Chloroplasts are ancient organelles responsible for photosynthesis and various biosynthetic functions essential to most life on Earth. Many of these functions require tightly controlled regulatory processes to maintain homeostasis at the protein level. One such regulatory mechanism is the ubiquitin-proteasome system whose fundamental role is increasingly emerging in chloroplasts. In particular, the role of E3 ubiquitin ligases as determinants in the ubiquitination and degradation of specific intra-chloroplast proteins. Here, we highlight recent advances in understanding the roles of plant E3 ubiquitin ligases in chloroplast function.

A 9.4 T/400 MHz superconducting magnet with a warm bore of 60 mm is being designed. The 400 MHz NMR magnet is composed of 9 coaxial coils to generate a central field of 9.4 T. The magnetic field homogeneity is better than 4 ppm for 50 mm diameter spherical volume (DSV) and better than 1 ppb for 5 mm DSV. Three types of NbTi strands were used to reduce the cost of the superconducting materials. A preload with 80 MPa was exerted on the superconducting coils and over-banding with stainless steel was adopted to release the stress from the electromagnetic forces. The magnet will be operated in persistent mode with superconducting joints to reduce the field decay. The pulse tube cryocooler with a cooling capacity of 1 W at 4.2 K can be used to reduce the liquid helium evaporation and vibration during operation. The magnet will be equipped with Bi2223/AgAu HTS current leads to reduce the heat losses. In this paper, the design of the 9.4 T NMR superconducting coils, electromagnetic field calculations, and stress analysis of the superconducting coils were presented.

Heart failure (HF) has become a public health problem, but exact pathophysiology is still unknown. Western diet characterised with high sugar, high fat, red meat and processed meat, eggs, fried foods and sweetened beverages, may cause oxidative stress and inflammation, leading to oxidative dysfunction and adverse effects on cardiac-ultra-structure. However, only little is known about oxidative function of the of the myocardium and how oxidative dysfunction predispose Ca-overloading resulting in to physio-pathological remodelling leading to HF. Antioxidants such as flavonoids and polyphenolics, omega-3 fatty acids, vitamins, minerals as well as essential and nonessential amino acids that are rich in Indo-Mediterranean type of diets, may have protective roles in maintaining oxidative functions of the heart. The cardiac cells use fatty acids and glucose for the metabolic functions depending upon physiological and metabolic requirements. Apart from glucotoxicity, lipotoxicity is also damaging to cardiac cells which worsen in presence of deficiency of endogenous antioxidants and lower exogenous antioxidants in the diet. There is increased production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) due to high sugar and high fat diets, leading to oxidative dysfunction and Ca-overloading. The biological changes may begin with physiological remodelling to pathological remodelling due to oxidative damages. High fat diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve ejection fraction in a mouse model of HF. It is possible that increased supplementation of High Exogenous Antioxidant Restorative Treatment (HEART) diet; polyphenolics and flavonoids, vitamins, minerals, arginine, with omega-3 fatty acids, and cessation of red meat and egg may further improve the oxidative function of cardiac cells, resulting in the prevention and improvement in the earliest of the Six Stages of HF. Cohort studies and randomised, controlled trials would be necessary for demonstration of the role of HEART diet in the management of HF.

Based on the textured controllable interface effect, the dynamic performances of the textured and ordinary pilot valve are analyzed experimentally, and the influence of the textured controllable interface on the response of pilot valve is studied. Results show that when Pin is small, the textured surface shortens the reciprocating time of valve core, increasing the flow rate, and speeds up the piston stroke of oil cylinder. The valve core actions much more stable and sensitivity. Meanwhile, combined with the theoretical calculation, the operation mechanism of texturing the pilot valve is analyzed. It is concluded that the stress of textured valve core sealing surface is greater than that of ordinary one, and the pressure difference gradually decreases with the increase of Pin, and the flow difference is basically the same as the force on the sealing surface. This indicates that the textured surface improves lubrication characteristics, reduces the friction between components. The textured valve makes the velocity changes gently, and enhances the responsiveness and stability of the valve. Those related results provide a new idea for enhancing the response design of the pilot valve.

Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.

In response to the COVID-19 pandemic, social distancing measures were put into place to flatten the pandemic curve. It was projected older adults were at increased risk for poor psychological and health outcomes resulting from increased social isolation and loneliness. However, little re-search has supported this projection among community-dwelling older adults. While growing body of research has examined the impact of the COVID-19 pandemic on older adults, there is a paucity of qualitative research that captures the lived experience of community-dwelling older adults. The current study aimed to better understand the lived experience of community-dwelling older adults during the first six months of the pandemic. Semi-structured one on one interviews were conducting with independent living older adults aged 65 years and older. After achieving saturation, 22 interview were analyzed using inductive thematic analysis. Following a recursive process, two overarching themes emerged from the data: perceived threat and challenges of the pandemic and coping with the pandemic. Specifically, participants reflected on the threat of contracting the virus and challenges associated with living arrangement, social isolation, and financial insecurity. Participants shared their coping strategies to maintain health and wellbeing, including behavioral strategies, emotion-focused strategies, and social support. Overall, this re-search highlights resilience among older adults during the first six months of the pandemic.

Objectives To delineate the features of ischemic stroke patients and their caregivers that may predict distress, depression, and anxiety symptoms in the caregivers. Methods The Hospital Anxiety and Depression Score (HADS), Zarit Burden Interview (22 item-ZBI), and Perceived Stress Scale (PSS-10) were used to assess caregivers' burden, stress, depressive, and anxiety symptoms. We performed partial least square-structural equation modeling (PLS-SEM) in order to delineate a multi-step mediation model.Results In this study, 97 stroke patients and their caregivers were included. Multiple regression analysis revealed that ZBI-personal strain and stroke of other determined etiology explained 15.0 percent of the variance in the HADS depression score (p=0.001). We discovered that the caregiver's underlying disease and the National Institute Stroke Score (NIHSS) of the patients explained 13.6 percent of the variance in the total ZBI score of the caregivers (p=0.001). The total ZBI score, the presence of lacunar circulation infarction in the patients, and the caregiver's underlying disease explained 40.9 percent of the variance in the total PSS score of the caregivers (p <0.001). Moreover, PLS analysis showed that the NIHSS and the caregiver's underlying disease had significant indirect effects on the HADS score which were mediated by the ZBI score. Conclusions A large part of the variance in stress and depressive scores in caregivers of ischemic stroke patients is determined by the patient's disability, dependency, cognition, and stroke phenotypes, as well as the caregiver's health status and burden. Screening for the aforementioned factors in ischemic stroke caregivers is critical.

Koala (Phascolarctos cinereus) is an iconic folivorous marsupial native to the sclerophyll forests and woodlands of Australia. Due to the ever-changing habitat, this species is highly vulnerable to anthropogenic factors such as habitat loss and fragmentation, and this is reflected in the increasing number of injured and/or diseased koalas over the years. The majority of adult koalas admitted at wildlife hospitals are deceased, either due to natural causes, or have to be euthanized. Thus, orphaned koala joeys constitute a substantial number of wildlife rescues, and mortality is also prevalent in koala joeys being hand-reared/rehabilitated, with little knowledge about the causes of such high rates of mortality. Wildlife hospitals/rehabilitation centres are inherently stressful, and although the hypothalamic–pituitary–adrenal (HPA) axis plays a vital role in mediating the stress endocrine function (by producing glucocorticoids such as cortisol), there are no studies quantifying glucocorticoids in koala joeys. To contribute to this dearth of research, we sampled a total of seven individuals residing at Port Macquarie Koala Hospital and noted their clinical information. Faecal samples were collected from all seven koala joeys during routine cage cleaning. In total, 123 faecal samples were collected, processed and analysed for cortisol using enzyme-immunoassay (EIA). We used the iterative baseline approach to determine baseline and peak concentrations of FCM in koala joeys. Baseline concentrations ranged between 14.11 ng/g – 51.10 ng/g (healthy – sick), whereas, peak FCM concentrations ranged between 25.65 ng/g – 56.58 ng/g (healthy – sick). There was a significant difference (p &lt; 0.05) between FCM concentrations of healthy and impaired individuals. Healthy individuals displayed relatively consistent FCM concentrations, whereas, diseased individuals displayed a significant increase in FCM concentrations over time. Our study provides the first record of baseline and peak FCM concentrations in rescued koala joeys with their associated clinical condition. Future studies can use the iterative baseline approach to determine FCM concentration in wild koala joeys that can serve as a baseline to compare glucocorticoid levels of rescued joeys.

We compared two approaches to non-invasive proximal sensing of the early changes in fresh-cut lettuce leaf quality: hyperspectral imaging and imaging PAM-fluorometry of chlorophyll contained in the leaves. The assessments made by the imaging techniques were confronted with the quality assessments made by traditional biochemical assays: relative water content and foliar pigment (chlorophyll and carotenoid) composition. The hyperspectral imaging-based approach provided the highest sensitivity to the decline of fresh-cut lettuce leaf quality taking place within 24 h from cutting. Using of the imaging PAM was complicated by (i) weak correlation of the spatial distribution pattern of the Qy parameter with the actual physiological condition of the plant object and (ii) its high degree of heterogeneity. Accordingly, the imaging PAM-based approach was sensitive only to the manifestations of leaf quality degradation only at advanced stages of the process. Sealing the leaves in the polyethylene bags slowed down the leaf quality degradation at the initial stages (&lt; 3 days) but promoted its rate at more advanced stages, likely due to build-up of ethylene in the bags. An approach was developed to the processing of hyperspectral data for non-invasive monitoring of the lettuce leaves with a potential for implementation in greenhouses and packinghouses.

Tinnitus is a phantom sound perception in the ears or head and can arise from many different medical disorders. Currently, there is no standard treatment for tinnitus that reliably reduces tinnitus. Individual patients reported that acupressure at various points around the ear can help to reduce tinnitus, which was investigated here. With this longitudinal observational study, we report a systematic evaluation of auricular acupressure on 39 tinnitus sufferers, combined with a self-help smartphone app. The participants were asked to report about tinnitus, stress, mood, neck and jaw muscle tensions twice a day using an ecological momentary assessment study design for six weeks. On average, 123.6 questionnaires per person were provided and used for statistical analysis. The treatment responses of the participants were heterogeneous. On average, we ob-served significant negative trends for tinnitus loudness (Cohen’s d effect size: -.861), tinnitus dis-tress (d = -.478), stress (d = -.675), and tensions in the neck muscles (d = -.356). Comparison with a matched control group revealed significant improvements for tinnitus loudness (p = .027) and self-reported stress level (p = .003). The positive results of the observational study motivate fur-ther research including a randomized clinical trial and long-term assessment of the clinical im-provement.

We aimed to evaluate the protective effects of acetyl-xylogalactan on the activity of RAW264.7 macrophages against heat stress. To this end, we assessed cell survival, phagocytic activity, in-tracellular Ca2+ level, mitochondria potential exchange, apoptotic assay findings, galactosidase activity and the RNA-seq by NGS and real-time polymerase chain reaction (PCR) expression. In our evaluation of macrophage morphology at 37°C and 41°C, the macrophages showed an oval shape at 41°C , unlike the spindle shape at 37°C. Therefore, 41°C was chosen as the heat stress condition. Subsequently, we designed an experiment to evaluate changes in the RAW264.7 macrophages after acetyl-xylogalactan treatment under heat stress. The survival of RAW264.7 macrophages treated with acetyl-xylogalactan was higher than that of controls that were not treated with acetyl-xylogalactan. Moreover, on the basis of the results of the annexin-V detection assay, the apoptotic activity of macrophages appeared to have reduced after treatment with ac-etyl-xylogalactan. Moreover, treatment with acetyl-xylogalactan resulted in a stronger recovery trend in the intracellular Ca2+ and mitochondrial membrane potential after heat stress. RNA sequencing and real-time polymerase chain reaction (PCR) illustrated that Sarcodia suieae acetyl-xylogalactan could upregulate the expression of the anti-apoptosis Cflar gene and down-regulate the expression of the apoptosis factors Ddit3, and Hyou1 to protect macrophages under heat stress.

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). And Arabidopsis Long Hy-pocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in plant stress response signal network remains unknown. Here, we described the func-tion of the HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2 which positively mediated the expression of downstream stress-related genes of RD29A, RD29B and DREB2A. Further quantitative proteomics showed the patterns of 7,391 proteins under salt stress. HY2 was then found to specifically regulate 215 differentially regulated proteins (DRPs) which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic & metabolic, hormone response (SA, JA, ABA, ethylene), reactive oxygen spe-cies (ROS) metabolic, photosynthesis and detoxification pathway to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifi-cally-regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to re-sist salt stress.

Mulberry is an economically significant crop for the sericulture industry worldwide. Stresses such as drought exposure have a significant influence on plant survival. Metabolome directly reflects plant physiological status; thus, a way to assess this impact is to perform a global metabolomic analysis. This study investigated the effect of drought stress on mulberry Yu-711 metabolic balance using a liquid chromatography-mass spectrometry (LC-MS) based on an untargeted metabolomic approach. For this objective, Yu-711 leaves were subjected to two weeks of drought stress treatment and control without drought stress. Multivariate and univariate statistical analyses highlighted numerous differentially-accumulated metabolic elements as a function of time and treatment. Drought stress led to a more differentiated metabolites response than the control. We found that the levels of total lipids and galactolipids, and phospholipids (PC, PA, PE) were significantly altered, producing 48% of the total differentially expressed metabolites. Fatty acyls were the most abundant lipids expressed and decreased considerably by 73.6%. Prenol lipids class of lipids increased in drought leaves. Other classes of metabolites, including polyphenols( flavonoids and cinnamic acid), organic acid (amino acids), carbohydrates, benzenoids, and organoheterocyclic, all had a dynamic trend in response to the drought stress. However, their levels under drought stress generally decreased significantly compared to the control. These results provide an overview of the metabolic profile of the mulberry plant through differentially-accumulated compounds and provide a better understanding of global plant metabolic changes in defense mechanisms.

Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.Conclusions: Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

There are experimental evidences that chronic social defeat stress is accompanied by development of anxiety- and depression-like state as well as downregulation of serotonergic genes in the midbrain raphe nuclei of male mice. The study was aimed at investigating the effect of chronic lithium chloride (LiCl) administrations on anxiety behavior and the expression of serotonergic genes in the midbrain raphe nuclei of affected mice. The pronounced anxiety in male mice was caused by chronic social defeat stress in daily agonistic interactions. After 6 days of social stress, defeated mice were treated with saline or LiCl (100 mg/kg, i.p. two weeks) against the background of continuing agonistic interactions. The level of anxiety was assessed using behavioral tests. The effect of chronic treatment with LiCl on the expression of serotonergic genes in the midbrain rapher nuclei was also studied. Mild anxiolytic effects of LiCl were found on communication in the partition test. Anxiogenic-like effects assessed using the elevated plus-maze and social interaction tests were found. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei. The effects of chronic LiCl treatment depends on the method of treatment, psychoemotional state, and experimental context (tests).

Cacao is an understory plant cultivated under full-sun monocultures to multi-strata agroforestry systems, where cocoa trees are planted together with fruit, timber, firewood, and leguminous trees, or grown within thinned native forests. Under agroforestry systems of cultivation, cacao is subjected to excess shade due to high density of shade trees, and overgrown or unmanaged pruning of shade trees. Cacao is tolerant to shade, and the maximum photosynthetic rate occurs around irradiance of 400 μmol m⁻² s⁻¹ but excess shade reduces the irradiance further which is detrimental to photosynthesis and growth functions. Intra-specific variation is known to exist in cacao for the required saturation irradiance. A greenhouse study was implemented with 58 cacao genotypes selected from four geographically diverse groups: (i) wild cacao from river basins of the Peruvian Amazon, (PWC), (ii) Peruvian farmers’ collection (PFC), (iii) Brazilian cacao collection (BCC) and (iv) national and international cacao collections (NIC). All the cacao genotypes were subjected to 50% and 80% shade where photosynthetic photon flux density (PPFD) was 1000 and 400 μmol m^-2 ּs^-1 respectively. Intra-specific variations were observed for growth, physiological and nutritional traits, and tolerance to shade. Cacao genotypes tolerant to shade were: UNG-77 and UGU-130 from PWC; ICT-2173, ICT-2142, ICT-2172, ICT-1506, ICT-1087, and ICT-2171 from the PFC; PH-21, CA-14, PH-990 and PH-144 from BCC; and ICS-1, ICS-39, UF-613 and POUND-12 from NIC. Genotypes that tolerate excess shade might be useful plant types to maintain productivity and sustainability in agroforestry systems of cacao management.

The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

This paper aims to contribute to the advancement of scientific knowledge about the impact of the COVID-19 pandemic on social workers and the social work profession in Romania. Research has shown that social work is a profession at high risk for developing the burnout syndrome, which has many detrimental effects on both social workers and the clients that they serve. Two conceptual models are used to frame the discussion: the theoretical framework of VUCA (volatility, uncer-tainty, complexity, and ambiguity) to discuss the challenges of the unprecedented context the COVID-19 pandemic has created for social workers; stress and burnout to explain the negative impact of this period of time. Based on convergent mixt methods, the study sample consisted of 83 social workers employed in statutory and private social services in Romania, from different fields of intervention. Results show that 25,3% of respondents suffer from a high level of burnout and 44.6% scored in a range that indicate a medium level of burnout. A group of 31.1% have managed to handle stress factors in a healthy manner. Main stressors found are especially personal (fear of contamination, personal and family) and work-related factors (workload, new legislative rules and decisions, inconsistency, instability, ambiguity of managerial decisions, or even their absence or non-assumption, lack of clarity of working procedures, limited managerial and supervisory support, limited financial resources), less than client related factors (lack of direct contact, risk of contami-nation in two ways, managing beneficiaries fears, difficulties related to technology and digital skills). Study results point to the importance of organizational support and developing a self-care plan that help protect against occupational stress and burnout. Recommendations are made putting forward the voice of fieldworkers and managers fostering initiatives and applications of sustainability-based measures and activities designed to deal with the challenges of the VUCA environment.

Calcineurin B-like proteins (CBL)-interacting protein kinases (CIPKs) by interacting with CBLs regulate developmental processes, hormone signalling transduction and mediate stress responses in plants. Although the genome of chickpea is available, information of CIPK gene family has been missing in chickpea. Here, a total of 22 CIPK encoding genes were identified in chickpea and characterized by in silico methods. We found a high structural conservation in chickpea CIPK family. Our analysis showed that chickpea CIPKs have evolved with dicots from common ancestors, and extensive gene duplication events have played an important role in evolution and expansion of CIPK family in chickpea. Most chickpea CIPK proteins localize in cytoplasm and nucleus. Promoter analysis revealed various cis-regulatory elements related to plant development, hormone signaling and abiotic stresses. Expression analysis indicated that CIPKs are significantly expressed in a spectrum of developmental stages, tissue/organs that hinted their important role in plant development. Several CIPK genes had specific and overlapping expressions in different abiotic stresses and seed development stages, suggesting the important role of CIPK family in abiotic stress signaling, and seed development in chickpea. Thus, this study provides the avenue for detailed functional characterization of CIPK family in chickpea and other legume crops.

This study aims to develop a clinical trial to test the efficacy of a Mindfulness Based Stress Re-duction (MBSR) and Self Compassion (SC) Program on self-reported values of anxiety, depres-sion, and stress in parents of children with Autism Spectrum Disorder (ASD) in primary school, in order to assess their integration into the framework of community intervention programs in Spain. Methods: A brief 8-week training program using Mindfulness based intervention (MBSR) and self-compassion (SC) has been applied to ten parents from the Valencian ASD parents’. Partici-pants were assigned to two groups, both groups received the same treatment but at two different measurement moments. Depression, Anxiety, Stress, Satisfaction with Life and Mindful Atten-tion Awareness measurements were assessed, in all participants, in three testing moments. Results: Analysis of Variance results suggested that MBSR and SC training reduces stress and anxiety and increases Mindful Attention Awareness. No significant changes were found in Life Satisfaction measurements. Conclusions: The small number of participants prevents us from generalising the results found. More MBSR and SC clinical trials are needed in parents of ASD with results on anxiety, depression and stress in order to demonstrate the relevance of the inclusion of these programmes in community-based early intervention services.

This review presents a comprehensive and systematic study of the field of bacterial plant biostimulants and considers the fundamental and innovative principles underlying this technology. Plant biostimulants are an important tool for modern agriculture as part of an integrated crop management (ICM) system; helping make agriculture more sustainable and resilient. Plant biostimulants contain substance(s) and/or microorganisms whose function when applied to plants or the rhizosphere, is to stimulate natural processes to enhance plant nutrient uptake, nutrient use efficiency, tolerance to abiotic stress, biocontrol, and crop quality. The use of plant biostimulants has gained substantial and significant heed worldwide as an environment-friendly alternative for sustainable agricultural production. Presently, there is an increasing curiosity of industry and researchers in microbial biostimulants especially, bacterial plant biostimulants (BPBs) to improve crop growth and productivity. The BPBs that are based on PGPR (plant growth-promoting rhizobacteria) play plausible roles to promote/stimulate the crop plant growth through several mechanisms that include, i) nutrient acquisition by nitrogen (N₂) fixation and solubilization of insoluble minerals (P, K, Zn), organic acids and siderophores, ii) antimicrobial metabolites and various lytic enzymes, iii) action of growth regulators and stress-responsive/induced phytohormones, iv) ameliorating abiotic stress like drought, high soil salinity, extreme temperatures, oxidative stress, and heavy metals by using different modes of action, and v) plant defense induction modes. Presenting here is a brief review emphasizing the applicability of BPBs as an innovative exertion to fulfill the current food crisis.

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist while pathophysiological overlap, including microbiota changes, may play a role. The aim of the study is to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammation and oxidative stress markers, and faecal microbiota in adult patients with depressive disorders depending on the co-occurance of MetS. The trial will be a four-arm, parallel group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks. The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, HDL cholesterol, triglicerides, fasting glucose, faecal microbiota composition and the level of some faecal microbiota metabolites, as well as inflammation markers and oxidative stress parameters in serum. The trial may establish a safe and easy-to-use treatment option as an adjunct in a subpopulation of depressive patients only partially responsive to pharmacologic treatment. (ClinicalTrials.gov identifier: ).

Polyphenols represent a group of secondary metabolites of plants which have been analyzed as potent regulators of multiple biological processes, including cell proliferation, apoptosis and autophagy, among others. These natural compounds exhibit beneficial effects and protection against inflammation, oxidative stress and related injuries including metabolic diseases, such as cardiovascular damage, obesity and diabetes and neurodegeneration. In the present review, we report the main biological effects in relationship to autophagy regulation in response to different dietary polyphenols and its impact on metabolic and neurodegenerative diseases

Early detection of stress can prevent us from suffering from a long-term illness such as depression and anxiety. This article presents a scoping review of stress detection based on electrodermal activity (EDA) and machine learning (ML). From an initial set of 395 articles searched in six scientific databases, 58 were finally selected according to various criteria established. The scoping review has made it possible to analyse all the steps to which the EDA signals are subjected: acquisition, preprocessing, processing and feature extraction. Finally, all the ML techniques applied to the features of this signal have been studied for stress detection. It has been found that support vector machines and artificial neural networks stand out within the supervised learning methods given their high performance values. On the contrary, it has been evidenced that unsupervised learning is not very common in the detection of stress through EDA. This scoping review concludes that the use of EDA for the detection of arousal variation (and stress detection) is widely spread, with very good results in its prediction with the ML methods found during this review.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

The objective of this study was to evaluate biomarkers of heat stress (HS) from automatic milking system (AMS), the relationships between measurements of temperature-humidity index (THI) and reticulorumen ph and temperature and some automatic milking systems parameters in dairy cows (rumination time (RT), milk traits, body weight (BW) and consumption of concentrate (CC)) during summer period. The experiment was carried out on a dairy farm at 54.9587408, 23.784146. Lithuanian Black and White dairy cows (n=365) were selected. The cows were milked with Lely Astronaut® A3 milking robots with free traffic. The rations were calculated to meet physiological requirements of the animals. Daily milk yield, rumination time, body weight, milk fat and protein ratio were collected from the Lely T4C management program for analysis. The pH and temperature of the contents of cow reticulorumen were measured using specific smaX-tec boluses manufactured for animal care. The daily humidity and air temperature in the farm zone were obtained from the adjacent weather station (2 km away). According this study during HS, the higher THI had positive correlation with ML, which show tendencies to increase risk of mastitis, and decrease CC, RT, BW, MY, reticulorumen ph and F/P. Some biomarkers of HS can be milk yield, milk lactose, somatic cell count, concentrate conception, rumination time, body weight, reticulorumen ph and milk fat – protein ratio. We can recommend to monitoring these parameters in the herd management program to identify possibility of heat stress.

Alzheimer’s disease is a prominent neurological disorder, which leads to progressive dementia. The microtubule-associated protein Tau is been considered as one of the major causes of Alzheimer’s disease. Physiologically Tau assists in the stabilization of microtubules, contrary to this the pathological state of Tau results in the formation of neurotoxic tangles of Tau. The posttranslational modifications, such as GSK-3β-mediated Tau phosphorylation results in the generation of Tau pathology. Neuroinflammation generated in Alzheimer’s disease, contributes to elevated body temperature. The aim of present work is to study the effect of high temperature on Tau phosphorylation. The neuroblastoma cells were exposed to heat stress for 40 minutes. The immunofluorescence and western blot studies suggested that high temperature increases the levels of GSK-3β in cells. Heat stressed cells was also observed to have elevated levels of phosphorylated Tau. Additionally, heat stressed cells found to have modulated nuclear transport as the level of Ran was reduced. The results of present work suggested that increased temperature could be considered as a risk factor in Alzheimer’s disease as it elevated the GSK-3β levels in cells thus, resulting in increased Tau phosphorylation.

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. Aim of the study. To study the associations between low α-klotho status and calcium metabolism in relation to iron status in children with TDT. Methods. α-klotho, calcium, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children. Results. A meaningful part of TDT patients showed lowered α-klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload biomarkers and the number of blood transfusions (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions. Conclusion. In TDT, iron overload and its consequences may induce lowered levels of α-klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

Background: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. Methods: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58). Results: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). Conclusion: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

We aimed to test the hypothesis that serum 25-hydroxyvitamin D3 [25(OH)D] concentration is associated with mental health and life stress measures in young adults, and investigate sex and racial disparities in these associations. This study comprised 327 black and white participants. Depression, trait anxiety, perceived stress, and hostility were measured by validated instruments: Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Cook-Medley Hostility Scale (CMHS). Linear regression was used to estimate correlations between serum 25(OH)D concentration and mental health measurements in total population and in subgroups stratified by sex and race. In this sample (28.2 ± 3.1 years, 48% male, 53% black), serum 25(OH)D concentration was negatively related to BDI, STAI, PSS, total CMHS score and the majority of CMHS subscale scores (p-values < 0.05). Stratified by sex, most of these associations remained significant only in women (p-values < 0.05). Stratified by race, higher 25(OH)D concentrations in the whites were significantly related to lower BDI, STAI, PSS, and CMHS-cynicism subscale (p-values < 0.05); 25(OH)D concentrations in the blacks were only inversely associated with CMHS and most CMHS subscales (p-values < 0.05), but not with BDI, STAI and PSS. We present novel findings of consistent inverse relationships between serum 25(OH)D concentration and various measures of mental health and life stress. Long-term interventional studies are warranted to investigate the roles of vitamin D supplementation in prevention and mitigation of depression, anxiety and psychological stress in young adults.

There is robust evidence that major depression (MDD) is accompanied by a low-grade activation of the immune-inflammatory response system, which is involved in the pathophysiology of this disorder. It is also becoming apparent that glia cells are in reciprocal communication with neurons and orchestrate various neuromodulatory, homeostatic, metabolic, and immune mechanisms and have a crucial role in neuroinflammatory mechanisms in MDD. Those cells mediate the central nervous system (CNS) response to systemic inflammation and psychological stress, but at the same time, they may be an origin of the inflammatory response in the CNS. The sources of activation of the inflammatory response in MDD are immense, however, in recent years, it is becoming increasingly evident that the gastrointestinal tract with gut-associated lymphoid tissue (GALT) and increased intestinal permeability to bacterial LPS and food-derived antigens contribute to activation of low-grade inflammatory response with subsequent psychiatric manifestations. Furthermore, an excessive permeability to gut-derived antigenic material may lead to subsequent autoimmunities which are also known to be comorbid with MDD. In this chapter, we discuss fascinating interactions between the gastrointestinal tract, increased intestinal permeability, intestinal microbiota, and glia-neuron crosstalk, and their roles in the pathogenesis of the inflammatory hypothesis of MDD. To emphasize those crucial intercommunications for the brain functions, we propose the term of microbiota-gut-immune-glia (MGIG) axis.

Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), play a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown.Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP) and sulfhydryl (-SH) groups in Depression due to TLE (n=25); Anxiety Disorders due to TLE (n=27); Psychotic Disorder due to TLE (n=25); “pure TLE” (n=27); and healthy controls (n=40).TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899) and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, whilst increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels.These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups play a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology, psychosis, as well as negative and depressive symptoms.

Growth-regulating factor (GRF) is a plant-specific transcription factor family, which is involved in nearly all of the central developmental processes in plants. However, little is known about GRF family genes in cultivated sunflower. In this study, 17 GRF genes were identified and characterized from sunflower genome. Their gene structures, conserved motifs, chromosomal distributions and phylogenetic relationships were analyzed. The expression patterns of these genes were detected in various tissues of sunflower inbred line SK02R, which revealed that the 10 seed-specific GRF genes may play important roles during seed development in sunflower. Additionally, transcripts changes of the GRFs under two major abiotic stresses and phytohormones showed that most of the detected GRFs were reduced significantly by GA3 treatment, and other treatments(ABA, NaCl and PEG6000) differently regulated various sunflower growth-regulating factors at different time points. MiR396 target analysis indicated that there may exist a complicated homeostasis between miR396 and its targets GRF and WRKY transcription factor genes in cultivated sunflower. The phylogenetic and expression analyses of the GRF gene family in sunflower would be useful for further cloning and function exploration of the HaGRF genes.

Premenstrual syndrome (PMS) frequently occurs in women of childbearing age. There are different case definitions of PMS, one proposed by the American College of Obstetricians and Gynecologists (ACOG) and another based on the Daily Record of Severity of Problems (DRSP) scores. Here we review our recent papers indicating that the discovery of biomarkers of menstrual cycle-related symptoms is strongly dependent on the case definitions used and that the gold standard methods used to asses PMS, including the ACOG case definition, induce a high degree of false-negative findings. We propose a new case definition of the menstrual cycle-associated syndrome (MCAS), which is characterized by increased DRSP scores during the menstrual cycle and additionally by an exaggerated increase in symptoms the week prior to the menses. This case definition performed well and was externally validated by diverse biomarkers including plasma levels of progesterone and estradiol, chemokines (e.g. CCL2, CCL5 and CCL11), epidermal growth factor, hydroperoxides, paraoxonase 1 activity and complement C4. In conclusion, when evaluating menstrual cycle-related symptoms and their associations with biomarkers, we propose to assess daily measurements of the DRSP and based on those scores to a) use the diagnosis of MCAS as an indicant of menstrual cycle-related symptoms; and b) examine the associations of the time series in the DRSP and its subdomains (e.g. depression, physio-somatic, anxiety) and those in biomarkers including distributed lag models.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). The replication rate generates a high polyprotein integration that can contribute to ER stress. Therefore, the host cell can develop an Unfolded Protein Response (UPR) to this protein accumulation which will stimulate appropriate cellular responses in the infectious context (Adaptation, autophagy or cell death). These different stress responses can help to overcome the virus and usually support antiviral strategies initiated by infected cells. In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in epithelial A549 cells with a special focus on the causal factors behind it. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway but surprisingly without activation of the ATF6 branch. When we examined the effects of modulating the ER stress response we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV can altered the UPR in order to escape to the host cell defense system.

Redox regulation and oxidative stress have become areas of major interest in spermatology. Alteration of redox homeostasis is recognized as a significant cause of male factor infertility and is behind the damage that spermatozoa experience after freezing and thawing or conservation in a liquid state. While for a long time, oxidative stress was just considered an overproduction of ROS, nowadays it is considered as a consequence of redox deregulation. Many essential aspects of spermatozoa functionality are redox regulated, with reversible oxidation of thiols in cysteine residues of key proteins acting as an “on-off” switch controlling spermatic function. However, if deregulation occurs, these residues may experience irreversible oxidation and oxidative stress leading to spermatic malfunction and ultimately death. Stallion spermatozoa are “professional producers” of ROS due to their intense mitochondrial activity, and thus sophisticated systems to control redox homeostasis are also characteristic of this species. As a result, combined with the fact that embryos can easily be collected in this species, horses are a good model for the study of redox biology in the spermatozoa and its impact on the embryo.

Beta-thalassemia major (β-TM) patients are treated with repeated blood transfusions, which may cause iron overload (IO), which in turn may induce immune aberrations. Patients with β-TM have an increased risk of major depressive disorder (MDD). The aims of the present study are to examine whether repeated blood transfusions, IO and immune-inflammatory responses are associated with MDD in children (6-12 years) with β-TM. The Children’s Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%) and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in β-TM with (n=54) and without (n=57) MDD and in healthy children (n=55). The results show that MDD in β-TM is associated with a greater number of blood transfusions, increased IO and IL-1β levels. Partial Least Squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, IO, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of IO on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by IO and the path from IO to immune activation. IO is also associated with increased IL-10 and lower CCL11 levels but these alterations are not significantly associated with MDD. In conclusion, blood transfusions may be causally related to MDD in β-TM children and their effects are in part mediated by increased IO and the consequent immune-inflammatory response. The results suggest that not only IO and its consequences including inflammation and ferroptosis, but also other factors related to the number of transfusions may cause MDD including psychosocial stressors. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate IO and immune-inflammatory responses and to prevent MDD is children with β-TM undergoing blood transfusions.

Metal hyperaccumulating plants should have extremely efficient defence mechanisms, enabling growth and development in a polluted environment. Brassica species are known to display hyperaccumulation capability. Brassica juncea (Indiana mustard) v. Malopolska plants were exposed to trace elements, i.e., cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn), at a concentration of 50 M and were then harvested after 96 hours for analysis. We observed a high index of tolerance (IT), higher than 90%, for all B. juncea plants treated with the four metals, and we showed that Cd, Cu, Pb and Zn accumulation was higher in the above-ground parts than in the roots. We estimated the metal effects on the generation of reactive oxygen species (ROS) and the levels of protein oxidation as well as on the activity and gene expression of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). The obtained results indicate that organo-specific ROS generation was higher in plants exposed to essential metal elements (i.e., Cu and Zn), compared with non-essential ones (i.e., Cd and Pb), in conjunction with SOD, CAT and APX activity and expression at the level of encoding mRNAs and existing proteins. In addition to the potential usefulness of B. juncea in the phytoremediation process, the data provide important information concerning plant response to the presence of trace metals.

In various models of chronic kidney disease, the amount and localization of Cx43 in the nephron is known to increase, but the intracellular pathways that regulate these changes have not been identified. Therefore, we proposed that: "In the model of renal damage induced by infusion of angiotensin II (AngII), a RhoA/ROCK-dependent pathway, is activated and regulates the abundance of renal Cx43”. In rats, we evaluated: 1) the time-point where the renal damage induced by AngII is no longer reversible; and 2) the involvement of a RhoA/ROCK-dependent pathway and its relationship with the amount of Cx43 in this irreversible stage. Systolic blood pressure (SBP) and renal function (urinary protein/urinary creatinine: Uprot/UCrea) were evaluated as systemic and organ outcomes, respectively. In kidney tissue, we also evaluated: 1) oxidative stress (amount of thiobarbituric acid reactive species), 2) inflammation (immunoperoxidase detection of the inflammatory markers ED-1 and IL-1β), 3) fibrosis (immune detection of type III collagen; Col III) and 4) activity of RhoA/ROCK (amount of phosphorylated MYPT1; p-MYPT1). The ratio Uprot/UCrea, SBP, oxidative stress, inflammation, amount of Cx43 and p-MYPT1 remained high 2 weeks after suspending AngII treatment in rats treated for 4 weeks with AngII. These responses were not observed in rats treated with AngII for less than 4 weeks, in which all measurements returned spontaneously close to the control values after suspending AngII treatment. Rats treated with AngII for 6 weeks and co-treated for the last 4 weeks with Fasudil, an inhibitor of ROCK, showed high SBP but did not present renal damage or increased amount of renal Cx43. Therefore, renal damage induced by AngII correlates with the activation of RhoA/ROCK and the increase in Cx43 amounts and can be prevented by inhibitors of this pathway.

This paper attempts to clarify an long-standing issue about the number of unknowns in the Reynolds-Averaged Navier-Stokes equations (RANS). This study shows that all perspectives regarding the numbers of unknowns in the RANS stem from the misinterpretation of the Reynolds stress tensor. The current literature consider that the Reynolds stress tensor has six unknown components; however, this study shows that the Reynolds stress tensor actually has only three unknown components, namely the three components of fluctuation velocity. This understanding might shed a light to understand the well-known closure problem of turbulence.

Flavonoids are major secondary metabolites in plants, which play important roles in maintaining the cellular redox balance in cells. Chalcone synthase (CHS) is the key enzyme in the flavonoids biosynthesis pathway, and has been proved to monitor the changes to drought stress tolerance. In this work, we overexpressed a CHS gene in tobacco (Nicotiana tabacum). The transgenic tobacco plants were more tolerant than the control plants to drought stress. The transcription levels of the key genes involved in the flavonoids pathway and the contents of seven flavonoids were also significantly raised in the transgenic tobacco plants. In addition, overexpression of the CHS gene lead to a lower concentration of the oxidative stress product malondialdehyde. Overall, the NtCHS gene studied in this work was considered as a candidate gene for genetic engineering to enhance drought tolerance of plants and improve response to oxidative stress.

Scarcity of water is one of the most serious concerns in plant biology with diverse implications at all the levels of molecular, biochemical, and physiological phenomena of plant growth, development, and consequently the productivity. Most of the strategies to induce or enhance drought tolerance in plants are unreasonably expensive and/or time-consuming. Some studies conducted in the recent past have shown that plant growth regulators (PGRs) may induce/improve physiological tolerance in plants to cope with adverse environmental conditions including drought. The present study was aimed at investigating the effects of foliar spray of GABA (0, 1, 2, and 4 mM) applied 20 days following the germination of seeds, on vegetative growth, morphological characteristics, integrity of cell-membrane, and the levels of photosynthetic pigments and enzymatic antioxidants in carrot cvs. Supertaj and Bharat, grown under 100% and 50% field capacity of soil moisture. The treated and untreated (control) carrot plants were harvested and analyzed 2 weeks following the GABA application. The results revealed that foliar application of GABA improved the vegetative growth and significantly increased the levels of free amino acids, plastid pigments, enzymatic antioxidants, and the relative water content in the root crop grown under 50% field capacity of soil moisture, compared to control. Additionally, the GABA application decreased the electrolyte leakage of ions and melondialdehyde (MDA) content in carrot leaves. The carrots harvested from GABA-treated or untreated (control) plants were not significantly different for their protein contents. In conclusion, the incorporation of GABA in the production management of carrots may help plants to mitigate the adverse effects of water deficit stress.

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rβ, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes’ gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

Chronic heat stress (HS), aggravated by global warming, reduces the production efficiency of the buffalo dairy industry. Here, we conducted a proteomic analysis to investigate the adaptation strategies used by buffalo in response to heat stress. Seventeen differentially abundant proteins with known functions were detected using label-free quantification (LFQ), and five of these differentially expressed proteins were validated with parallel reaction monitoring (PRM). These five proteins were associated with various aspects of heat stress, including decreased heat production, increased blood oxygen delivery, and enhanced natural disease resistance. Lipase (LPL), glutathione peroxidase 3 (GPX3), cathelicidin-2 (CATHL2, LL-37), ceruloplasmin (CP), and hemoglobin subunit alpha 1 (HBA1) were shown to play cooperative roles in the tolerance of chronic HS in dairy buffalo. We found that high levels of HBA1 increased blood oxygen transport capacity. Our results increase our understanding of the adaptation of dairy buffalo to chronic heat stress.

The tremendous diversity and complexity of proteins invariably results in protein misfolding, to which cells have evolved numerous mechanisms of mitigating. Degrading misfolded proteins is perhaps the most intuitive strategy, but also critical to managing proteostasis are the elaborate mechanisms of translational control. Attenuated rates of translation ameliorate protein misfolding by downregulating the flux of new protein and conserving ATP. Loss of translational control, particularly in neurons, constitutes a major proteostatic dysfunction capable of causing or exacerbating neurodegeneration, while interventions aimed at downregulating protein synthesis are generally neuroprotective. In this review, I examine the critical neuronal signaling networks employed to control translation with an emphasis on current research. This includes the Unfolded Protein Response (UPR), the mitochondrial UPR (mtUPR), mTORC1 signaling, and stress granule formation.

This paper attempts to clarify an issue regarding the lasting unsolved problem of turbulence, namely the closure problem. This study shows that all perspectives regarding the numbers of un- known quantities in the Reynolds turbulence equations stem from the misunderstandings of physics of the Reynolds stress tensor. The current literatures have a consensus that the Reynolds stress tensor has six unknowns; however, this study shows that the Reynolds stress tensor actually has only three ones, namely the three components of fluctuation velocity. With this new understanding, the closed turbulence equations for incompressible flows are proposed.

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by N-nitro L-arginine methyl ester (L-NAME) in rats. Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg); L-NAME plus hesperidin (15 mg/kg), or hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in L-NAME rats. Moreover, hesperidin or captopril alleviated L-NAME-induced cardiac remodeling; increases in wall thickness, cross sectional area (CSA) and fibrosis of left ventricular (LV), and vascular remodeling; increases in wall thickness, CSA, vascular smooth muscle cells and collagen deposition in the aorta. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1) and enhancing plasma nitric oxide metabolite (NOx) in L-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF-β1 protein expression and the over-expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were suppressed in L-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in L-NAME hypertensive rats. The possible mechanism may involve its antioxidant and anti-inflammatory effects.

Radical oxygen species formed in human tissue cells by many endogenous and exogenous pathways, cause extensive oxidative damage, which has been linked to various human diseases. This review paper provides an overview of lipid peroxidation and focuses on the free-radicals initiated processes of LDL oxidative modification and DNA oxidative damage, which are widely associated to the initiation and development of atherosclerosis and carcinogenesis, respectively. The article subsequently provides an overview of the recent human trials or even in vitro investigations on the potential of natural antioxidant compounds (such as carotenoids, vitamins C and E) to monitor LDL and DNA oxidative changes.

In this study, the model proposed by Yang et al. to generalize the stress–strain model for unconfined concrete with consideration of the size effect is expanded. Sim et al.’s compressive strength model that is based on the function of specimen width and aspect ratio was used for the maximum stress. In addition, a strain at the maximum stress was formulated as a function of compressive strength by considering the size effect using the regression analysis of datasets compiled from a wide variety of specimens. The descending branch after the peak stress was formulated with consideration of less dissipated area of fracture energy with the increase in specimen width and aspect ratio in the compression damage zone (CDZ) model. The key parameter for the slope of the descending branch was formulated as a function of specimen width and aspect ratio, concrete density, and compressive strength of concrete considering the size effect. Consequently, a rational stress–strain model for unconfined concrete was proposed. This model explains the trends of the peak stress and strain at the peak stress to decrease and the slope of the descending branch to increase, as the specimen width and aspect ratio increase. The proposed model agrees well with the test results, irrespective of the compressive strength of concrete, concrete type, specimen width and aspect ratio. In particular, the proposed model for the stress–strain curve rationally considered the effect of decreasing peak stress and increasing the descending branch slope, with the increase in specimen width and aspect ratio.

Carbon fiber reinforced polymer (CFRP) has been used widely in strengthening of steel structures. Steel/CFRP systems subjected to elevated temperatures is realistic in a summer climate event in many countries where the temperature in steel may approach 50 °C or even higher, which will lead to the degradation of the bond performance between CFRP and steel. Therefore, predicting the bond behavior of the CFRP/steel system under elevated temperature is critical. This paper investigated the mechanical performance of CFRP/steel adhesively-bonded double strap joints at elevated temperatures. Thirty CFRP-steel double strap joints were tested to failure under temperatures between 10 °C and 90 °C. It was found that the joint failure mode changed from adherend failure to debonding failure as the temperature approached T_g. In addition, the ultimate load and joint stiffness decreased significantly at temperatures near to and greater than T_g. Based on the experimental results, a model is proposed to predict the bond stress of the CFRP/steel at different temperatures.

This paper shown that turbulence closure problem is not an issue at all. All mistakes in the literature regarding the numbers of unknown quantities in the Reynolds turbulence equations stem from the misunderstandings of physics of the Reynolds stress tensor, i.e., all literatures have stated that the symmetric Reynolds stress tensor has six unknowns; however, it actually has only three unknowns, i.e., the three components of fluctuation velocity. We shown the integral-differential equations of the Reynolds mean and fluctuation equations have exactly eight equations, which equal to the numbers of quantities in total, namely, three components of mean velocity, three components of fluctuation velocity, one mean pressure and one fluctuation pressure. That is why we claim in this paper, that the Reynolds Navier-Stokes turbulence equations of incompressible flow are closed rather than unclosed. This study may help to solve the puzzle that has eluded scientists and mathematicians for centuries.

The role of epigenetic alterations in the pathogenesis of age-related macular degeneration (AMD) has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may restore changes in LINE-1 methylation by modulating DNMTs and SIRT1 functions. Cells were treated with 25 mU/ml glucose oxidase (GOx) or 10 µg/ml lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b and SIRT1 expression (p-values <0.05), as well as total DNMTs (-28.5%; p<0.0001) and SIRT1 (-29.0%;p<0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values<0.05), as well as total DNMTs (-14.9%;p=0.007) and SIRT1 (-20.1%;p<0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values<0.0001). We also demonstrated that treatment with 10 μM resveratrol for 24 hours counteracted the detrimental effect on LINE-1 methylation via increasing DNMTs and SIRT1 functions in cells upon oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of AMD.

The study aimed to investigate the effects of colonization with two arbuscular mycorrhizal (AM) fungi, Funneliformis mosseae , Diversispora versiformis , alone and in combination on the growth and nutrient acquisition of NaCl-stressed Chrysanthemum morifolium (Hangbaiju) plants in the greenhouse experiment. Mycorrhizal and non-mycorrhizal Hangbaiju plants were grown under different salinity levels imposed by 0, 50 and 200 mM NaCl for five months, following 6 weeks of non-saline pre-treatment. The results showed that root length, shoot and root dry weight, total dry weight, shoot and root N concentration were higher in mycorrhizal than in non-mycorrhizal plants under moderate saline conditions especially with D. versiformis colonization. As salinity increased, the mycorrhizal colonization, the mycorrhizal dependence (MD) decreased. Enhancement of tissue N acquisition is probably the main mechanism underlying salt tolerance in AM plants. It is suggested that the symbiotic associations between D. versiformis fungus and C. morifolium plants may be taken as a biotechnological practice in culture.

As professionals, social workers have a special position in relation to considering the needs of children with cancer and their families. Hence, it is important to recognize the experiences and challenges of social workers to improve care of their clients. This study was a qualitative content analysis that aimed to determine a comprehensive understanding of 19 pediatric oncology social workers’ experiences in Iran. Data were collected using semi structured interviews and field observations, analyzed through face content analysis. Concepts extracted from social workers’ experiences consisted of the nature of oncology work, lack of professional competence, low organizational support and professional inferiority that were related to main concept of "exhausting and stressful service". The results indicated that social workers' involvement in stressful and emotionally demanding situations and professional and organizational challenges caused personal exhaustion. In addition to explaining the social workers’ experiences and related factors, the results emphasize the importance of taking care of service providers to prevent them becoming stressed and exhausted. It is also important to protect patients from the consequences of stressed and exhausted care providers so further research is recommended to develop specific intervention.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.

This paper presents an analytical method for determining the bending stresses and deformations in prismatic noncircular profile shafts with trochoidal cross sections. The so-called higher trochoids can be used as form-fit shaft–hub connections. Hybrid (mixed) higher trochoids (M-profiles) were proposed in [1] and adapted to a practical industrial application in [2]. M-profiles combine the advantages of standardised polygon (DIN 32711 [3]) and spline (DIN 5486 [4]) contours used as shaft–hub connections for the transmission of torsional loads. In this study, the geometric and mechanical properties of the higher hybrid trochoids were investigated using complex functions to simplify the calculations. The pure bending stress and shaft deflection were determined for M-profiles using the bending theory formulated by Muskhelishvili [5]. The loading cases consisted of static and rotating bends. Analytical, numerical, and experimental results agreed well.

There are many ‘faces’ of early life adversity (ELA), such as childhood trauma, institutionalization, abuse or exposure to environmental toxins. These have been implicated in the onset and severity of a wide range of chronic non-communicable diseases later in life. The later-life disease risk has a well-established immunological component. This raises the question as to whether accelerated immune-ageing mechanistically links early-life adversity to the lifelong health trajectory resulting in either ‘poor’ or ‘healthy’ ageing. Here we examine observational and mechanistic studies of ELA and inflammageing, highlighting common and distinct features in these two life stages. Many biological processes appear in common including reduction in telomere length, increased immuno-senescence, metabolic distortions and chronic (viral) infections. We propose that ELA shapes the developing immune, endocrine and nervous system in a non-reversible way, creating a distinct phenotype with accelerated immuno-senescence and systemic inflammation. We believe that ELA acts as an accelerator for inflammageing and age-related diseases. Furthermore, we now have the tools and cohorts to be able to dissect the interaction between early life adversity and later life phenotype. This should, in the near future, allow us to identify the ecological and mechanistic processes that are involved in ‘healthy’ or accelerated immune-ageing.

Recent advancements in molecular diagnostics have highlighted the potential of circulating cell-free DNA (ccfDNA) as a biomarker in various diseases. This study aims to explore the role of ccfDNA in the early diagnosis, prognosis, and therapeutic monitoring of diseases, with a focus on oncology. We conducted a comprehensive review and analysis of current literature, combined with experimental approaches involving advanced genomic sequencing and bioinformatics techniques. Our research systematically characterizes the molecular composition of ccfDNA, including its origins, size distribution, and methylation patterns, across different disease states. Furthermore, we investigate the dynamics of ccfDNA release and clearance in the bloodstream, elucidating mechanisms that could influence its diagnostic accuracy. In the context of cancer, we analyze the correlation between tumor-derived ccfDNA and disease progression, response to therapy, and overall survival. Our findings indicate that ccfDNA holds promise as a non-invasive biomarker for early disease detection, real-time monitoring of treatment efficacy, and potentially, predicting relapse. This study contributes to the growing field of liquid biopsies and opens new avenues for personalized medicine, emphasizing the need for standardized protocols in ccfDNA analysis to maximize its clinical utility. The implications of our findings extend beyond oncology, suggesting potential applications of ccfDNA in other pathological conditions.

Photosystem I is a key component of primary energy conversion in oxygenic photosynthesis. Electron transfer reactions in Photosystem I take place across two, parallel, electron transfer chains that converge after a few electron transfer steps, sharing both the terminal electron acceptors, that are a series of three Iron-Sulphur (Fe-S) clusters known as , and , and the terminal donor, . The two electron transfer chains show kinetic differences which are, due to their close geometrical symmetry, mainly attributable to the tuning of the physical-chemical reactivity of the bound cofactors, exerted by the protein surroundings. The factors controlling the rate of electron transfer between the terminal Fe-S clusters are still not fully understood because of the difficulties of monitoring these events directly. Here we present a discussion concerning the driving forces associated to electron transfer between and as well as and , employing a tunnelling-based description of the reaction rates coupled to the kinetic modelling of forward and recombination reactions. It is concluded that the reorganisation energy for oxidation shall be lower than 1 eV. Moreover, it is suggested that the analysis of mutants with altered redox properties can also provide useful information concerning the upstream, phylloquinone, cofactor energetics.

This paper, based on the "Unified Theory of Forces," rigorously proves the formula of de Broglie's wave function. This helps us better understand the following important issues: 1) Theoretically prove and understand the essence of de Broglie's wave function; 2) Prove that when the particle's momentum P is determined, the greater the mass of the particle, the more concentrated its wave function distribution, and the weaker the interference effect; 3) Correct the spatial distribution of the wave function of free particles, proving that the wave function of free particles is strictly constrained within a finite spatial range, which is consistent with the facts we observe.

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of cortical neurodevelopment, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth, explaining the spatial organization and functional significance of neuron response preferences, and compatible with features of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations provide a preliminary anatomically realistic model of cortical information processing.

In Korea, the underground silo structure for low- and intermediate-level radioactive waste disposal facilities has been constructed and operated since 2014. Large-scale earthquakes occurred in 2016 and 2017, respectively, in Gyeongju and Pohang areas near the underground silo structures, and interest in the stability of the underground silo increased significantly. In this paper, one-dimensional free field analyses have been carried out before the three-dimensional silo dynamic analyses subjected to earthquake loadings. As an additional study, a new form of finite element equilibrium equation is derived in terms of relative motions, which is essentially the same equation as that expressed in terms of total motions where the base shear force is applied for earthquake load. The accuracy of conventional finite element solutions is evaluated by directly comparing them with closed-form solutions by frequency domain analysis such as SHAKE91.

Background: The proven efficacy of mTOR inhibitors (mTORI), tyrosine kinase inhibitors (TKI) or immune checkpoint inhibitors (ICI) therapies in metastatic renal cell carcinoma (RCC), suggested that these agents should be investigated as adjuvant therapy with the aim of eliminating any residual undetectable microscopic disease after curative resection. Our study aimed to compare the efficacy of these treatments through the application of an innovative method that reconstructs individual patient data. Methods: Nine phase III studies describing different treatment options for adjuvant RCC were selected. Individual patient data were reconstructed from Kaplan–Meier (KM) curves through the “IPDfromKM method”. Disease-free survival (DFS) were compared among combination treatments and control arm (placebo). Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, this study showed that two ICIs (pembrolizumab and nivolumab plus ipilimumab) and one TKI (sunitinib) showed superiority over placebo, whereas both TKI and mTORI did not. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown.. Conclusion: This novel approach to investigating survival has allowed us to conduct all of the indirect head-to-head comparisons between these agents in a context where no "real" comparative trials have been conducted.

This paper introduces new improvements to the modified version of the BIRECT (BI secting RECTangles) algorithm referred to as BIRECTv. We explore various approaches, by first including a grouping strategy for hyper-rectangles having almost the same sizes by categorizing them into different classes. Therefore constraining them not to exceed a certain pre-defined threshold (a small positive value to define the tolerance level). This approach allows for more efficient computation and can be particularly useful when dealing with a large number of hyper-rectangles with varying sizes. To avoid over-sampling, and preventing redundant or excessive sampling, at some shared vertices in descendant subregions, a particular vertex database is used to limit the number of samples taken within each subregion to two. The experimental investigation shows that these improvements have a positive impact on the performance of the BIRECTv(imp.) algorithm and the proposal is a promising global optimization algorithm compared to the original BIRECTv algorithm and its variants. Additionally, the BIRECTv(imp.) algorithm showed particular efficacy in solving high-dimensional problems.

Objectives: This study aimed to assess the impact of a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis from a single center between 2015 to 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features and Gleason score (GS). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. using the Kaplan-Meier survival function and Cox regression model were assessed. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after curative prostatectomy were 5%, 13%, and 21%, respectively. The survival analysis showed that adverse MRI features as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GS≥8, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE- and GS &lt;(4+4)) the presence of adverse MRI features, has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision-making; mECE+, TCCL, capsular disruption, and GS≥8 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who would benefit from closer monitoring.

In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.

One-Dimensional Solar Cell Capacitance Simulator (1D-SCAPS) and n-i-p planar configuration have been employed for the simulation of the caesium tin iodide (CsSnI₃)-based perovskite solar cell (PSC) with titanium (IV) oxide (TiO₂) and copper thiocyanate (CuSCN) as the electron and hole transport materials respectively. The results obtained for the initially modeled PSC compared well with similar devices in the literature but marred with high recombination rate. As such, the defect density in the CsSnI₃ absorber was varied from 10¹³ cm^-3 to 10¹⁷ cm^-3 and enriched with SnCl₂ (additive) and Br⁻(dopant) respectively. This strategy ensured a reduced concentration of Sn⁴⁺ vacancy (V_Sn) in the CsSnI₃ absorber with improved carrier lifetime and diffusion length beyond 0.05 ns and 1.1µm by a magnitude of the order of 10³ and 10² respectively for the enriched CsSnI₃ –based PSC. For the optimized PSC, we recorded V_OC=1.289 V, J_SC=32.60 mA.cm^-2, FF=83.56% and PCE=35.12%.

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) enables determination of room-temperature structures without causing radiation damage. Using an optical pump-probe or mix-and-injection, SFX enables the intermediate state visualization of a molecular reaction. In SFX experiments, serial and stable microcrystal delivery to the X-ray interaction point is vital for reasonable data collection and efficient beam time. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) facility established SFX instruments at a nanocrystallography and coherent imaging (NCI) experimental station. Various sample delivery methods, including injection, fixed-target scanning, and hybrid methods, have been developed and applied to collect XFEL diffraction data. Herein, we review the currently available sample delivery methods for SFX at the NCI experimental station at the PAL-XFEL. This article will help PAL-XFEL users access the SFX system for their experiments.

Tapping panel dryness (TPD) syndrome is a complex disease of Rubber tree (Hevea brasiliensis L.) which causes cessation of latex drainage upon tapping of rubber tree. Rubber tree virus (RTV1) was identified as a novel pathogen associated with rubber tree and a potential causal agent of TPD. RTV1 is a monopartite RNA virus that is linear, non-enveloped and has a single-stranded (ss) positive RNA genome of approximately 6081 nucleotides and is composed of two major open reading frames (ORFs), ORF1 (polyprotein), and ORF2 (movement protein. This study aimed to investigate the possibility of rubber genome encoded tree microRNAs (miRNAs) as novel therapeutic targets against RTV1 using in silico algorithms. Mature rubber tree miRNAs are retrieved from the miRBase database and are used for hybridization of RTV1 using five different five different computational algorithms including miRanda, RNA22, RNAhybrid and psRNATarget. A total of eleven common rubber tree miRNAs were identified based on consensus genomic positions. The consensus of four algorithms predicted the hybridization sites of hbr-miR396a and hbr-miR398 at common locus positions 6676, 1840 respectively. To validate the prediction, secondary structures of the consensual rubber tree miRNAs and free energy of duplex binding were calculated using the RNAfold and RNAcofold algorithms respectively. We created a plot between rubber tree miRNAs and RTV1 ORFs by using Circos algorithm. In this study, we predicted eleven consensual rubber tree miRNAs. Among these miRNAs, hbr-miR398 was identified as the most effectual miRNA that may target the ORF1 gene of the RTV1 genome. The predicted data will be important in the development of rubber trees resistant to RTV1.

A facile and novel synthesis of thirteen 2-amino-3-cyanopyridine derivatives 5(a-m), by a one-pot multicomponent reaction (MCRs), is described for the first time, starting from aromatic aldehydes, malononitrile, methyl ketones, or cyclohexanone and ammonium acetate in the presence of the nanostructured diphosphate Na2CaP2O7 (DIPH) at 80 °C, under solvent-free conditions. These compounds were synthesized in short reaction times with good to excellent yields (84-94%). The diphosphate Na2CaP2O7 is used as an efficient catalyst, environmentally, easy handling, non-toxic, stable, and reusable. Our study was strengthened by the synthesis of five new pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by intramolecular cyclization of 2-amino-3-cyanopyridines 5(b, c, g, h, j), with formamide. The synthesized products were characterized by FT-IR, SEM, XRD, TEM, 1H NMR, 13C NMR, TLC, and BET. The operating conditions were optimized using a model reaction in which the catalyst amount, temperature, time, and solvent effect were evaluated. The antibacterial activity was tested against Gram-positive and Gram-negative strains for the synthesized compounds.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

This article presents, for the first time, the kinetics and the general conversion features of a 3-component system, BT(BC)/iodonium/Amine, based on proposed mechanism of Liu et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using the new multi-functional initiator of benzophenone–triphenylamine (BT). The additives, iodonium and EDB, have the dual function of (i) regeneration BT and (ii) produce of extra radicals for improved FRP and CP. Analytic formulas are developed to explore the new features including: (i) the conversion efficacy (CE) of FRP is an increasing function of the light intensity, the effective absorption coefficient, and the concentration sum of each of the components, BT, Iod, amine, for transient state. However, CE at steady-state is independent to the light intensity; (ii) the trifunctional hybrid structures of BT3 leads to larger light absorption than other types of BT; it also provides more active sites for the H-abstraction in the presence of EDB, leading to high CE; (iii) the efficacy of FRP is an increasing function of the amine (EDB) concentration, in contrast to that of CP having an opposite dependence; (iv) the consumption rate of BT3 in the BT3/ Iod/EDB system is slower than that of the BT3/Iod system due to photoredox catalytic cycle, and the larger initiator regeneration (RGE)
in the three-component system. A comprehensive model is also proposed that the CE (for both FRP and CP) is governed by (N_jK_jbI), whereas more complex formulas are developed; where Kj is an effective rate constant proportional to the electron transfer quantum yield, and the combined effects of other coupling rate constants; b is an effective absorption coefficient given by the light absorption and excited state quantum yield.

This review covers some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, and the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in {\it The Foundations of Statistics} and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called `small worlds' but cannot work in `large worlds'. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions still need to be answered in all three fields in order to make progress on these problems.

Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.

It is of merit to study the appropriate amount of fiber to add to free-range chickens feed to improve the microbial diversity and gut health in times of plant fiber deprivation. OptiCell is a useful source of fiber as a type of eubiotic lignocellulose, and its positive effects on the growth performance and laying performance of chickens has already been proven. However, few researchers have researched the effects of adding OptiCell on the gut microbiota of chickens. In this research we added three different levels of OptiCell (0%, 2% and 4%) to the feed of caged and free-range Bian chickens from September to November, aiming to observe the effects of adding OptiCell and different feeding modes on the gut microbial diversity and gut health of chickens, and aiming to determine an appropriate amount of OptiCell. The results showed that adding OptiCell could increase the thickness of the cecum mucus layer and the abundance of Akkermansia and Faecalibacterium in caged chickens, and 4% OptiCell was optimum. In addition, adding OptiCell increased the microbial diversity and the abundance of the butyrate-producing bacteria Faecalibacterium and Roseburia of fee-range chickens. The α-diversity and the length of the small intestine with 2% OptiCell in free-range chickens were better than with 2% OptiCell in caged chickens. In addition, compared with caged chickens, the free-range chickens had longer small intestine and lower GLP-1. Taken together, an appropriate amount of OptiCell benefitted the microbial diversity and health of chickens; it was necessary to add dietary fiber to the feed of free-range chickens when plant fibers was lacking, and 2% OptiCell was found to be optimum.

The current study aims to study the optimal fermentation conditions for producing microbial bioactive compounds. The microwave parameters consist on 2450 MHz, and 500-watt for 20, 30, and 40 seconds. The solubility of solvents was tested for the extraction of antioxidant compounds from fermented rice (Koji) by A. flavus, Ethyl acetate was the best solvent used for extraction purposes. Antioxidant properties were differentiated by blocking the oxidation of the linoleic acid with an inhibition rate of 73.13% at a concentration of 200 mg/mL, in addition to increasing its effectiveness for free radical extraction and reduction strength by increasing concentrations gradually. The bond ability to irons was lower compared to the EDTA-2Na, in addition to the obtained total content corresponding to phenolic compounds in the ethyl acetate extract of fermented rice (Koji) by A. flavus was 232.11 mg, on the basis of galic acid/mg. The stability of the antioxidant compounds of the ethyl acetate extract of fermented rice (Koji) by A. flavus was also studied; showing stability under neutral conditions, as well as at high temperatures (185 °C during two hours). However, no stability was obtained under acidic and alkaline conditions.

The processing of cloud free geo-referenced imagery is one of the preliminary processing step of any land application. This letter describe the methodology developed to obtain a seamless cloud free composite of Africa for 2016 using Sentinel-2A data at 10 meters resolution freely available from the European Space Agency. The method is based on an hybrid method resulting from the merging of the two most robust time series methods namely the "darkest pixel" and the "maximum NDVI" previously developed with AVHRR time series.

Drought and water scarcity are significant factors limiting the development of China's maize industry. Deep sowing, as a method to mitigate drought and preserve soil moisture and seedlings, can effectively mitigate the adverse effects of drought stress on their growth. However, deep sowing can influence the emergence of maize seedlings and has a certain impact on their growth and development. To investigate the physiological and transcriptomic changes in maize inbred lines under deep sowing stress, and the alleviation effects of exogenous hormones, this study investigated the response of mesocotyl in deep-seeding tolerant maize inbred line Qi319 and deep-seeding sensitive maize inbred line Zi330 to deep-seeding stress under exogenous MeJA treatment. The physiological and transcriptomic mechanisms underlying the alleviation of deep-seeding stress by exogenous MeJA were elucidated. Results showed that compared to normal sowing depth, mesocotyl length (MES), mesocotyl and coleoptile length (MESCOL) significantly increased under deep-seeding stress for both inbred lines, while seedling length (SDL) was significantly inhibited. However, after adding 1.5 μmol·L^-1 MeJA, MES, MESCOL, and SDL significantly increased compared to deep-seeding stress alone. Exogenous MeJA promoted cell elongation, enhanced mesocotyl length, and improved seedling emergence ability. RNA-Seq sequencing revealed differentially expressed genes (DEGs). Under deep-seeding stress compared to normal sowing depth conditions, 1248 DEGs were identified in Qi319 and 1288 DEGs were identified in Zi330. After adding exogenous MeJA under deep-seeding stress compared to normal sowing depth with exogenous MeJA treatment conditions, 538 DEGs were identified in Qi319 and 2284 DEGs were identified in Zi 330. GO enrichment analysis showed that differentially expressed genes were mainly concentrated in biological processes, cell components and molecular functions. KEGG enrichment analysis showed that differentially expressed genes were mainly concentrated in transport and catabolism, signal transduction, amino acid metabolism and lipid metabolism processes. Compared with the deep-seeded treatment, 12 differentially expressed genes were co-expressed in the two inbred lines under exogenous MeJA treatment, and 10 key genes, including ornithine decarboxylase, terpene synthase 7 and ethylene reaction transcription factor 11, were screened out. Our findings elucidate the molecular mechanism underlying maize's tolerance response to deep seeding and offer valuable insights into candidate gene resources for improving deep seeding tolerance in maize.

Mediterranean diet has been widely suggested to exert significant beneficial effects on endothelial oxida-tive status and cardiometabolic health. Greek Orthodox monasteries, due to their specific nutritionaland sartorial habits, comprise a population which strictly adheres to nutritional patterns with restricted eating and a plant-based subset of the Mediter-ranean diet, often accompanied by profound hypovitaminosis D. Time –restricted eating is also adopted from a large part of general lay Greek population for health promoting reasons, without restrictions on an-imal product consumption, as imposed by Orthodox religious fasting. However, comparative effects of these nutritional patterns on oxidative stress markers remain scarce. The present study attempted to evaluate the effects of Christian Orthodox fasting (COF) in a group of vitamin D –deficient and overweight Orthodox nuns from Central and Northern Greece, compared to the implementation of TRE, 16:8 dietary regimen in a cohort of adult women from the general population from the same region, with regard to markers of endothelial oxidative status. A group of 50 women from two Orthodox monasteries in Northern Greece and one group of 50 healthy lay women were included. During enrollment a detailed recording of dietary habits was performed, along with a scientific registry of demographic and anthropometric characteristics (via bioimped-ance).Orthodox nuns followed a typical Orthodox fasting regimen[daily feeding window (8 am–4 pm)] whereas lay women followed a TRE 16:8 regimen with the same feeding time-window with recommenda-tion to follow a low-fat diet, without characteristics of the Mediterranean diet. We included a complete biochemical analysis, as well as calciotropic profiles [Calcium-Ca, Albumin, Parathyroid hormone-PTH, 25-hydroxyvitamin D- 25(OH)D] as well as and markers of TAC (trichloroacetic acid), (glutathione) GSH and thiobarbituric acid reactive substances (TBARS) concentrations, as markers of oxidative status. All groups were comparable at baseline for calcium, PTH and 25(OH)D concentrations, with no significant differences between groups. Orthodox nuns manifested a lower median GSH compared to con-trols (6.0 vs. 7.2, p 0.04) and a higher median TAC (0.92 vs. 0.77, p <0.001). TBARS comparisons showed no significant difference between the two groups. No significant associations of oxidative status with 25(OH)D, PTH and markers of glucose homeostasis were evident. Results of this small pilot study indicate that both dietary regimens have advantages over oxidative markers compared to each other, with increased TAC in the groups of Orthodox Nuns after a 16th week period of COF compared to a 16:8 TRE and increased GSH concentrations in the lay women group. Future randomized trials are required to investigate superiority or non-inferiority between these dietary patterns, in the daily clinical setting.

The Bax inhibitor-1 (BI-1) gene family, which is required for plant growth, development, and stress tolerance, remains largely unexplored in cauliflower. In this study, we identified and characterized cauliflower BI-1 family genes. On the basis of aligned homologous sequences and collinearity with Arabidopsis genes, we identified nine cauliflower BI-1 genes, which encoded proteins that varied regarding length, molecular weight, isoelectric point, and subcellular localization (i.e., Golgi apparatus, plasma membrane, cell membrane, and chloroplast). Phylogenetic analyses detected evolutionary conservation and divergence among these genes. Ten structural motifs were identified, with Motif 5 crucial for inhibiting apoptosis. According to the cis-regulatory elements in their promoters, these genes likely influence hormone signaling and stress responses. Expression profiles among tissues highlighted the diversity in the functions of these genes, which were significantly expressed in the silique and root. Focusing on BobBIL4, we investigated its role in brassinosteroid (BR)-mediated root development and salt stress tolerance. BobBIL4 expression levels increased in response to BR and salt treatments. The functional characterization of this gene in Arabidopsis revealed it enhances root growth and salinity tolerance. These findings provide insights into BI-1 gene functions in cauliflower, while also highlighting the potential utility of BobBIL4 for improving crop stress resistance.

The neuronal etiology of obesity is centered around diet-induced inflammatory state in the arcuate nucleus of the hypothalamus which impairs the functionality of pro-opiomelanocortine neurons (POMCs) responsible for whole-body energy homeostasis and feeding behavior. Intriguingly, systemic salt inducible kinase 2 (SIK2) knockout mouse demonstrated reduced food intake and energy expenditure along with modestly dysregulated metabolic parameters suggesting a causal link between the absence of SIK2 activity in POMCs and the observed phenotype. To test this hypothesis, we conducted a comparative secretomics study from POMC neurons following pharmacologically induced endoplasmic reticulum (ER) stress induction, a hallmark of metabolic inflammation and POMC dysregulation in diet induced obese (DIO) mice. Our data provide significant in vitro evidence for the POMC specific SIK2 activity in controlling the energy metabolism and feeding in DIO mice by regulating the nature of related POMC secretome. Our data also suggests that under physiological stress conditions SIK2 may act as a gatekeeper for the secreted inflammatory factors and signaling molecules critical for cellular survival and energy homeostasis. On the other hand, in the absence of SIK2 gate opens leading to surge of inflammatory cytokines and apoptotic cues concomitant with the dysregulation of POMC neurons.

Submergence stress challenges direct seeding in rice cultivation. In this study, we identified a heat shock protein, NAL11, with a DnaJ domain, which can regulate the length of rice coleoptiles under flooded conditions. Through bioinformatics analyses, we identified cis-regulatory elements in its promoter, making it responsive to abiotic stresses, such as hypoxia or anoxia. Expression of NAL11 was higher in the basal regions of shoots and coleoptiles during flooding. NAL11 knockout triggered the rapid accumulation of abscisic acid (ABA) and reduction of Gibberellin (GA), stimulating rice coleoptile elongation and contributes to flooding stress management. In addition, NAL11 mutants were found to be more sensitive to ABA treatments. Such knockout lines exhibited enhanced cell elongation for coleoptile extension. Quantitative RT-PCR analysis revealed that NAL11 mediated the gluconeogenic pathway, essential for the energy needed in cell expansion. Furthermore, NAL11 mutants reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde under submerged stress, attributed to an improved antioxidant enzyme system compared to the wild-type. In conclusion, our findings underscore the pivotal role of NAL11 knockout in enhancing the tolerance of rice to submergence stress by elucidating its mechanisms. This insight offers a new strategy for improving resilience against flooding in rice cultivation.

Background and aim: Apigenin (API), a dietary flavone subclass of flavonoid found in herbs, fruits, and vegetables, exhibits various pharmacological effects. However, its role in triggering oxidative stress- induced apoptosis in uterine cells remains unclear. This study aimed to evaluate the oxidative stress-mediated apoptosis induced by apigenin in rat uterine leiomyoma ELT3 cells. Material and methods: ELT3 cells were treated with 50 and 100 µM API for 48 hours. We assessed oxidative stress markers (reactive oxygen species, malondialdehyde), antioxidant defense (glutathione reductase activity), cell proliferation, and apoptotic gene expression (p53, Bax, Bcl-2, caspase-3, caspase-9) using relevant assays and real-time PCR. Results: API treatment decreased cell proliferation and glutathione reductase activity in ELT3 cells. This coincided with increased levels of reactive oxygen species, malondialdehyde, and lactate dehydrogenase activity, indicating oxidative stress and cell damage. Furthermore, apigenin upregulated pro-apoptotic genes (p53, Bax, caspase-3, caspase-9) and downregulated the anti-apoptotic gene Bcl-2, suggesting activation of the intrinsic apoptotic pathway. Conclusion: API induces apoptosis in rat uterine leiomyoma cells through a mechanism involving oxidative stress-mediated activation of the intrinsic apoptotic pathway.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder characterized by difficulty maintaining attention, impulsivity and hyperactivity. Although the cause of this disorder is still unclear, recent studies state that heredity is important in the development of ADHD. This is linked to a few comorbidities: depression, criminal behavior and anxiety. Although genetic factors play a major role in the pathogenesis of ADHD, there are also non-genetic factors, one of which would be oxidative stress (OS) that are associated with ADHD. OS is implicated in the pathogenesis of ADHD, through lower levels of antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), as well as a lower total antioxidant status (TOS) compared to control groups. Moreover, there is a close bidirectional connection between the nervous system and the intestinal microbiota, and the communication between the two systems is carried out through the gut-brain axis (GBA). A thorough review of diet, OS implications, mechanism of action, pharmacokinetics, and drug-drug interactions are reviewed here, with a special focus on treatment in adults with comorbid conditions.

Background: Glutathione and its related enzymes constitute one of the most important antioxidant defense mechanisms against oxidative stress and cancer formation in the body. Bladder cancer is the second most common urological malignancy after prostate cancer. Oxidative stress plays a significant role in the development and prognosis of bladder cancer. The aim of this study was to examine the effect of glutathione on the prognosis of non-muscle-invasive bladder cancer. Methods: The 98 patients with bladder tumors were those with T1G3 pathology who had undergone intravesical Bacillus Calmette-Guérin therapy, while the 30 controls were healthy individuals with no history of transitional cell carcinoma of the bladder. The 128 participants were divided into four groups: Group 1 comprised 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, Group 3 consisted of 29 patients who progressed to muscle-invasive stages, and Group 4 was composed of 30 healthy volunteers. Blood samples were collected from all participants. Glutathione levels were measured, and statistical analysis were performed. Results: There was a statistically significant difference in reduced glutathione levels among the groups (p < 0.001), attributed to Group 4 exhibiting higher reduced glutathione levels compared to Groups 1, 2, and 3 (p < 0.001). No significant differences were observed in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.999). Total glutathione levels varied significantly among the groups (p < 0.001), with Group 4 having higher levels than Groups 1, 2, and 3 (p < 0.001). However, there were no significant differences between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in terms of total glutathione levels (p = 0.473, p = 0.747, and p > 0.999, respectively). Regarding oxidized glutathione levels, a significant difference was observed (p < 0.001), with Group 4 showing lower levels than the remaining three groups (p < 0.001). No significant differences were found between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in relation to oxidized glutathione levels (p > 0.999, p = 0.171, and p > 0.999, respectively). Conclusions: The current study revealed that glutathione is a factor influencing the development of new bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the effect of glutathione on the prognosis of bladder cancer.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. Dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

Greenhouse gas (GHG) emission-induced climate change, particularly occurring since the mid-20th century has been considerably affecting short-term weather conditions, such as increasing weather variability, and incidence of extreme weather-related events. Milk production is sensitive to such changes. In this study, we use spatial panel econometric models, Spatial Error Model (SEM) and Spatial Durbin Model (SDM), with a panel dataset at the state-level varying over seasons, to estimate the relationship between weather indicators and milk productivity, in an effort to reduce the bias of omitted climatic variables that can be time-varying and spatially correlated and cannot be directly captured by conventional panel data models. We find an inverse U-shaped effect of summer heat stress on milk production per cow (MPC), indicating that milk production reacts positively to a low-level increase in summer heat stress, and then MPC declines as heat stress continues increasing beyond a threshold value of 72. Additionally, fall precipitation exhibits an inverse U-shaped effect on MPC, showing that milk yield increases at a decreasing rate until fall precipitation rises to 14 inches and then over that threshold milk yield declines at an increasing rate. We also find that, relative to conventional panel data models, spatial panel econometric models could improve prediction performance by leading to smaller in-sample and out-sample root mean squared errors. Our study contributes to the literature by exploring the feasibility of promising spatial panel models and resulting in estimating weather influences on milk productivity with high model predicting performance.

Exploring the growth and physiological response mechanisms of rice under continuous drought stress circumstances can provide a significant scientific foundation and technological assistance for meeting drought difficulties, improving drought resistance and rice (Oryza sativa L.) output, and ensuring food security. In this study, a rice field experiment was conducted under a rain shelter with five different treatments set up: P1 (drought stress from tillering stage), P2 (drought stress from jointing-booting stage), P3 (drought stress from heading-flowering stage), P4 (drought stress from grain filling stage), and CK (adequate water management throughout the growth stage). Continuous drought stress from different growth stages with four levels (mild, medium, serious, and extreme). The results showed that the effects of different drought stress treatments on rice growth varied significantly. Compared with the CK treatment, plant height was reduced by 12.10%, 8.14%, 3.83%, and 1.06% in the P1, P2, P3, and P4 treatments, respectively; and the number of tillers was reduced by 23.83%, 18.91%, 13.47%, and 8.68%, respectively. With the increase in drought stress levels, SPAD values and Rubisco activity of rice leaf continued to decrease; SOD activity showed a decreasing trend, but the decreasing trend of POD and CAT activities was not significant, while MDA content showed an increasing trend. For yield components, continuous drought stress significantly reduced spike length, effective number of spikes, thousand grain weight, grain number per spike, and fruiting rate of rice compared to CK treatments during the growth period. In general, continuous drought stress during the early growth period affected the effective spike number and the grain number per spike. Continuous drought stress after the grain filling stage had the least effect on yield and water use efficiency was much higher than other treatments. The results of these studies reveal the response of rice growth and physiology to continuous drought stress, which is important for agricultural practices.

SerpinB3, a member of the serine-protease inhibitor family, has emerged as a crucial player in various physiological and pathological processes. Initially identified as an oncogenic factor in squamous cell carcinomas, SerpinB3's intricate involvement extends from fibrosis progression and cancer to cell protection in acute oxidative stress conditions. This review explores the multi-faceted roles of SerpinB3, focusing on its implications in fibrosis, metabolic syndrome, carcino-genesis, and immune system impairment. Furthermore, its involvement in tissue protection from oxidative stress and wound healing underscores its potential as diagnostic and therapeutic tool. Recent studies have described the therapeutic potential of targeting SerpinB3 through its upstream regulators, offering novel strategies for cancer treatment development. Overall, this review underscores the importance of further research to fully elucidate the mechanisms of ac-tion of SerpinB3 and to exploit its therapeutic potential across various medical conditions.

The motor protein Prestin found in the outer hair cells (OHCs) of the inner ear is responsible for producing high sensitivity and sharp frequency selectivity for mammalian hearing. Some studies have suggested that Prestin could serve as a serological biomarker for cochlear damage since OHCs are highly vulnerable to damage from various sources of insults. However, the reported data are inconsistent and lack appropriate negative controls. To investigate this further, we measured Prestin quantities in the bloodstream using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that kill OHCs rapidly. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect Prestin specifically. The ELISA kit that could detect Prestin protein from cochlear homogenates failed to detect Prestin in the bloodstream despite significant damage to OHCs in cochleae. Furthermore, the optical densities of samples, which correlate to Prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice.

Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.

In recent years, the chiral biological effects of nanomedicines have become a subject of widespread interest. The research focus has been on understanding the influence of material chirality on cellular transcription and metabolism. Stress granules are membraneless organelles formed through liquid-liquid phase separation of G3BP1 proteins and related compartments. They have been extensively studied and proven to be closely associated with cellular damage repair and metabolism. However, the role and mechanism of chiral nanomaterials in modulating stress granules remain unknown. The aim of this study was to investigate the expression and structural characteristics of stress granules under the individual influence of chiral nanomaterials and in combination with chemotherapy. To achieve this, we constructed a library of chiral ligand-modified materials and employed immunofluorescence, live-cell imaging, and fluorescence recovery after photobleaching assays. We also used proximity labeling techniques combined with proteomics analysis to identify the protein corona adsorbed on the surface of the nanomaterials and explore their relationship with nanomaterial chirality. Our results demonstrate that the assembly of stress granules is chiral-dependent and can be regulated by chiral nanomaterials. Furthermore, we achieved enhanced chemotherapy sensitivity in cancer cells and protected normal cells by exploiting the chiral-dependent modulation of material assembly in stress granules. This study provides important insights into the regulation of membraneless cellular structures based on chiral biological effects.

Nowadays, the identification and characterization of grapevine cultivars resilient to climate and water stress while preserving quality traits is crucial for the wine industry. Therefore, the objective of this work was to characterize according to their aromatic potential 9 white and 6 red minority cultivars recently recovered from Castilla-La Mancha region (Spain), subjected at two different water deficit regimes: rainfed, with subsistence irrigation, and irrigated. For this, the varietal aromatic potential index (IPAv) and the detailed aromatic composition were analyzed by HS-SBSE-GC/MS, in extracts of two different ph. For IPAv values, red varieties did not show a clear trend with respect to irrigation. However, in white minority varieties, higher values were obtained under irrigation conditions. Thus, a clear differentiation of the minority varieties in comparison to the references was observed, primarily attributed to the content of esters and acids, in both white and red varieties. A notable contrast was observed at different pH, indicating a greater extractability of certain compounds like linalool, under more acidic conditions. This suggests that some recovered minority cultivars could be promising for cultivation in semi-arid regions with limited water, contributing to the wine sector sustainability in the future.

Inhaled particulate matter (PM) is a key player in the millions of yearly deaths worldwide related to air pollution. The oxidative potential of PM provides an indication of its ability to promote an oxidative environment. When the human lungs are exposed to PM, the reactive oxygen species (ROS) generated in such oxidative environment, if excessive, may lead to cell damage via oxidative stress. Inflammation, endoplasmic reticulum stress, airway remodeling, and many different cell death modes (apoptosis, ferroptosis, pyroptosis, among others) can be triggered by oxidative stress via complex molecular pathways, which also involve the adaptive cellular response. But ROS can also directly interact with macromolecules such as proteins and lipids, as well as nucleic acids, having been reported to induce DNA damage and epigenetic modifications, which jeopardizes homeostasis. These facts have been extensively studied in in vitro models and confirmed in in vivo models.In this review, we delve beyond conventional assessments of airborne particles, discussing their oxidative potential and the PM-induced ROS-mediated cellular damage observed in in vitro models. The close link between oxidative stress and inflammation, and the manifestation of different cell death modes is highlighted by reviewing the latest literature. The effects of ROS on the balance of DNA damage and repair, carcinogenicity and epigenetics interplay are then analyzed. Finally, we expand on the latest reports on the antioxidants’ potential to counteract the deleterious effects of ROS, and disclose future perspectives for the topic.

Introduction the outbreak of the Israel-Gaza conflict, initiated by a major attack on the civilian population in Israel provided a tragic opportunity to study the community wide association between severe emotional stressors related to acts of war and the incidence and clinical characteristics of Takotsubo cardiomyopathy (TCM) in this scenario. Methods Eight consecutive cases of TCM diagnosed during the first 50 days of the Israel-Gaza conflict were retrospectively collected from two southern medical centers who provided care to most of the war victims throughout the period of monitoring. The medical records were thoroughly reviewed and analyzed. Results During the monitoring period, the incidence of TCM increased substantially compared to the control period. Eight patients were included in the analysis. All patients were female and 100% of patients presented within the first 3 weeks of conflict whereas after this initial phase, despite the continuing war, the incidence of TCM reverted to pre-conflict levels. Two patients (25%) were under 50 years of age. All patients had hazardous clinical characteristics including severe left ventricular (LV) dysfunction (≤35%) and prolonged QTc interval (>500 ms). Five patients (62.5%) experienced complications. Nevertheless, no in-hospital mortality was reported. Conclusions Repeated exposure to severe emotional stress, on both personal and national level, due to mass crisis such as war is associated with an increased incidence of TCM potentially with high-risk phenotype in comparison to TCM following other, less potent, psychological insults.

The study aimed to determine the effect of heat stress (HS) on reproductive parameters [calving to first service (CTFS) and first service conception rate (FSCR)] and general physiological responses [rectal temperature (RT) and respiratory rate (RR)] in tropical Holstein Friesian dairy cows raised in Ratchaburi province, Thailand. Cows were divided into a moderate HS (n = 22) and a mild HS (n = 22) group. Cycling cows were detected and injected with PGF2α at the beginning of the experimental period. Reproductive and physiological parameters were recorded. The average temperature humidity indices experienced by the cows were 80.67 ± 0.79 and 77.81 ± 1.09 for the moderate and mild HS groups, respectively. Cows showed significantly lower RT and RR in the mild (38.47 ± 0.21°C and 41.04 ± 4.55 bpm, respectively) than in the moderate HS group (38.87 ± 0.15°C and 51.17 ± 10.52 bpm). Under mild HS, cows showed a better response to injection of PGF2α than those under moderate HS. The percentage of cows that ovulated after being induced by PGF2α and showed estrus signs was higher in the mild than the moderate HS groups (54.55% versus 18.18%). Furthermore, the FSCR of cows under mild HS tended to be higher than in the moderate HS group (54.55 % and 42.11%, respectively), while the average CTFS interval was significantly shorter under mild than moderate HS (69.47 ± 18.18 and 84.60 ± 27.68, respectively). These results indicate that HS impairs reproductive performance in cross-bred Holstein cows, especially in moderate HS conditions.

This paper presents geometric analyses of welded frames after free relaxing and vibratory stress relief (VSR). Respected frames were tested components of a prototype packaging machine. Two types of relaxation were carried out to remove stresses introduced as a result of welding process. One of the frame was subjected to free relaxing, while the other one to accelerated vibration relaxing. Detection of the frame geometry changes was performed using a photogrammetric system. In addition, an evaluation of the geometry change was conducted for fifteen variants of steel frame support. A comparative analysis of the geometric deviations of the frames after free and vibratory stress relief confirmed the assumption that the frame after vibration stress relief better reproduces the nominal dimensions. Nevertheless, it should be emphasized that after vibratory stress relief the frame is not subject to further deformation, which is a desirable effect. In the case of free relaxing, the frame undergoes dimensional changes in a random manner. In summary, carrying out accelerated vibratory stress relief allows control of spontaneous dimensional changes in the designed frame of a packaging machine resulting from spontaneous relaxation of stresses arising from the welding process. The shortening of the relaxation process of the welded frame is also an unquestionable advantage.

Accurate measurement of systemic financial risk is critical to maintaining the stability of financial markets. Taking China as the subject of investigation, the Chinese Financial Stress Index (CFSI) indicator system was con-structed by integrating six dimensions and employing Gray Relation Analysis (GRA) for dimensionality reduction of the indicators. The CFSI was derived using the Attribute Hierarchy Model (AHM) method with the Criteria Importance Through the Intercriteria Correlation (CRITIC) method, and an Improved Gravitational Search Algorithm (IGSA) optimized Radial Basis Function Neural Network (RBFNN) was proposed for out-of-sample prediction of CFSI trends from 2024 to 2026. By analyzing the trend of financial pressure indicators, the relationship between financial pressure and economic activity can be effectively identified. The research findings indicate that: (1) The CFSI is capable of accurately reflecting the current financial stress situation in China; (2) The IGSA-RBFNN demonstrates good robustness and generalization capabilities, predicting that the CFSI index will reach a peak value of 0.543 by the end of 2024, and there exists a regular pattern of stress rebound towards the end of each year. The novel methodology benefits policymakers and regulatory authorities to formulate preventive measures and risk management by identifying potential risks and vulnerabilities in advance.