. Conclusions: These results suggest that 1) PON1 and PON3 cross the blood-brain barrier in discoidal HDLs and are transferred to specific brain cell types, and 2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular cell types, likely astrocytes and microglia, in AD pathology, and potentially in other neurodegenerative diseases

In the last decades farm animals kept in confined and mechanically ventilated livestock buildings are increasingly confronted with heat stress (HS) due to global warming. These adverse conditions cause a depression of animal health and welfare and a reduction of the performance up to an increase of the mortality. To facilitate sound management decisions, livestock farmers need relevant arguments, which quantify the expected economic risk and the corresponding uncertainty. The economic risk was determined for the pig fattening sector based on the probability of HS and the calculated decrease in the gross margin. The model calculation for confined livestock buildings showed, that HS indices calculated by easily available meteorological parameters can be used for assessment quantification of indoor HS, which is so far difficult to determine. These weather-related HS indices can be applied not only for an economic risk assessment but also for a weather-index based insurance for livestock farms. Based on the temporal trend between 1981 and 2017, a simple model was derived to assess the likelihood of HS for 2020 and 2030. Due to global warming, the return period for a 90-percentile HS index is reduced from 10 years in 2020 to 3-4 years in 2030. The economic impact of HS on livestock farms was calculated by the relationship between an HS index based on the temperature-humidity index (THI) and the reduction of the gross margin. From the likelihood of the HS and this economic impact function, the probability of the economic risk could be determined. The reduction of the gross margin for a 10 year return period was determined for 1980 with 0.27 € per year and animal place and increased by the 20-fold to 5.13 € per year and animal place in 2030.

Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far being focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H2O2 levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12 and 24h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. DCF-DA staining was performed for H2O2 imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC-) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton.

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.

Specific aquaporins (AQP), called peroxyporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasting during oxidative stress. Another target involved in oxidative stress is the Sigma1 Receptor (S1R), since its activation is triggered by oxidative or endoplasmic reticulum stress. Herein we evaluated the effect of S1R modulators on AQP-dependent water permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in Hela cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. All compounds except one were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together, our results support the hypothesis that the investigated compounds act as dual aquaporin and Sigma1 receptor (DAS) modulators. The finding that small molecules can modulate both AQP and S1R opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, like cancer and degenerative diseases.

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

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 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 &amp; 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.