Materials characterised by magnetorheological properties are non-classic engineering materials. A significant increase in the interest of scientific community in materials from this group can be observed over the recent several years. The results of research presented in this article are oriented on the examination of said materials’ mechanical properties. In order to do so, stress relaxation tests were conducted on cylindrical samples of magnetorheological elastomers loaded with compressive stress for various values of magnetic induction (B1 = 0 mT, B2 = 32 mT, B3 = 48 mT, and B4 = 64 mT) and temperature (T1 = 25° C, T2 = 30° C, and T3 = 40° C). The results of these tests indicate that the stiffness of examined samples increases along with the increase of magnetic field induction and decreases along with the increase of temperature. On this basis, it has been determined that: the biggest stress amplitude change caused by the influence of magnetic field was σ0ΔB = 12.7% and the biggest stress amplitude change caused by the influence of temperature was σ0ΔT = 11.3%. As a result of applying a mathematical model, it has been indicated that the stress relaxation in the examined magnetorheological elastomer for the adopted time range (t = 3600 s) has a hyperbolic decline nature. The collected test results point to examined materials being characterised by extensive rheological properties, which leads to a conclusion that it is necessary to conduct further tests in this scope.

On March 2020 strict measures took place in Finland to limit the COVID -19 pandemic. A majority of the Finnish COVID -19 –patients have been located in the southern Finland and consequently cared for in the HUS Helsinki University Hospital. During the ongoing pandemic, HUS personnel’s psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. The baseline survey in June 2020 was sent to 25494 HUS employees out of whom 4804 (19%) answered; altogether 62.4% of the respondents were nursing staff and 8.9% medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from the baseline survey. Out of those who were directly involved in pandemic patients` care, 43.4% reported potentially traumatic COVID-19 pandemic-related experiences vs. 21.8% among the other (p < 0.001). While over a half of the personnel was symptomless, a group of respondents reported pandemic work –related traumatic events and concurrent depressive, insomnia and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel and PTEs were present especially among nursing staff.

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield a 4-PBA-glutamic acid conjugate (PBA-GA) and a 4-PBA-aspartic acid conjugate (PBA-AA). The PBA derivatives were converted to 4-PBA in the cecal contents, where the conversion was greater with PBA-GA. After oral administration of PBA-GA (oral PBA-GA), millimolar levels of PBA were accumulated in the cecum, whereas 4-PBA was not detected in the blood, indicating the targeting of PBA-GA to the large intestine. At concentrations in the cecum achievable by oral PBA-GA, 4-PBA effectively attenuated ER stress in human colon epithelial cells. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon. Moreover, oral PBA-GA substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably through the attenuation of ER stress in the inflamed colon.

Nonhost disease resistance is the most common type of plant defense mechanism against potential pathogens. In this study, the metabolic enzyme formate dehydrogenase (FDH1) was identified to be involved in nonhost disease resistance in Nicotiana benthamiana and Arabidopsis thaliana. In Arabidopsis, AtFDH1 was highly upregulated in response to both host and nonhost bacterial pathogens. Arabidopsis Atfdh1 mutants were compromised in nonhost resistance, basal resistance, and gene-for-gene resistance. The expression patterns of salicylic acid (SA) and jasmonic acid (JA) marker genes after pathogen infections in Atfdh1 mutant indicated that SA is most likely involved in the FDH1-mediated plant defense response to both host and nonhost bacterial pathogens. Previous studies reported that FDH1 localizes to only mitochondria, or both mitochondria and chloroplasts. Our results showed that the AtFDH1 localized to mitochondria and the amount of FDH1 localized to mitochondria increased upon infection with host or nonhost pathogens. Interestingly, the subcellular localization of FDH1 was observed in both mitochondria and chloroplasts after infection with a nonhost pathogen in Arabidopsis. We speculate that FDH1 plays a role in cellular signaling networks between mitochondria and chloroplasts to produce coordinated defense responses such as SA-induced reactive oxygen species (ROS) generation and hypersensitive response (HR)-induced cell death against nonhost bacterial pathogens.

A human organism depends on stable glucose blood levels in order to maintain the metabolic needs. Glucose is considered as the most important energy source and glycolysis is postulated as a backbone pathway. However, when glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. PPP generates and maintains levels of NADPH needed for reduction of oxidized glutathione and protein thiols, synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. Flux of glucose into a PPP, particularly under extreme oxidative and toxic challenges is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP⁺ that is required for activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload and provides new insights into positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system. Since incomplete UPR could lead to unresolved and persistent ER stress, we found that ZIKV infection was associated with an abnormal accumulation of viral envelope proteins, which were aggregated with non-native disulfide bridges. As the presence of these “amyloid like” protein polymers may be cytopathic, our observations provide new insights into specific neuropathologies associated with ZIKA virus infections.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

The aim of work is to derive an explicit expression for a function of vertical mixing induced by wind-waves. To this end, in the Navier-Stokes equations, a current is decomposed into four constituents: the mean flow, the wave-orbital motion, the wave-induced turbulent and the background turbulent currents. This decomposition allows separating the wave-induced Reynolds stress, Rw, from the background one, Rb. To make a statistical closure for Rw, the Prandtl approach for the background turbulent fluctuations is used that results in an implicit expression for the wave-induced vertical mixing function, Bv. Expression for Bv is specified based on the author’s results for the eddy viscosity found earlier in the frame of the three-layer concept for a wavy air–sea interface, used for modelling wind-drift currents [1]. Finally, the explicit parameterization for Bv(a, u*, z) is found as a linear function in both the wave amplitude at depth z, a(z), and the friction velocity in the air, u*. The linear dependence of function Bv(a) on the wave amplitude provides the enhanced vertical mixing induced by wind–waves in comparison with function Bv(a) having the cubic dependence found in [2], as far as the wind-wave amplitude a(z) decays exponentially with depth.

Flying-fox populations are increasingly threatened by heat events, starvation events and other stressors due to habitat clearing and human/flying-fox conflict.These factors are unlikely to resolve, meaning that a well-coordinated and timely approach to flying-fox disasters is imperative for the mitigation of further flying-fox population impacts.

Oxidative stress negatively affects folliculogenesis and embryo development. However, a reliable and biologically accurate indicator of oxidative stress does not yet exist. On these bases, the aim of this study was to assess -and compare- blood and follicular fluid (FF) redox status in 45 infertile subjects (and 45 age-matched controls) undergoing in vitro fertilization (IVF) and to establish its connection with the outcome of IVF. Blood and FF were obtained at the time of egg retrieval and immediately analyzed. Firstly, ROS production in blood leukocytes and in granulosa cells was assessed. Oxidative stress markers in blood and in granulosa cells resulted significantly (p<0.001) increased in infertile patients compared to controls. Then, a redox index was obtained in plasma and in FF of patients and controls. The main findings emerging from our study in infertile women are: i) blood oxidative stress reflects FF oxidative stress as demonstrated by the significant correlation between blood redox markers and FF redox markers; ii) a significant correlation between oxidative stress parameters and the considered IVF outcomes is present. We suggest the strict monitoring of the redox parameters for the improvement of assisted reproductive techniques success rate and infertility management.

Attention deficit hyperactivity disorder (ADHD) results in various functioning impairments in children’s lives and families. Parents of children with ADHD report high levels of parenting stress, low levels of parental self-efficacy and use of more authoritarian and/or permissive parenting practices than parents of typically developing children. Intervention programs need to address both children’s and parents’ needs and multimodal intervention programs could cover this demand. The aim of this study was to examine the efficacy of “Child ViReal Support Program” - a multi-level evidence-based comprehensive program - on parenting stress, parental self-efficacy, parenting practices, and the core symptoms of children’s ADHD. Families with a child diagnosed with ADHD (n = 16) were randomly allocated to two groups (PC and CP; P = parent training, C = child training) and a cross-over design was utilized. Participating parents completed, in four different times during the study, the Parenting Stress Index-Short Form, the Parenting Sense of Competence Scale, the Parenting Styles and Dimensions Questionnaire-Short Version and the parent form of the ADHD Rating Scale-IV. Parents from both groups, after their participation in the parent training, demonstrated reduced parenting stress, enhanced parental self-efficacy and increased the employ of democratic parenting practices. More than that, they reported decreased levels of inattention and impulsivity/hyperactivity for their children. Evidence-based multi-level intervention programs could produce positive effects in parents and children by incorporating effective methods and tools in accordance with the needs and the demands of the family context.

The production of nanoparticles has recently surged due to their varied applications in biomedical, pharmaceutical, textile, and electronic sectors. However, this rapid increase in nanoparticle manufacturing has raised concerns about environmental pollution, particularly due to their potential adverse effects on human health. Among the various concerns, inhalation exposure to nanoparticles poses significant risks, especially affecting the respiratory system. Airway epithelial cells play a crucial role as the primary defense against inhaled particulate matter and pathogens. Studies have shown that nanoparticles can disrupt the airway epithelial barrier, triggering inflammatory responses, generating reactive oxygen species, and compromising cell viability. However, our understanding of how different types of nanoparticles specifically impact the airway epithelial barrier remains limited. To investigate nanoparticle-induced cellular responses and barrier dysfunction, both in vitro cell culture models and in vivo murine models are commonly utilized. In this review, we discuss the methodologies frequently employed to assess nanoparticle toxicity and barrier disruption. Furthermore, we analyze and compare the distinct effects of various nanoparticle types on the airway epithelial barrier. By elucidating the diverse responses elicited by different nanoparticles, we aim to provide insights that can guide future research endeavors in assessing and mitigating the potential risks associated with nanoparticle exposure.

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable wireless monitoring and interaction with functional activity of microorganisms. Of high relevance is the membrane potential as it is one of the most important parameters of living cells. In particular, the complex mechanisms of the cell’s membrane potential are comparable to the dynamics of bacteria membranes, providing a simplified platform for advancing the current techniques and knowledge of general bio-particle dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of bacteria on a microfluidic-based framework for sensing the membrane potential of bacteria. The results enable to further advance the state-of-the-art of electromagnetic bacteria sensing and microfluidic control, and their implication for measuring and interacting with the cell and its membrane potentials, which is of great importance for developing new biotechnological engineered systems and solutions.

Ascorbate; Pars Plana Vitrectomy; Open Angle Glaucoma; Oxidative Stress; Vitreous Me-tabolism 0. How to Use This Template

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

LSU (RESPONSE TO LOW SULFUR) proteins belong to a plant-specific gene family initially characterized by their strong induction in response to sulfate (S) deficiency. However, little is known about the LSU gene repertoire and evolution of this family in land plants. In this work, a total of 270 LSU family members were identified using 134 land plant species with whole genome sequence available. Phylogenetic analysis revealed that LSU genes belong to a Spermatophyta-specific gene family, and their homologs are distributed in three major groups, two for dicotyledons and one group for monocotyledons. Moreover, we analyzed the expression of LSU genes in one representative species of each phylogenetic group (wheat, tomato and Arabidopsis) and found a conserved response to S-deficiency, suggesting that these genes might play a key role in S stress responses. Accordingly, Arabidopsis lsu2 knockout mutant plants showed increased levels of internal sulfate content and lower levels of expression of different key genes involved in S deficiency and metabolism like SDI2 and APR3. In summary, our results indicate that LSU genes are evolutionarily conserved in angiosperms and that specific members of this family might play an important role regulation of S transport and assimilation.

This initial report of a longitudinal study of 192 English hospital nurses has measured Nursing Values (the 6Cs of nursing); Personality, Self-Esteem and Depression; Burnout Potential; Work-Life Balance Stress; ‘Hardy Personality’; and Intention to Leave Nursing. Correlational, component and cluster analysis identifies four groups: “The Soldiers” (N = 79) , with medium scores on most measures, who bravely ‘soldier on’ in their nursing roles, in the face of numerous financial cuts to the National Health Service, and worsening nurse-patient ratios; “Cheerful Professionals” (N = 54), coping successfully with nursing roles, and a variety of challenges, in upwardly mobile careers; “High Achievers” (N = 39), senior nurses with strong profiles of a ‘hardy personality’, and commitment to fundamental nursing values; “Highly Stressed, Potential Leavers” (N = 20), with indicators of significant psychological distress, and difficulty in coping with nursing role challenges. We propose a model of co-counselling and social support for this distressed group, by nurses who are coping more successfully with multiple challenges. We discuss the role of nurse educators in fostering nursing values, and developing and supporting ‘hardy personality’ and emotional resilience in recruits to nursing. This study is framed within the disciplinary approach of Critical Realism, which identifies the value basis for research and dialogue in developing strategies for social change.

Salinity is considered as one of the most important abiotic challenges that affect crop productivity. Plant hormones, including salicylic acid (SA), are key factors in the defence signalling output triggered during plant responses against environmental stresses. We have previously reported in peach a new SA biosynthetic pathway from mandelonitrile (MD), the molecule at the hub of the cyanogenic glucoside turnover in Prunus sp. In this work, we have studied whether this new SA biosynthetic pathway is also present in plum and the possible role this pathway plays in plant plasticity under salinity, focusing on the transgenic plum line J8-1, which displays stress tolerance via an enhanced antioxidant capacity. The SA biosynthesis from MD in non-transgenic and J8-1 micropropagated plum shoots was studied by metabolomics. Then the response of J8-1 to salt stress in presence of MD or Phe (MD precursor) was assayed by measuring: chlorophyll content and fluorescence parameters, stress related hormones, levels of non-enzymatic antioxidants, the expression of two genes coding redox-related proteins, and the content of soluble nutrients. The results from in vitro assays suggest that the SA synthesis from the MD pathway demonstrated in peach is not clearly present in plum, at least under in vitro conditions. Nevertheless, in J8-1 NaCl-stressed seedlings, an increase in SA was recorded as a result of the MD treatment, suggesting that MD could be involved in the SA biosynthesis under NaCl stress conditions in plum plants. We have also shown that the plum line J8-1 was tolerant to NaCl under greenhouse conditions, and this response was somewhat different in MD-treated plants. In that regards, the MD treatment produced an increase in SA, jasmonic acid (JA) and reduced ascorbate (ASC) contents as well as in the coefficient of non-photochemical quenching (qN) and the gene expression of Non-Expressor of Pathogenesis-Related 1 (NPR1) and thioredoxin H (TrxH) under salinity conditions, suggesting a crosstalk between different signalling pathways (NPR1/Trx and SA/JA) leading to salinity tolerance in the transgenic plum line J8-1.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

This study comprehensively investigates the stress distribution and aging effects in Ethylene Propylene Diene Monomer (EPDM) and Liquid Silicone Rubber (LSR) gasket materials through a novel integration of hyperelastic modeling and advanced machine learning techniques. By employing the Mooney-Rivlin, Ogden, and Yeoh hyperelastic models, we evaluate the mechanical behavior of EPDM and LSR under conditions of no aging, heat aging, and combined heat and sulfuric acid exposure. Each model reveals distinct sensitivities to stress distribution and material deformation, providing unique insights into material degradation processes. Additionally, we utilize machine learning for predictive analysis, enhancing our understanding of stress responses and identifying critical aging effects. The findings offer practical implications for selecting suitable gasket materials and developing predictive maintenance strategies in industrial applications, such as fuel cells, where material integrity under stress and aging is paramount. This dual approach highlights the mechanical resilience and vulnerabilities of EPDM and LSR and opens avenues for real-time predictive analytics and material performance optimization.

Increased salinity caused by saltwater intrusion or runoff from de-icing salts can severely affect freshwater vegetation and deteriorate aquatic ecosystems. These habitats can be restored with freshwater ecotypes (locally adapted populations) that tolerate above-normal salinity. Vallisneria americana is a prominent species in many freshwater ecosystems that responds differently to abiotic conditions such as substrate composition and fertility, so in this study we evaluated the effects of salt stress on 24 ecotypes of V. americana. Instant Ocean aquarium salt was used to create saline solutions [0.2 to 20.0 parts per thousand (ppt)], then plants were abruptly exposed to these solutions and maintained in these concentrations for 5 weeks before being visually assessed for quality and destructively harvested. Analysis of variance and non-linear regression were used to calculate LC₅₀ values – the lethal concentration of salt that reduced plant biomass and quality by 50% compared to control treatment. Growth rate and visual quality varied significantly among ecotypes, and ecotypes that were most and least sensitive to salt had 50% biomass reductions at 0.47 and 9.10 ppt, respectively. All ecotypes survived 10.0 ppt salinity concentration but none survived at 20.0 ppt, which suggests the maximum salinity concentration tolerated by these ecotypes is between 15.0 and 20.0 ppt.

This study determines the equivalent stress intensity factor (SIF) model that best fits the experimental behavior of low-carbon steel under mixed mode (I and II). The study assessed Tanaka, Richard, and Pook's equivalent SIF models. The theoretical values used for comparison correspond to experimental results in a modified C(T) geometry by machining a hole ahead of the crack tip subjected to fatigue loads with a load ratio of R = 0.1. The comparison involved the SIF for six experimental points and the values computed through the numerical simulation. The Paris, Klesnil, and modified Forman-Newman crack growth models were used with each equivalent SIF to analyze the prediction in the estimated number of cycles. The Klesnil model showed the closest prediction since the error between the calculated and experimentally recorded number of cycles is the lowest. However, the material behavior reflects a reduced crack propagation rate attributed to plasticity in the crack tip. Results suggest that Asaro equivalent SIF conservatively estimates the element lifespan with increasing errors from 2.3% at the start of growth to 27 % at the end of the calculation.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

Egypt faces numerous challenges in achieving food and nutritional security, due largely to its unique geography, water stress, and population growth. However, nontraditional crops and pseudo cereals such as buckwheat, quinoa, sorghum, teff, and millet offer promising avenues for sustainable agricultural development and improved nutrition. These crops exhibit high tolerance to adverse environmental conditions such as soil salinity and drought and are rich in essential nutrients like protein, amino acids, and vitamins. They also present an economic advantage due to their short growing seasons and adaptability to marginal lands. Recent advancements in remote sensing and Geographic Information Systems (GIS) technology, along with crop simulation models, provide further opportunities for optimizing land and water resources for these nontraditional crops. Their exceptional nutritional values, including low glycemic indices and gluten-free properties, make them well-suited to address current health challenges, such as malnutrition and the increasing prevalence of non-communicable diseases. The study emphasizes the need for further research to investigate land suitability, water management, and economic viability for the cultivation and commercialization of these crops. By leveraging these opportunities, Egypt has the potential to not only close its food gap but also improve overall nutritional well-being, contributing to both food security and sustainable agriculture.

Radical changes in the idea of the organization of the intracellular space that occurred in the early 2010-s made it possible to consider the formation and functioning of the so-called membrane-less organelles (MLOs) based on a single physical principle: the liquid-liquid phase separation (LLPS) of biopolymers. Weak nonspecific inter- and intramolecular interactions of disordered polymers, primarily of intrinsically disordered proteins and RNA, play a central role in the initiation and regulation of these processes. On the other hand, in some cases, the "maturation" of MLOs can be accompanied by the "liquid-gel” phase transition, where other types of interactions can play a significant role in reorganization of their structure. In this work, we conducted a bioinformatics analysis of the propensity of the proteomes of two membrane-less organelles formed in response to stress in the same compartment, nucleolus, for spontaneous phase separation and looked at their intrinsic disorder predispositions. These nucleolar MLOs, amyloid bodies (A-bodies) formed in the response to acidosis and heat shock and nuclear stress bodies (nSBs), are characterized by the partially overlapping composition, but show different functional activities and morphologies. We show that the proteomes of these nucleolar biocondensates are differently enriched in proteins, many of with high potential for spontaneous LLPS that correlates with different morphology and function of these organelles. The results of these analyses allowed us to evaluate the role of weak interactions in the formation and functioning of these important organelles.

Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor with a 5-year survival of <1%. Up to 80% of DIPG tumors contain a specific K27M mutation in one of two genes encoding histone H3 (H3K27M). Furthermore, p53 mutations found in >70-80% of H3K27M DIPG, and mutant p53 status is associated with a decreased response to radiation treatment and worse overall prognosis. Recent evidence indicates that H3K27M mutation disrupts tri-methylation at H3K27 leading to aberrant gene expression. Jumonji family histone demethylases collaborates with H3K27 mutation in DIPG by erasing H3K27 trimethylation and thus contributing to derepression of genes involved in tumorigenesis. Since the first line treatment for pediatric DIPG is fractionated radiation, we investigated the effects of Jumonji demethylase inhibition with GSK-J4, and mutant p53 targeting/oxidative stress induction with APR-246, on radio-sensitization of human H3K27M DIPG cells. Both APR-246 and GSK-J4 displayed growth inhibitory effects as single agents in H3K27M DIPG cells. Furthermore, both of these agents elicited mild radiosensitizing effects in human DIPG cells (sensitizer enhancement ratios (SERs) of 1.12 and 1.35, respectively; p<0.05). Strikingly, a combination of APR-246 and GSK-J4 displayed a significant enhancement of radiosensitization, with SER of 1.50 (p<0.05) at sub-micro-molar concentrations of the drugs (0.5 μM). The molecular mechanism of the observed radiosensitization appears to involve DNA damage repair deficiency triggered by APR-246/GSK-J4, leading to the induction of apoptotic cell death. Thus, a therapeutic approach of combined targeting of mutant p53, oxidative stress induction, and Jumonji demethylase inhibition with radiation in DIPG warrants further investigation.

1) Background: Climate change may subject forests to climate conditions to which they are not adapted. Elevated temperatures reduce net photosynthesis by increasing respiration rates and increasingly long droughts dramatically increase morbidity. CO₂ enrichment enhances productivity, but it is not clear to what extent CO₂ enrichment can offset the negative effects of elevated temperatures and longer droughts. 2) Methods: We used a mechanistic landscape model to conduct controlled simulation experiments manipulating CO₂ concentration, temperature, drought length and soil water capacity. 3) Results: We found that elevated CO₂ stimulates productivity such that it dwarfs the negative effect caused by elevated temperature. Energy reserves were not as strongly mitigated by elevated CO₂, and mortality of less competitive cohorts increased. Drought length had a surprisingly small effect on productivity measures, but had a marked negative effect on mortality risk. 4) Conclusions: Elevated CO₂ compensated for the negative effect of longer droughts in terms of productivity measures, but not survival measures.

Dementia patients express a set of problematic and deteriorating symptoms, along self-care dependency. Overtime, the mental health of family caregivers of persons with dementia may suffer, putting them at a high risk for psychopathology, which may be associated with endangered wellbeing of demented people. This cross-sectional study examined the psychometric properties of the Depression Anxiety Stress Scale 8-items (DASS-8), DASS-12, DASS-21 in a convenient sample of 571 caregivers from northern Italy and southern Switzerland (Mean age = 53, SD = 12, range = 24–89 years). A bifactor structure of the three measures had the best fit; some items of the DASS-12/DASS-21 failed to load on their domain-specific factors. The three-factor structure was invariant across various groups (e.g., gender, education, etc.), expressed adequate reliability and convergent validity, and had strong positive correlation with the 3-item UCLA Loneliness Scale (UCLALS3). Dementia type had no effect on distress scores, which were higher among females, adult children caregivers, those caring for dependent patients, and those who received help with care. For 54.9 and 38.8% of the latter, care was provided by relatives and health professionals, respectively. Since the DASS-8 expresses adequate psychometrics comparable with the DASS-21, it may be used as a brief measure of distress in this population.

Acute kidney injury (AKI), especially if recurring represents a risk factor for future chronic kidney disease. In intensive care units, increased intraabdominal pressure is well-recognized as a significant contributor of AKI. However, the importance of transiently increased intra-abdominal pressures procedures is less commonly appreciated during laparoscopic surgery, the use of which has rapidly increased over the last few decades. Unlike the well-known autoregulation of the renal cortical circulation, medulla perfusion is modulated via partially independent regulatory mechanisms and strongly impacted by changes in venous and lymphatic pressures. In our review paper, we will provide a comprehensive overview of this evolving topic, covering a broad range from basic pathophysiology up to and including current clinical relevance. Key regulators of oxidative stress such as ischemia-reperfusion injury, the activation of inflammatory response and humoral changes interacting with procedural pneumoperitoneum formation and AKI risk will be recounted. Moreover, we present an in-depth review of the interaction of pneumoperitoneum formation with general anesthetic agents and animal models of congestive heart failure. A better understanding of the relationship between pneumoperitoneum formation and renal perfusion will support basic and clinical research, leading to improved clinical care and collaboration among specialists.

At the beginning of the 21st century, it became obvious that radical changes had taken place in the concept of living matter and, in particular, in the concept of the organization of intracellular space. The accumulated data testify to the essential importance of phase transitions of biopolymers (first of all, intrinsically disordered proteins and RNA) in the spatiotemporal organization of the intracellular space. Of particular interest is the stress-induced reorganization of the intracellular space. Examples of organelles formed in response to stress are nuclear A-bodies and nuclear stress granules. The formation of these organelles is based on LLPS of intrinsically disordered proteins and non-coding RNA. Despite the overlapping composition and similar mechanism of formation, these organelles have different functional activities and physical properties. In this review, we will focus our attention on these MLOs and describe their functions, structure, and mechanism of formation.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and cochlear hypothalamic–pituitary–adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins, and Ca2+-linked transporters and voltage-gated channels. These findings suggest that pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss

Bacteria develop various defense mechanisms against stresses, including the bacteriophage infection. The giant phiKZ phage infection induced the appearance of a pseudo-nucleus inside the bacterial cytoplasm. Here, we used FISH, electron tomography and analytical electron microscopy to study the morphology of this unique nucleus-like shell and to demonstrate the distribution of phiKZ and bacterial DNA in infected P. aeruginosa cells. The maturation of the pseudo-nucleus was traced in short intervals for 40 min after infection. This study was accompanied by the identification of phiKZ and bacterial DNA by real-time RCR. We demonstrated that phage DNA that isolated from the cytoplasm during all infection stages were compacted within the pseudo-nucleus in a specific structure. Bacterial DNA was diminished in the course of infection, but did not completely degrade until at least 40 min after phage application. The content of the total phage DNA, on the other hand, increased. EDX analysis confirmed these results and revealed that, during the infection, Sulfur content in the bacterial cytoplasm increased, which suggests the increase of DNA-binding Met-reach proteins synthesis, which could protect bacterial DNA from stress.

How can neuroscience help everyone to live and care for our confined brains? Understanding and studying human behaviour allows us to measure the impact of such confinement on each of us and to identify those who need help. The challenges are to understand the psychological repercussions following confinement and to understand how neuroscience and neurotechnology can be very interesting tools for dealing with the health crisis. Neuroscience is changing our traditional philosophical and ethical views by providing information about the biological basis of our moral behaviour. The exception of the brain is at the heart of neuroethical thinking and discourse. Neuroethics is an interdisciplinary discipline placed at the intersection between the human sciences and the neurosciences, and aims to help understand how knowledge and research in neurosciences and neurotechnologies will affect the future of society, their impact on humans, relationships, daily life, the labour market ... but also how they can help and provide solutions and answers to the questions of citizens in a health crisis. But it's a double-edged sword, collecting and analyzing brain data in real time seems to be increasingly simple and within everyone's reach, without having the hindsight of the real meaning of these data, allowing one day to read people's thoughts, control them and manipulate them. It is becoming clear that the boundaries between medical and non-medical uses of neuroscience and neurotechnology are becoming very porous, inviting us to reflect on neuroethical issues in order to put safeguards on these uses.

Thermal stresses belong to the leading factors that influence low-temperature cracking behavior of asphalt pavements. During winter, when temperature drops to significantly low values, tensile thermal stresses develop as a result of pavement contraction. Creep test methods can be suitable for the assessment of low-temperature properties of asphalt mixtures. To evaluate the influence of creep test methods on the obtained low-temperature properties of asphalt mixtures, three point bending and uniaxial tensile creep tests were applied and the master curves of stiffness modulus were analyzed. On the basis of creep test results, rheological parameters describing elastic and viscous properties of the asphalt mixtures were determined. Thermal stresses were calculated and compared to tensile strength of the material to obtain the failure temperature of the analyzed asphalt mixtures. It was noted that lower strain values of creep curves were obtained for the Tensile Creep Test (TCT) than for the Bending Beam Creep Test (BBCT), especially at lower temperatures. Results of thermal stress calculations indicated that higher reliability was obtained for the viscoelastic Monismith method based on the TCT results than for the simple quasi-elastic solution of Hills and Brien. The highest agreement with the TSRST results was also obtained for the Monismith method based on the TCT results. No clear relationships were noted between the predicted failure temperature and different methods of thermal stress calculations.

This study investigates the impact of water stress on grapevines, specifically examining the role of rootstocks and aquaporins. Two experiments on potted plants were conducted in central Chile during the summer, under conditions of high water demand, involving various rootstock genotypes and combinations of Cabernet Sauvignon (CS) grafted onto rootstocks. Significant differences were observed among plants in terms of stem water potential, stomatal conductance, and growth rate. Notably, the CS/CS combination consistently displayed the slowest growth rate, regardless of the irrigation treatment. The study also analyzed the expression levels of plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) aquaporins in the leaves of grafted plants. Specifically, VvPIP2;2 aquaporins showed reduced expression after 14 days without irrigation, whereas VvTIP1;1 and VvTIP2;1 expression levels correlated positively with gs responses in grafted plants, suggesting their role in modulating water content in leaves under water stress. TIP aquaporins likely play a significant role in the differential responses of CS plants towards nearly isohydric or anisohydric behaviour. The CS/CS combination exhibited near isohydric behavior, correlating with lower TIP aquaporin expression, while the combination of CS onto 1103P and 101-14 showed higher expression, indicating anisohydric behavior. The findings suggest that grafted plants are more resilient to water stress, supporting the idea that rootstocks can mitigate the effects of water stress on the scion.

The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents and 75 with a single incision sling. The ICIQ-UI-SF, PISQ-12, FSFI, FSDS, and PGI-I were used to assess efficiency and quality of life. In the 29-month follow-up, the bulking agents showed significantly increased efficacy and safety. Compared to the ones treated with a single-incision sling, the patients treated with bulking agents showed less and mild postoperative complications. Furthermore, at our follow-up there was no discernible difference in terms of effectiveness or quality of life between patients treated with bulking agents and those treated with single-incision slings

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

Climate change is affecting the production of temperate fruit crops. Freeze damage, particularly in spring, has resulted in significant economic losses in peach production in the southeastern United States. Research efforts in peach and other Prunus species have primarily focused on dormancy-related traits associated with bloom time, such as chill and heat requirement, with fruitlet freeze tolerance not equally represented. This study reports fruitlet freeze tolerance in 75 peach and nectarine accessions at six freezing temperatures (0 to -10ºC) using electrolyte leakage method over two seasons (2022-2023). Fruitlet freeze tolerance ranged from -3.94 to -10.22 °C with an estimated damage ranging from 16-48% with the majority of the accessions showing tolerance to cold temperatures in the -4 to -6ºC and 25-35% range. Variability in tolerance was noted across years, including some inconsistencies between tolerance group assignments. Grouping based on the estimated damage showed better stability and some accessions changed their grouping from the extremes to an intermediate tolerance group. Interestingly, nectarine accessions were among most tolerant in both seasons. Broad-sense heritability of 0.52 and 0.85, for freeze tolerance and estimated damage, respectively, suggested genetic control of this trait with a potential for improvement via breeding.

ADHD, one of the most prevalent diseases during childhood, we still do not know its precisely origin, although oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in these patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, and the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results show a treatment-related improvement in the redox profile, with the reduction of advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase of the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These result support by the first time the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

The human gut microbiota (GM) is a complex and dynamic ecosystem that hosts trillions of commensal and potentially pathogenic microorganisms. It is crucial in protecting humans from pathogens and in maintaining immune and metabolic homeostasis. Numerous studies have demonstrated that GM has a significant impact on health and disease, including Alzheimer’s disease (AD). AD is a progressive neurodegenerative disorder characterized by impaired short-term memory and cognitive deficits. Patients with AD have been reported to exhibit abnormalities in GM density and species composition. Oxidative stress (OS) has been implicated in the onset and progression of AD, however, the relationship between OS and gut microbiota in AD onset and progression is not clear. Twendee X®︎ (TwX), an oral supplement consisting of 8 active ingredients, has been shown to prevent dementia in mild cognitive impairment (MCI) in humans and substantially improve cognitive impairment in mouse models of AD. This positive effect is achieved through the potency of the combined antioxidants that regulate OS and therefore similar results cannot be achieved by a single antioxidant ingredient. To examine the impact of long-term OS elevation as seen in AD on the body and GM, we examined GM alterations during the initial OS elevation using a rat 2-week OS loading model, and examined the effects of TwX on OS and GM. Furthermore, using a questionnaire survey and fecal samples, we analyzed the impact of TwX on healthy individuals' gut bacteria and the associated effect on their quality of life (QOL). TwX was found to increase the number of bacteria species and their diversity in GM, as well as butyrate-producing bacteria, which tend to be reduced in AD patients. Additionally, TwX improved defecation condition and QOL. The gut bacteria function as part of the homeostatic function during OS elevation, and prophylactic administration of TwX strengthened this function. The results suggests that the preventative effect of TwX on dementia may involve the GM in addition to the other effects previously demonstrated.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Biosensors are indispensable tools to follow plant’s immunity as its spatiotemporal dimension is key in withstanding the complex plant immune signaling. The diversity of genetically encoded biosensors in plants is expanding, covering new analytes with ever higher sensitivity and robustness, but their assortment is limited in some aspects, such as their use to follow biotic stress response, employing more than one biosensor in the same chassis and their implementation into crops. In this review, we focused on the available biosensors that encompass these aspects. We show that in vivo imaging of calcium and reactive oxygen species is satisfactorily covered with the available genetically encoded biosensors, while on the other hand they are still underrepresented when it comes to imaging of the main three hormonal players of the immune response, salicylic acid, ethylene and jasmonic acid. Following more than one analyte in the same chassis, upon one or more conditions has so far been possible by using the most advanced genetically encoded biosensors in plants which allow to monitor calcium and two main hormonal pathways involved in plant development, auxin and cytokinin. These kinds of biosensors are also the most evolved in crops. In the last section, we gathered the challenges in the use of the biosensors and showed some strategies to overcome them.

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

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

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

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

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

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

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

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

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

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

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

The effect of elastic constants, cij, on the nature (easy or difficult) of a cleavage system in YBa2Cu3O7−δ is investigated, by employing a novel three-dimensional eigenfunction expansion technique, based in part on separation of the thickness-variable and partly a modified Frobenius type series expansion technique in conjunction with the Eshelby-Stroh formalism. Out of the available three complete sets of elastic constants, the first constitutes an estimate, while the second assumes tetragonal symmetry. This leaves only the experimental measurements by resonant ultrasound spectroscopy, despite reported values of c12 and to a lesser extent, c66, being excessively high. The present investigation considers six through-thickness crack systems weakening orthorhombic YBCO mon-crystalline plates. More important, the present approach predicts whether a crack would propagate in its original plane/direction or deflect to a different one. This fracture mechanics criterion is then employed for accurate determination of the full set of elastic constants of mono-crystalline YBCO. Finally, generally unavailable results, pertaining to the through-thickness variations of stress intensity factors and energy release rates for a crack corresponding to symmetric and skew-symmetric hyperbolic cosine loads that also satisfy the boundary conditions on the bounding surfaces of an orthorhombic monocrystalline plate bridge a longstanding gap in the field.

Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.

A consistent factor in the epidemic of chronic disease is a pro-inflammatory metabolic state. The ability of clinicians to use nutrients to balance inflammation by supporting oxidant homeostasis rests on the quality of research within the field of antioxidants. Understanding the intersection of two prominent theories regarding the role of antioxidants in quelling inflammation, nutritional hormesis and oxidant scavenging, will enable the therapeutic use of antioxidants in clinical practice. This review investigates the less well-established theory, nutritional hormesis, which has not been comprehensively reviewed recently to our knowledge. To understand the state of research on the hormetic response, we conducted a comprehensive literature review describing the relationship between dietary antioxidants, hormesis, and chronic disease. We used an adaptive search strategy in PubMed and Scopus, retrieving a total of 343 articles, of which 218 were unique. Title and abstract screenings were conducted by two reviewers independently with a third as a tiebreaker, resulting in 152 articles included in this review. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were conducted in humans. Limitations exist in translating plant/cell/animal models into the complexities of human biochemistry and physiology that warrant consideration before extrapolating such results into clinical practice. A critical hurdle in our literature review process is the lack of standardized nomenclature describing the hormetic effect in the research community that challenges the ability to comprehensively review the subject matter. Further, aA knowledge gap exists between the cell culture and animal model research that shows a biphasic, hormetic quality to the role of antioxidants and the observational human studies, which have yet to corroborate these findings. Therefore, we cannot accurately translate this research into clinical care at this time.

Climate change-induced temperature fluctuations pose a significant threat to crop production, particularly in the Southern Hemisphere. This study investigates the transcriptome and physiological responses of rapeseed to post-flowering temperature increases, providing valuable insights into the molecular mechanisms underlying rapeseed tolerance to heat stress. Two rapeseed genotypes, Lumen and Solar, were assessed under control and heat stress conditions in field experiments conducted in Valdivia, Chile. Results showed that seed yield and seed number were negatively affected by heat stress, with genotype-specific responses. Lumen exhibited a 9.3% average seed yield reduction, while Solar showed a 28.7% reduction. RNA-seq analysis of siliques and seeds revealed tissue-specific responses to heat stress, with siliques being more sensitive to temperature stress. Hierarchical clustering analysis identified distinct gene clusters reflecting different aspects of heat stress adaptation in siliques, with a role for protein folding in maintaining silique development and seed quality under high temperature conditions. In seeds, three distinct patterns of heat-responsive gene expression were observed, with genes involved in protein folding and response to heat showing genotype-specific expression. Gene coexpression network analysis revealed major modules for rapeseed yield and quality, as well as the trade-off between seed number and seed weight. Overall, this study contributes to understanding the molecular mechanisms underlying rapeseed tolerance to heat stress and can inform crop improvement strategies targeting yield optimization under changing environmental conditions.

The various methods used to choose the profile shift coefficients, primarily the so-called equalizations, were based on assumed advantages without physical evidence proving them. In this paper a new calculation method is presented for determining profile shift coefficient. The procedure gives the pair of values ​​of the profile shift coefficients, in which case, under the given load, the resulting bending stress will be of the lowest possible value.

Climate change is expected to increase the frequency and severity of abiotic stresses that lead to loss of crop yield. We investigated the effect of salinity (S), short episodes of high temperature (HS) and combination of S+HS at the reproductive phase on dead pericarps properties and yield of the crop plant Brassica juncea. Three intervals of HS resulted in massive seed abortion; seeds from salt-treated plants germinated poorly. Pericarp extracts of salt-treated plants reduced seed germination of B. juncea; all pericarp extracts completely inhibited seed germination of tomato and Arabidopsis; removal of pericarp extracts restored seed germination. HS reduced all metabolites accumulated in dead pericarps, except for upregulation of isomaltose and cellobiose. Salt induced alteration in metabolite levels including increase in proline, reduction in TCA intermediates and changes in phytohormone levels. Proteome analysis revealed hundreds of proteins stored in dead pericarps whose levels and composition were altered under salt stress. The integration of metabolic and proteomic data showed that changes in metabolites were highly correlated with changes in proteins involved in their biosynthetic pathways. Thus, besides providing a physical shield for seed/embryo protection dead pericarps store beneficial substances whose levels, composition and biological function are altered under stress, further highlighting the elaborated function of dead organs enclosing embryos in seed biology and ecology. The detrimental effect of HS on crop production might have implications for global food security in the face of climate change.

Research Highlights: Data of advanced-age provenance tests were reanalyzed applying a new approach, to directly estimate the growth of populations at their original sites under individually generated future climates. The results reveal surprisingly high resilience potential of fir species. Background and Objectives: The growth and survival of silver fir under future climatic scenarios is insufficiently investigated at the xeric limits. The selective signature of past climate determining the current and projected growth was investigated to analyze the prospects of adaptive silviculture and assisted transfer of silver fir populations, and of the introduction of non-autochthonous species. Materials and Methods: Hargreaves’ climatic moisture deficit was selected to model height responses of adult populations. Climatic transfer distance was used to assess the relative drought stress of populations at the test site, relating these to the past conditions to which the populations had adapted. ClimateEU and ClimateWNA pathway RCP8.5 data served to determine individually past, current, and future moisture deficit conditions. Beside silver fir, other fir species from South Europe and the American Northwest were also tested. Results: Drought tolerance profiles explained the responses of transferred provenances and predicted their future performance and survival. Silver fir displayed significant within-species differentiation regarding drought stress response. Applying the assumed drought tolerance limit of 100mm relative moisture deficit, most of the tested silver fir populations seem to survive their projected climate at their origin until the end of the century. Survival is likely also for transferred Balkan fir species and for grand fir populations, but not for the Mediterranean species. Conclusions: The projections are less dramatic than provided by usual field assessments. Some results contradict generally accepted concepts. The method fills the existing gap between experimentally determined adaptive response and the predictions needed for management decisions. It also underscores the unique potential of provenance tests.

This paper conducts an extensive literature review focusing on the utilisation of crack tip plasticity as a crucial parameter in determining and enhancing crack growth models. The review encompasses a comprehensive analysis of various methodologies, predominantly emphasising numerical simulations of crack growth models while also considering analytical approaches. Although experimental investigations are not the focus of this review, their relevance and interplay with numerical and analytical methods are acknowledged. The paper critically examines these methodologies, providing insights into their advantages and limitations. Ultimately, this review aims to offer a holistic understanding of the role of crack tip plasticity in the development of effective crack growth models, highlighting the synergies and gaps between theoretical, experimental, and simulation-based approaches.

Pure-compression shells have been the central topic in the form-finding of shells. This paper studies tension-compression mixed type shells by utilizing a NURBS-based isogeometric form-finding approach that analyzes Airy stress functions to expand the possible plan geometry. A complete set of smooth version graphic statics tools is provided to support the analyses. The method is validated using examples with known solutions, and a further example demonstrates the possible forms of shells that the proposed method permits. Additionally, a guideline to configure a proper set of boundary conditions is presented through the lens of asymptotic lines of the stress functions.

Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6-8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving. Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-, IL-6, and neopterin). VGE exhibits a progressive reduction followed by an increase (p<0.0001) which parallels in-flammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min−1 (p<0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg-1 creatinine (p<0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.ml-1 (p<0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol−1 creatinine (p=0.005), respectively. The variation after each dive was held constant around 158.3 ± 6.9% (p = 0.021); 151.4 ± 5.7% (p <0.0001); 176.3 ± 11.9% (p<0.0001); and 160.1 ± 5.6% (p<0.001), respectively. When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of “first generation” pre-existing micronuclei.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Rats, including those of the Sprague Dawley strain, may kill mice. Because of this muridical behavior, it is standard practice in many research animal housing facilities to separate mice from rats (i.e., the predators) to minimize stress for the mice. We therefore tested the effect of cohousing on the stress levels of mice from either the C57BL/6J (BL6) or the CD1 strain and Sprague Dawley (SD rat) by determining their fecal corticosterone or cortisol metabolites (FCM) concentration and investigated how cohousing impacts a behavioral assay, i.e., conditioned place preference for intragenus (i.e., mouse-mouse or rat-rat) dyadic social interaction (DSI CPP) that had been shown be sensitive to social factors, especially to handling by humans. We found that the two delivery batches of BL6 mice or SD rats, respectively, had different stress levels at delivery that were statistically significant for the BL6 mice. Even so, the BL6 mice cohoused with rats had significantly increased FCM concentrations, indicative of higher stress levels, as compared to (1) BL6 mice housed alone or (2) BL6 mice at delivery. In contrast to their elevated stress levels, the attractiveness for contextual cues associated with mouse-mouse social interaction (DSI CPP) even increased in rat-cohoused BL6 mice, albeit nonsignificantly. Thus, cohousing BL6 mice and rats did not impair a behavioral assay in BL6 mice that had proved to be sensitive to handling stress by humans in our laboratory. SD rats cohoused with BL6- or CD1 mice and CD1 mice cohoused with SD rats showed DSI CPP that was not different from our previously published data on SD rats and BL6 mice of the Jackson- or NIH substrain obtained in the absence of cohousing. Our findings suggest that the effect of cohousing rats and mice under the conditions described above on their stress levels as opposed to their behavior might be less clearcut than generally assumed and might be overriden by conditions that cannot be controlled, i.e., different deliveries. Our findings can help to use research animal housing resources, which usually are limited, more efficiently.

Understanding the evolutionary role of environmentally-induced phenotypic variation (i.e., environmental plasticity) is an important issue in developmental evolution. One of the major physiological responses to environmental changes is cellular stress, which is counteracted by a generic stress reaction that detoxifies the cell, refolds proteins, and repairs DNA damage. In this paper, we elaborate on a previous finding suggesting that the cell differentiation cascade of human decidual stromal cells, a cell type critical for embryo implantation and the maintenance of pregnancy, evolved from a cellular stress reaction. We hypothesize that the stress reaction in these cells was elicited ancestrally through the inflammation caused by embryo attachment and invasion. We describe a model, Stress-Induced Evolutionary Innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types. After reviewing similarities and differences between SIEI and the “plasticity first hypothesis” (PFH) of evolution, we argue that SIEI is a distinct form of plasticity-based evolutionary change because it leads to the origin of novel structures rather than the adaptive transformation of a pre-existing character.

A home-built equipment will be presented able to measure thermal expansion and indentation up to 1100 oC. The principle of operation is similar to that of Rockwell hardness measurement. First, we apply a small load and measure the thermal expansion of the construction consisting of the sample holder quartz tube, the conical in-denter and the sample. Then we repeat the thermal cycle with such a high load that produces a deviation in thermal expansion already after 200-300 oC, compared to the previous thermal expansion measurement with low load. With increasing temperature, the indentation depth increases and at higher temperatures we already notice a contraction. The evolution of indentation depth as a function of temperature, d(T), we can obtain by sub-tracting the high load curve from the low load curve. Newly created phenomenological expressions will be tested to describe the thermal softening of pure metals and refractory HEAs. The results will be interpreted taking into account the allotropic transformations and temperature dependencies of elastic moduli. We are working on the instrument to extend the working temperature up to 1200 oC.

Alcohol effects on hepatic lipid metabolism through various mechanisms, leading synergistically to an accumulation of fatty acids (FA) and triglycerides. Obesity, as well as, the dietary fat [saturated fatty acids (FA) versus poly-unsaturated fatty acids (PUFA)] may modulate the hepatic fat. Alcohol inhibits adenosine monophosphate activated kinase (AMPK). AMPK activates peroxisome proliferators activated receptor a (PPARα) and leads to a decreased activation of sterol regulatory element binding protein 1c (SRABP1c). The inhibition of AMPK, and thus of PPARα results in an inhibition of FAs oxidation. This ß-oxidation is further reduced due to mitochondrial damage induced through cytochrome P4502E1 (CYP2E1) driven oxidative stress. Furthermore, the synthesis of FAs is stimulated through an activation of SHREP1. In addition, alcohol consumption leads to a reduced production of adiponectin in adipocytes due to oxidative stress and to an increased mobilization of FAs from adipose tissue and from the gut as chylomicrons. On the other side, the secretion of FAs via very low density lipoproteins (VLDL) from the liver is inhibited by alcohol. Alcohol also affects signal pathways such as early growth response 1 (Egr-1) associated with the expression of tumour necrosis factor  (TNF), and the mammalian target of rapamycin (mTOR) a key regulator of autophagy. Both have influence the pathogenesis of alcoholic fatty liver. Alcohol-induced gut dysbiosis is contributing to the severity of ALD by increasing metabolism of ethanol in the gut and promoting intestinal dysfunction. Moreover, pathogen associated molecular paterns (PAMPS) via specific Toll-like receptors (TLR) bacterial overgrowth is leading to the translocation of bacteria. Endotoxins, and toxic ethanol metabolites enter the enterohepatic circulation reaching the liver, inducing the activation of the nuclear factor kappa-B (NFB) pathway. Pro-inflammatory cytokines released in the process contribute to inflammation and fibrosis. In addition, cellular apoptosis is inhibited in the favor of necrosis.