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

Plant transcriptomes are an extremely dynamic entities shaped spatially and temporally by many intracellular and environmental cues. In this review, we first summarize the complexity and diversity of plant genomes and transcriptomes as a start point for the multitude of transcriptomic responses. Numerous alterations within various tissue and organ-specific transcriptomes as well as the most relevant transcriptomic responses associated with plant acclimation to selected abiotic and biotic stress conditions, from the current studies employing high-throughput transcriptomic analysis are widely discussed. Understanding changes within plant transcriptomes, revealed by in silico functional analysis, allows for the characterization of stress-affected genes and stress acclimatory mechanisms, as well as allows to perform plant metabolic engineering. The latter allow cultivars to produce more secondary metabolites in the future, which are often desirable substances in the biomedical industry. Accordingly, in this review special attention was also paid to characterize the potential of transcriptomic analyses of medicinal species, particularly to search for new cultivars. Extensive characterization of transcriptomic responses in stress would also result in the development of new cultivars that display physiological and molecular mechanisms that allow them to cope with adverse environmental conditions more adequately.

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetic helps to improve treatment decisions and sometimes also to avoid unnecessary exposure to potentially toxic immunosuppression. New Biomarkers led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is getting wider with a pipeline of promising new therapeutic agents with more sophisticated approaches. This review focuses on all aspects of entities that are associated with nephrotic syndromes with updated information on recent advances in each field. This includes podocytopathies (Focal Segmental Glomerulosclerosis and Minimal-Change Disease), Membranous Nephropathy, Membranoproliferative Glomerulonephritis, IgA-Nephropathy, Fibrillary Glomerulonephritis, Amyloidosis and monoclonal gammopathy of renal significance in the context of the nephrotic syndrome, but also renal involvement in systemic diseases, diabetic nephropathy, and drugs that are associated with nephrotic syndromes.

Plant growth regulators (PGRs) and deficit irrigation (DI) play a crucial strategic role in sustaining agricultural yield and reducing water stress in drought prone areas. The study was carried out in 2021-2022 to assess the impact of various PGRs (SA & NAA) & irrigation levels (60% Epan, 80 % Epan, and 100 % Epan) with DI & partial root drying (PRD) irrigation strategies. PGR application boosted fruit yields and demonstrated its significance in reducing water stress by lowering canopy temperature, maintaining higher relative water content in the leaves, modifying stomatal opening, and increasing photosynthetic rate. PGRs were used to assess the increased accumulation of total phenols, flavonoids, and improved antioxidant activity. Results indicated that exogenous use of PGRs like SA+NAA in conjunction with 80% irrigation levels increased fruit yield (31.97 and 40.38%) and water productivity (64.92 and 75.39%) for DI and PRD treatments, respectively. Thus standardizing irrigation and crop management practices including PGR application can be recommended to boost pomegranate productivity particularly in water-scarce environments.

Phosphite (Phi) has gained attention in agriculture due to its biostimulant effect on crops. This molecule has been found to benefit plant performance by providing protection against pathogens, improving yield and fruit quality, and improving nutrient and water use efficiency. It is still unclear how Phi enhances plant growth and protects against multiple stresses. It has been hypothesized that Phi acts by directly affecting the pathogens and interacting with the plant cellular components and molecular machinery to elicit defense responses. This study delves into elucidating the mechanisms underlying Phi’s beneficial effects on plants, revealing a complex interplay with fundamental signaling pathways. A RNA-seq study of Arabidopsis seedlings under optimal and limiting phosphate conditions helped us unveil Phi’s role in promoting plant growth by activating the expression of genes involved in the biosynthesis and signaling pathways associated with abscisic acid (ABA), salicylic acid (SA), and jasmonic acid (JA). Expression of ABA-related genes, known for their involvement in stress response and development regulation, is triggered by Phi treatment, contributing to enhanced resilience and growth. Simultaneously, the activation of the SA pathway, associated with defense responses, suggests Phi’s potential in bolstering plant immunity. Moreover, Phi influences JA biosynthesis and signaling, which are crucial for defense against herbivores and pathogens, thereby strengthening plants’ defenses. Our findings reveal a multifaceted mechanism through which Phi benefits Arabidopsis development. Understanding its intricate interplay with key signaling pathways opens avenues for leveraging Phi as a strategic tool to enhance plant resilience, immunity, and growth in agricultural and ecological contexts.

The Aspergillus genus comprises fungi that are widely distributed in nature. The Terrei section is particularly important due to its functions in recycling organic matter. Aspergillus hortae is a species from this section that has been isolated from clinical samples, but its role as a pathogenic agent is unclear. In this study, three clinical A. hortae isolates from Colombia, initially identified as A. terreus, were characterised by micro and macro-morphological analysis at 26°C and 37°C. A bioinformatic pipeline was used for molecular typing, which included analysis of whole genome sequences for accurate species identification. Susceptibility assays were also conducted using the microdilution broth method (EUCAST). It was confirmed that this species is intrinsically resistant to Amphotericin B with a minimum inhibitory concentration (MIC) of 2-4 mg/L, and is also thermotolerant. We obtained the in vitro susceptibility profiles for three azole drugs (MIC, 0.25-1 mg/L). The three isolates showed phylogenetic divergence from the reference genome strain. A mutation (M769K) in the MelA ortholog of a hypopigmented isolate, which had the lowest MIC value for AmB (2 mg/L), was identified. This study presents the morphological characterization, molecular typing through whole-genome analysis and identification of susceptibility profiles to azoles and amphotericin B of three clinical isolates of A. hortae from Colombia.

Circulating tumor cells (CTCs) are cells released from the primary tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice.

To enhance pomegranate production on marginal gravelly lands, standardized planting techniques were evaluated in an 8-year-old orchard. Trenching, wider pit excavation, pit digging, and auger digs with dimensions of 1 and 2 m were employed. Utilizing native soil from barren land, with or without spent wash, and mixing it with black soil up to 1 m deep, growth parameters, leaf nutrients, fruit production, and fruit quality were assessed. The trench and wider pit methods outperformed others, yielding greater above-ground biomass (>70.3 kg tree⁻¹), root biomass (>24.5 kg, tree⁻¹), and cross-sectional area (>3.30 m² tree⁻¹). These methods also produced longer roots (>4.0 m tree⁻¹) and higher leaf phosphorus (>0.28%) and potassium (>1.81%) levels, fruit juice content (>48.50%), and total soluble solids (>16.05°) compared to other planting methods. This resulted in higher and more sustainable fruit yield production under the trench and wider pit planting methods (>7.21 t ha⁻¹). Similarly, the native and black soil mixture produced healthy fruit trees, improved fruit quality, and sustainably higher fruit yield over the native soil alone. In summary, the trench and wider pit methods (2–3 m³), combined with a soil mixture, are recommended for sustainable, high-quality fruit production in shallow gravelly terrains, thereby improving food security and the livelihoods of farmers in arid regions.

Oxidative stress has been implicated in cellular senescence and aging, as well as in the onset and progression of many diverse genetic and acquired diseases and conditions. The search for biomarkers of oxidative stress has become relevant to many biomedical fields using many different methods and approaches. Fluorescence methodology is advantageous because of its simplicity and high sensitivity. Fluorescent probes are frequently used to investigate the role of reactive oxygen species in oxidative stress in experimental or clinical settings, often involving the use of flow cytometry and related single-cell based technologies. To assess the specific role of reactive oxygen species in oxidative stress studies by cytometric methodologies, it is essential to detect and characterize these species accurately. However, the detection and quantitation of individual intracellular ROS is still a challenge, but different and complementary strategies may focus on other endpoints of oxidative stress. In this review we present and discuss briefly the limitations and perspectives of such approaches. Based on our results, we also provide recommendations for proper design of cytometric studies of oxidative stress in order to prevent or minimize experimental errors..

In the last three decades the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because of their role in signalling acting. Here we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling both in physiological and pathological conditions.

The development of a rapid, sensitive, specific method for detecting foodborne pathogens is paramount in supplying safe food to enhance public health safety. Despite the significant improvement in pathogen detection methods, key issues are still associated with rapid methods, such as distinguishing living cells from dead, pathogenic potential or health risk of the analyte at the time of consumption, detection limit, and sample-to-result. The mammalian cell-based assays analyze pathogens' interaction with the host cells and are responsive to only live pathogens or active toxins. In this study, a human embryonic kidney (HEK293) cell line expressing Toll-Like Receptor 5 (TLR-5) and chromogenic reporter system (HEK dual hTLR5) was used for the detection of viable Salmonella in a 96-well tissue culture plate. This cell line responds to low concentrations of TLR5 agonist flagellin. Stimulation of TLR5 ligand activates nuclear factor-kB (NF-κB) - linked alkaline phosphatase (AP-1) signaling cascade inducing the production of secreted embryonic alkaline phosphatase (SEAP). With the addition of a ρ-nitrophenyl phosphate as a substrate, a colored end product representing a positive signal is quantified. The assay's specificity was validated with the top 20 Salmonella enterica serovars and 19 non-Salmonella spp. The performance of the assay was also validated with spiked food samples. The total detection time (sample-to-result), including shortened pre-enrichment (4 h) and selective enrichment (4 h) steps with artificially inoculated outbreak-implicated food samples (chicken, peanut kernel, peanut butter, black pepper, mayonnaise, and peach) was 15 h when inoculated at 1–100 CFU/25 g sample. These results show the potential of HEK-DualTM hTLR5 cell-based functional biosensors for rapid screening of Salmonella.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

The process of oxygenic photosynthesis is primarily driven by two multiprotein complexes known as photosystem II (PSII) and photosystem I (PSI). PSII facilitates the light–induced reactions of water–splitting and plastoquinone reduction, while PSI functions as the light–driven plastocyanin-ferredoxin oxidoreductase. In contrast to the highly conserved structure of PSII among all oxygen–evolving photosynthetic organisms, the structures of PSI exhibit remarkable variations, especially for photosynthetic organisms that grow in special environments. In this review, we make a concise overview of the recent investigations of PSI from photosynthetic microorganisms including prokaryotic cyanobacteria and eukaryotic algae from the perspective of structural biology. All known PSI complexes contain a highly conserved heterodimeric core; however, their pigment compositions and peripheral light-harvesting proteins are substantially flexible. This structural plasticity of PSI reveals the dynamic adaptation to environmental changes for photosynthetic organisms.

In prostate cancer, p53 maximizes apoptosis in response to severe DNA damage, not DNA replication stress. Here, we examined the apoptotic response of two glioblastoma cells, p53-wild type U87 and a p53-mutated T98G cell, for the same stresses. We ascertained that p53 intensified apoptosis in response to severe DNA damage, not DNA replication stress in glioblastoma. We further asked if p53-mediated apoptosis can be induced by cellular stress other than severe DNA damage. We analyzed two compounds, bortezomib and vorinostat, respective inhibitors of 26S proteasome and histone deacetylase, to evaluate their capacity to activate p53-mediated apoptosis. The cellular stress incited by bortezomib, not vorinostat, activated p53-mediated apoptosis. Next, we asked if the cellular stress generated by combining the two compounds had a synergistic effect on apoptosis. Our results demonstrated that doxorubicin with bortezomib or CFS-1686, or bortezomib with vorinostat have a significant synergistic effect on apoptosis only in p53-wild type cell. Under high stress, p53 translocates from cytosol into the nucleus to cause apoptosis possibly. Together, p53 maximizes apoptosis for cellular stress caused by severe DNA damage, disruption of protein turnover, and for the stress induced by drug combination including doxorubicin with bortezomib or CFS-1686, and bortezomib with vorinostat.

Ectopic expression of the MYB transcription factor of AmROSEA1 from Antirrhinum majus has been reported to change anthocyanin and other metabolites in several species. In this study, we found that overexpression of AmRosea1 significantly improved the tolerance of transgenic rice to drought and salinity stress. Transcriptome analysis revealed that a considerable amount of stress-related genes were affected by exogenous AmRosea1 during both drought and salinity stress treatments. These affected genes are involved in stress signal transduction, the hormone signal pathway, ion homeostasis and the enzymes that remove peroxides. This work suggests that the AmRosea1 gene is a potential candidate for genetic engineering of crops.

Background : Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis. However, Methods: We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy denoting acute myocarditis, with normal coronaries and valves. Tissue samples were processed for histology (H&E), immunohistochemistry for the evaluation of inflammatory infiltrates, immunostaining for alpha-sarcomeric-actin, junctional connexin-43, Ki-67, phosphorylated STAT3 (p-STAT3) and Western Blot (WB) for HMGB1. Frozen samples were analyzed with polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies. Results: NGCs were defined as small myocytes (diameter < 10 µm) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic α-sarcomeric actin and connexin 43. Their number/mm2 in relation with age and pathway of integration were evaluated. NGCs crossed the membrane and grew integrated within the empty necrotic myocytes. NGC mean diameter was 6.6 ± 3.34 vs 22.5 ± 3.11 µm adult cells; their number, in comparable LVEF, was 86.3 ± 10.3/mm2 in patients between 10 and 40 years; 50.4 ±13.8/mm2 in those between 41 and 60; 15.1 ± 5.7/ mm2 in those between 61 and 80; control NGC mean diameter was 0.2± 0.2/mm2. PCR was positive for viral genomes in 16% of cases; NGCs were not statistically different in viral and non-viral myocarditis. WB analysis revealed a higher expression of HMGB1 in myocarditis compared to myocardial controls. Conclusions: NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes consents preservation of cardiac structure and function.

Disruption of the in utero environment can have dire consequences on fetal growth and development. Intrauterine growth restriction (IUGR) is a pathological condition by which the fetus deviates from its expected growth trajectory, resulting in low birth weight and impaired organ function. The developmental origins of health and disease (DOHaD) postulates that IUGR has lifelong consequences on offspring well-being, as human studies have established an inverse relationship between birth weight and long-term metabolic health. While these trends are apparent in epidemiological data, animal studies have been essential in defining the molecular mechanisms that contribute to this relationship. One such mechanism is cellular stress, a prominent underlying cause of the metabolic syndrome. As such, this review considers the role of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation in the pathogenesis of metabolic disease in IUGR offspring. In addition, we summarize how uncontrolled cellular stress can lead to programmed cell death within the metabolic organs of IUGR offspring.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Liver fibrosis, a consequence of chronic liver damage or inflammation, is characterized by the excessive buildup of extracellular matrix components. This progressive condition significantly raises the risk of severe liver diseases like cirrhosis and hepatocellular carcinoma. The lack of approved therapeutics underscores the urgent need for novel anti-fibrotic drugs. Hepatic stellate cells (HSCs), key players in fibrogenesis, are promising targets for drug discovery. This study investigated the anti-fibrotic potential of Citrus hystrix DC. (KL) and its bioactive compound, β-citronellol (β-CIT), in a human HSC cell line (LX-2). Cells exposed to TGF-β1 to induce fibrogenesis were co-treated with crude KL extract and β-CIT. Gene expression was analyzed by Real-Time qRT-PCR to assess fibrosis-associated genes (ACTA2, COL1A1, TIMP1, SMAD2). The releasing of matrix metalloproteinase 9 (MMP-9) was measured by ELISA. Proteomic analysis and molecular docking identified potential signaling proteins and modeled protein-ligand interactions. Results showed that both crude KL extract and β-CIT suppressed HSC activation genes and MMP-9 levels. The MAPK signaling pathway emerged as a potential target of β-CIT. This study demonstrates the ability of KL extract and β-CIT to inhibit HSC activation during TGF-β1-induced fibrogenesis, suggesting a promising role of β-CIT in anti-hepatic fibrosis therapies.

Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the action potential and contraction of the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes via cooperative mechanisms of mechano-calcium-electric feedback are essential to produce the differences in Ca²⁺ transients and contraction profiles and may further enhance transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in afterload than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.

Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anticancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM, for 24/48 hours. We performed immunofluorescence experiments by means of confocal microscopy and Western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response. Moreover, HT29 cells treated with metformin were analyzed by flow cytometry assay to detect the cell apoptosis rate. The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of nuclear factor E2–related factor 2 (NRF-2) and nuclear factor–kappa B (NF-κB). The effects of metformin on HT29 cells were dose- and time-dependent. These results are very intriguing, since metformin is emerging as a multifaceted drug: it has a good safety profile and is associated with low cost, and it might be a promising candidate for the prevention or treatment of colorectal cancer.

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia giving rise to oligodendrocytes, the myelin forming cells in the central nervous system (CNS). While OPCs are highly proliferating during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated, they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar, a barrier mainly formed by reactive astrocytes, microglia, and the deposition of inhibitory extracellular matrix components. If, on one hand, glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.

Background: The COVID-19 pandemic led to rapid growth in telemental health services and investment in digital mental health technologies. Digital mental health technologies could expand access to mental health care amid increasing provider deficit by providing tools for expedited psychiatric symptom assessment and treatment augmentation. This systematic review explores the recent evidence for the use of scalable digital tools, including virtual reality, neurofeedback training, wearables, mobile apps, digital phenotyping, and machine learning for PTSD symptom assessment, diagnosis, and treatment. Methods: A PubMed search identified studies on digital technologies with current or future potential for scalability (accessible through a small, digital device without the virtual or in-person presence of a mental health care provider)–and PTSD diagnosis, symptom assessment, or symptom treatment as the primary outcome. Thirty-five studies inform this review. Results: Virtual reality exposure therapy is efficacious for combat-related PTSD treatment. Conclusions of studies investigating apps and neurofeedback training are limited by low sample size and methodological heterogeneity. Machine learning models demonstrate capability in detecting PTSD symptoms via passively collected data from smartphones, wearables, and actively collected data from patient speech, writing, and videos, but standardization of data collection and modeling are needed before application to clinical settings. Conclusions: Advancements in scalable digital tools could address barriers in healthcare access and improve patient engagement by providing asynchronous assessment and treatment augmentation. Future research utilizing diverse patient populations in standardized controlled trials is needed to determine evidence-based protocols for implementation.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase small molecule glues, but developing new small molecule drugs for each patient is not feasible currently. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

The unique structure of G4.0 PAMAM dendrimers allows the drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin (DOX) were optimized. The physicochemical properties of the system were monitored using DLS, CD, and fluorescence spectroscopy. The QCM-D method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the ITC isotherm. Fluorescence spectra and release curves identified reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of G4.0-DOX was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is important from a therapeutic point of view.

Von Hippel-Lindau disease (VHL) is a multiple organ neoplastic syndrome with autosomal dominant transmission, complete penetrance, and variable expression caused by mutations in the VHL gene. Although VHL disease is hereditary in many cases, new mutations cause up to 20 % of the incidence. Mutations in VHL may cause the development of cysts and tumors in many organs, including brain and spinal cord hemangioblastoma, renal cell carcinoma (RCC), retinal heman-gioblastoma (RH), pheochromocytoma, epididymal and broad ligament cystadenomas, endo-lymphatic sac tumor, pancreatic neuroendocrine tumors, and renal and pancreatic cysts. VHL is a syndrome associated with functional inactivation of the Von Hippel–Lindau protein (pVHL). pVHL is a tumor suppressor mainly known for its role as a regulator of hypoxia-inducible factor (HIF) activity. The prevalence of VHL disease is between 1 in 39 000 and 1 in 91 000 individuals in different regional populations. Here, we review the etiology, epidemiology, pathophysiology, genetics, clinical manifestations, diagnosis, and current treatments, as well as the molecular aspects of this disease. We also discuss the animal models used to study this disease, VHL biomarkers, and current VHL clinical trials for VHL according to NIH.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

The question of what generates conscious experience has mesmerized thinkers since the dawn of humanity, yet its origins remain a mystery. The topic of consciousness has gained traction in recent years, thanks to the development of large language models that now arguably pass the Turing test, an operational test for intelligence. However, intelligence and consciousness are not related in obvious ways, as anyone who suffers from a bad toothache can attest - pain generates intense feelings and absorbs all our conscious awareness yet nothing particularly intelligent is going on. Still, in the hard sciences, this topic is frequently met with skepticism because to date no protocol to measure the content or intensity of conscious experiences in an observer-independent manner has been agreed upon. Here we present a novel proposal: Conscious experience arises whenever a quantum mechanical superposition forms. Our proposal has several implications: First, it suggests that the structure of the superposition determines the qualia of the experience. Second, quantum entanglement naturally solves the binding problem, ensuring the unity of phenomenal experience. Finally, a moment of agency may coincide with the formation of a superposition state. We outline a research program to experimentally test our conjecture via a sequence of quantum biology experiments. Applying these ideas opens up the possibility of expanding human experience through brain-quantum computer interfaces.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research highlights the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between microbiome and esophageal carcinogenesis, focusing on eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

Helicobacter pylori infection constitutes a silent pandemic of global concern. In the last decades, the alarming increase of multidrug resistance evolved by this pathogen has led to a marked drop in the eradication rates of traditional therapies worldwide, encouraging scientific community to discover and develop new antimicrobial strategies. In the present work, we identified a battery of novel drug-like HsrA inhibitors with MIC values ranging from 0.031 to 4 mg/L against antibiotic-resistant strains of H. pylori. Most of these novel antimicrobials exhibited minor effects against both Gram-negative and Gram-positive species of human microbiota. The most potent anti-H. pylori candidate demonstrated a high therapeutic index, additive effect in combination with metronidazole and clarithromycin, as well as a strong antimicrobial action against Campylobacter jejuni, another clinically relevant pathogen of phylum Campylobacterota. Transcriptomic analysis suggested that in vivo inhibition of HsrA triggered lethal global disturbances in H. pylori physiology, including the arrest of protein biosynthesis, malfunction of respiratory chain, detriment in ATP generation, and oxidative stress. The novel drug-like HsrA inhibitors described here constitute valuable candidates to a new family of narrow-spectrum antibiotics that allow overcoming the current resistome, protecting from dysbiosis, and increasing therapeutic options for novel personalized treatments against H. pylori.

Kisspeptin, a key neuropeptide derived from the KISS1 gene, is renowned for its critical role in regulating the hypothalamic-pituitary-gonadal axis and reproductive hormone secretion. Beyond its primary function in reproductive biology, emerging research has illuminated its influence in various cancers, mediating significant effects through its interaction with the G-protein coupled receptor, Kisspeptin receptor. This interaction has been implicated in modulating cellular pro-cesses such as proliferation and metastasis, making it a potential target for therapeutic interven-tion. Our study initially screened ten kisspeptin-10 analogs through cytotoxic effects of kisspep-tin-10 (KP10) and its analogs in several cancer types, including cervical, prostate, breast, and gastric cancers, with a particular focus on cervical cancer where the most profound effects were observed. Further exploration using kinase array assays revealed that these analogs specifically alter key kinases involved in cancer progression. Migration assays demonstrated a substantial decrease in cell motility, and Bioluminiscence Resonance Energy Transfer assays confirmed these analogs strong interactions with the kisspeptin receptor. Overall, our results indicate that these KP10 analogs not only hinder cervical cancer cell proliferation but also curtail migration through targeted modulation of kinase signaling, suggesting their potential as therapeutic ayfgents in managing cervical cancer progression. This comprehensive approach underscores the therapeutic promise of exploiting kisspeptin signaling in cancer treatment strategies.

Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin and MMP2, enhancing drug resistance and migration in recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights to the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.

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.

Background: Depression presents with altered energy regulation and neural plasticity. Previous electroencephalography (EEG) studies showed that practice increases power in beta range (13-30 Hz) in healthy subjects but not in those with impaired plasticity. Here, we ascertain whether depression presents with alterations of spectral activity and connectivity before and after practice. Methods: We used publicly available resting state EEG (64 electrodes) of 122 subjects. Based on Beck Depression Inventory (BDI) score, they were assigned to either high BDI (hBDI, BDI&gt;13, N=46) or control (CTL, BDI&lt;7, N=75) group. We analyzed spectral activity, theta-beta and theta-gamma phase-amplitude coupling (PAC) of EEG recorded before and after a learning task. Results: At baseline, compared to CTL, hBDI group exhibited greater beta power over fronto-parietal regions and gamma over right parieto-occipital area. After practice, increases in all frequency ranges were observed only in CTL. Theta-beta and theta-gamma PAC were greater in hBDI before the task but not after the task. Conclusions: The lack of substantial post-task growth of beta power in depressed subjects likely represents power saturation due to greater baseline values. We speculate that inhibitory/excitatory imbalance, altered plasticity mechanisms, and energy dysregulation present in depression may contribute to this phenomenon.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Magnetogenetics emerges as a transformative approach for modulating cellular signaling pathways through the strategic application of magnetic fields and nanoparticles. This technique leverages the unique properties of magnetic nanoparticles (MNPs) to induce mechanical or thermal stimuli within cells, facilitating the activation of mechano- and thermosensitive proteins without the need for traditional ligand-receptor interactions. Unlike traditional modalities that often require invasive interventions and lack precision in targeting specific cellular functions, magnetogenetics offers a non-invasive alternative with the capacity for deep tissue penetration and the potential for targeting a broad spectrum of cellular processes. This review underscores magnetogenetics' broad applicability, from steering stem cell differentiation to manipulating neuronal activity and immune responses, highlighting its potential in regenerative medicine, neuroscience, and cancer therapy. Furthermore, the review explores the challenges and future directions of magnetogenetics, including the development of genetically programmed magnetic nanoparticles and the integration of magnetic field-sensitive cells for in vivo applications. Magnetogenetics stands at the forefront of cellular manipulation technologies, offering novel insights into cellular signaling and opening new avenues for therapeutic interventions.

We explores the relational, dynamic elements of Complex Buildings, a type of architecture designed to incubate uses, located in urban areas with high housing density. The uses of Complex Buildings concern different elements, including the network of agents using or managing them, the environment, and the activities and functions that take place occasionally, temporarily or permanently. Data was gathered through ethnographic research lasting 6 months and a chronotopian approach was used to describe time and space. We analyzed and discussed the interaction of the elements of Complex Buildings through a cellular automaton model, a computational method that simulates the growth of complex systems. It was used here to generate patterns that suggest configurations of uses that can optimize management and therefore increase economic and social capital. The cellular automaton model was also used to develop an abstraction of the Centquatre, a public cultural center in Paris. This center is a good example of a Complex Building, being based on a public-private partnership and having an architectural configuration designed to host a wide range of art, social and productive activities. The building includes a large central space used as an urban public area open to different types of people. The importance of this case study lies in its capacity to produce economic value by combining different uses, and also by welcoming different people to the public space. Regarding the building as a living organism, the cellular automaton model reveals the determinant nature of the concepts of configuration, compatibility of uses and economic value generated by the presence of people. We argue that this approach makes it possible to show that the space-time design and public space dimensions are determinant factors in Complex Buildings.

Background: Bacteria, among the earliest life forms on Earth, are integral to both human health and environmental ecosystems. They contribute to essential processes such as digestion, nutrient absorption, and immune defense, and play key roles in the biogeochemical cycles that sustain life. Objective: This paper explores the indispensable role of bacteria in human life and environmental health, emphasizing their contributions to digestion, nutrient absorption, immune protection, and ecosystem functioning. It also discusses advances in understanding the human microbiome and their implications for health and therapeutic interventions. Methods: The study reviews existing literature on the human microbiome, probiotics, and the role of bacteria in environmental nutrient cycling. It analyses experimental evidence and case studies, particularly focusing on the impact of fecal microbiota transplantation (FMT) as a therapeutic tool. Metagenomic analysis techniques are examined to highlight the diversity and functionality of gut bacteria. Results: Bacteria are found to be essential for breaking down food, providing vital nutrients, and protecting against pathogens. They play a critical role in maintaining a healthy immune system and are involved in the biogeochemical cycles necessary for ecosystem health. Metagenomic analysis reveals significant variations in bacterial populations associated with health and disease, emphasizing the importance of a balanced microbiota. FMT shows promise as an effective treatment for various diseases, including gastrointestinal, metabolic, and neurological disorders. Conclusions: Bacteria are crucial for human health and environmental stability. Maintaining a balanced microbiota is vital for overall well-being, and interventions such as probiotics and FMT can offer significant health benefits. Future research should focus on further understanding the complex interactions between bacteria and their hosts to develop targeted therapies for various health conditions.

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

Age is the primary risk factor for neurodegenerative diseases such as Alzheimer’s and Huntington’s disease. Alzheimer’s disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer’s, Huntington’s, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling proteotoxicity in Alzheimer’s and Huntington’s disease-related, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO) delays age-associated paralysis in both models. This effect on paralysis was independent of protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event liking HAAO knockdown to delayed paralysis. This work demonstrates potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.

Although, promotion of urbanization culture in recent decades has made inevitable development of cities in the world, however, the development can be guided in a direction that leave, to the extent possible, minimum socioeconomic and environmental impacts. For this, it is required to first forecast auto-spreading orientation of cities and suburbs in rural areas over time and then avoid shapeless growth of cities. This paper is an attempt to develop a dynamic hybrid model based on logistic regression (LR), Markov chain (MC), and cellular automata (CA) for prediction of future urban sprawl in fast-growing cities. The model was developed using 12 widely-used urban development criteria, whose significant coefficient was determined by logistic regression, and validated by relative operating characteristic (ROC) analysis. The validated model was run in Guilan, a tourist province in northern Iran with a very high rate of urban development. For this, changes in the area of urban land use were detected over the period of 1989 to 2013 and then, future sprawl of the province was forecasted by the years 2025 and 2037. The analysis results revealed that the area of urban land use was increased by more than 1.7 % from 36012.5 ha in 1989 to 59754.8 ha in 2013, and the area of Caspian Hyrcanian forestland was reduced by 31628 ha. The results also predicted an alarming increase in the rate of urban development in the province by the years 2025 and 2037, during which urban land use is predicted to develop 0.9 % and 1.38 %, respectively. The development pattern is expected to be uneven and scattered, without following any particular direction. The development will occur close to the existing or newly-formed urban basements as well as around major roads and commercial areas. This development, if not controlled, will lead to the loss of 13863 ha of Hyrcanian forests and if the trend continues, 21013 ha of Hyrcanian forests and 20208 ha of Barren/open lands are expected to be destroyed by the year 2037. In general, the proposed model is an efficient tool for the support of urban planning decisions and facilitates the process of sustainable development of cities by providing decision-makers with an overview on future development of cities where the growth rate is very fast.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

The Mononuclear Phagocyte System includes monocytes, macrophages, some dendritic cells and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow haematopoietic progenitors, tissue location and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells, through trophic, clearance and cytocidal functions. During evolution they contributed to innate host defense before effector mechanisms of specific adaptive immunity emerged. Mouse macrophages appear at midgestation and are distributed throughout the embryo to facilitate organogenesis and clear cells undergoing programmed cell death. Yolk sac-, AGM- and foetal liver-derived tissue resident macrophages persist throughout postnatal and adult life, supplemented by bone marrow-derived blood monocytes, as required after injury and infection. Nobel awards to Elie Metchnikoff and Paul Ehrlich in 1908 drew attention to cellular phagocytic and humoral immunity, respectively. In 2011, prizes were awarded to Jules Hoffmann and Bruce Beutler for contributions to innate immunity and to Ralph Steinman for discovery of Dendritic Cells and their role in antigen presentation to T lymphocytes. We trace milestones in the history of mononuclear phagocyte research from the perspective of Nobel awards bearing directly and indirectly on their role in cellular immunity.

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.

Helicobacter pylori is a gastric oncopathogen that infects over half of the world’s human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.

Kynurenic acid (KYNA), a tryptophan metabolite, is believed to exert neuromodulatory and neuroprotective effects in the brain. The study aimed to examine the KYNA’s capacity to modify gene expression and the activity of cellular antioxidant enzymes in specific structures of the sheep brain. Anestrous sheep were infused intracerebroventricularly with two KYNA doses: lower (4×5 μg/60 μL/30 min, KYNA20) and higher (4×25 μg/60 μL/30 min, KYNA100) at 30min intervals. The abundance of superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPx1) mRNA, as well as enzyme activities (µM/µg of protein), were determined in the hypothalamic medial-basal (MBH) and preoptic (POA) areas, and in the hippocampal CA1 field. Both doses of KYNA caused a decrease (P&lt;0.01) in the expression of SOD2 and CAT mRNA in all structures examined compared to the control group (except for CAT in the POA at the KYNA100 dose). Furthermore, lower levels of SOD2 mRNA (P&lt;0.05) and CAT mRNA (P&lt;0.01) were found in the MBH and POA and in the POA and CA, respectively, in sheep administered with the KYNA20 dose. Different stimulatory effects on GPx1 mRNA expression were observed for both doses (P&lt;0.05-P&lt;0.01). KYNA exerted stimulatory, but dose-dependent effects on SOD2, CAT and GPx1 activities (P&lt;0.05-P&lt;0.01) in all brain tissues examined. The results indicate that KYNA may influence the level of oxidative stress in individual brain structures in sheep by modulating the expression of genes and activity of at least SOD2, CAT and GPx1. The present findings also expand the general knowledge about the potential neuroprotective properties of KYNA in the central nervous system.

Worldwide the severity of abiotic stress like heat, drought, salinity, cold, waterlogging, etc. are being increased because of global warming. Wheat crops must adapt to harsh environments through physiological, molecular, and genetic manipulation. Because of abiotic stress, reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced in wheat plants break down DNA and RNA bases, protein, lipid, and other macro- and micromolecules, resulting in stunted growth and yield decline. Abiotic stress also induces the crop's molecular functions, physiological, biological, and cellular processes, and their compositions. Different stressors like high light intensity, heat, drought, and salinity also impair photosynthesis damaging various pigments. Antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), etc. synthesized in harsh environments can ameliorate ROS/RNS produced in oxidative stress. Under abiotic stress, heat shock proteins (HSPs) heat shock transcription factors (HSFs) in heat stress, and dehydration-responsive element binding proteins (DREBs) in drought stress are activated to synthesize proteins to mitigate the deleterious effects of those stressors. Na⁺ exclusive genes (NAX1, NAX2) and Na⁺/H⁺ (K⁺) antiporter genes (NHX1, NHX2) hinder those ions from uptake into leaf sheaths and blades of wheat resulting in the declination of salinity in plants. Exogenous hormones like gibberellic acid, salicylic acid, and melatonin, etc., and osmoprotectants like proline, and gene manipulation in plants through genetic engineering are being employed to mitigate the toxic effects of abiotic stress on plants, as portrayed in many literatures. The review depicts how abiotic stress affects phenotypic, physiological, and molecular structures and functions of wheat crops, and their mitigation strategies to lessen their noxious effects on wheat.

Drought negatively affects the growth and development of barley. To explore the genetic variation in barley under drought stress, ten breeding genotypes were tested using polyethylene glycol-6000 to simulate drought conditions. We observed that drought stress adversely affected germination-related traits across all barley genotypes and this impact varied between genotypes, suggesting genotype-specific drought tolerance. The drought tolerance index was an ideal criterion for selecting drought-tolerant genotypes as it well characterized the gradient responses of barely genotypes to drought stress. Based on this indicator, genotype OB1878-ON-50 is recommended as a significant germplasm resource for breeding programs under lower precipitation conditions due to its superior tolerance to drought stress.

This literature review provides an in-depth exploration of the research conducted on the investigation and measurement of residual stress (RS) in Wire Arc Additive Manufacturing (WAAM) products, particularly focusing on how process parameters influence the phenomenon. RS plays a crucial role in determining the mechanical behavior and structural integrity of WAAM components. This review article gives an understanding of the relationship between process parameters and RS to optimize the WAAM processes and ensure the durability of the final products. It also summarizes key findings, measurement techniques, challenges, and future directions in this evolving field. The review also analyzes a measurement of RS in the products of WAAM as a function of process parameters depending on examining various research studies, techniques, and methodologies employed in their studies. Experimental measuring techniques and numerical analysis of RS to determine the impacts of RS in mechanical response in products of WAAM were discussed. By offering a comprehensive overview of current research trends and insights, this review serves as a valuable resource to guide future investigations, fostering the advancement of WAAM as a robust and efficient manufacturing technology.

Automatic and blind parameter estimation based on the inherent features of wireless signals is a major research area due to the fact that these techniques lead to the simplification of receivers, especially in terms of coarse synchronization, more importantly reduce down the signaling load at the control channels. Thus, in the literature many techniques are proposed to estimate a vast set of parameters including modulation types and orders, data and chip rates, phase and frequency offsets and so on. In this paper, a cyclostationary feature detection based method is proposed to estimate the carrier numbers and carrier spacing of carrier-aggregated direct sequence spread spectrum cellular signals blindly. The particular chip rate of the signal is also estimated through the process jointly. In the paper, after the proposed method is formulated, the measurement setup which is developed to collect the data for the validation of the proposed method is introduced. The measurement results are post-processed for performance analysis purposes. To that end, the method is investigated in terms of SNR values, different channel conditions, and measurement durations. Furthermore, the performance of the proposed method is compared with that of energy detection. Measurement results indicate superior performance of the proposed method under significant wireless channel impairments and in low-SNR regions.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

As the global population ages, the prevalence of neurodegenerative diseases has become a major public health concern. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks—such as genomic instability, telomere attrition, and neuroinflammation—and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.

The arsRBC operon encodes a 3-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic respectively. Previous research in Agrobacterium tumefaciens 5A demonstrated ArsR has regulatory control over a wide range of metal related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (AsIII) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during AsIII stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain, ArsR, and arsenic specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.

Stress is a natural yet potentially harmful aspect of human life, necessitating effective management, particularly during overwhelming experiences. This paper presents a scoping review of personalized stress detection models using wearable technology. Employing the PRISMA-ScR framework for rigorous methodological structuring, we systematically analyzed literature from key databases including Scopus, IEEE Xplore, and PubMed. Our focus was on biosignals, AI methodologies, datasets, wearable devices, and real-world implementation challenges. The review presents an overview of stress and its biological mechanisms, details the methodology for the literature search, and synthesizes the findings. It shows that biosignals, especially EDA and PPG, are frequently utilized for stress detection and demonstrate potential reliability in multimodal settings. Evidence for a trend towards deep learning models was found, although the limited comparison with traditional methods calls for further research. Concerns arise regarding the representativeness of datasets and practical challenges in deploying wearable technologies, which include issues related to data quality and privacy. Future research should aim to develop comprehensive datasets and explore AI techniques that are not only accurate but also computationally efficient and user-centric, thereby closing the gap between theoretical models and practical applications to improve the effectiveness of stress detection systems in real scenarios.

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

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

Microsporidia are intracellular parasites infecting a wide range of vertebrates and invertebrates. In bees, they cause a diarrheal disease called nosematosis, which represents a growing problem contributing to the decline of bee colonies. This parasitic disease infects the gastrointestinal tract of bees, disrupts their immune system, weakens them, and shortens their lifespan. There are two known species of this microsporidial parasite with a global distribution: Vairimorpha apis and Vairimorpha ceranae, with current research indicating that the species V. ceranae is gradually replacing V. apis. In this study, we focused on the detection and occurrence of Vairimorpha spp. in bee colonies kept in different environments, as well as on comparing the impact of hive location on its occurrence. The methods used included sampling from winter bee carcasses, microscopic examination of bee gut contents, and subsequent molecular duplex PCR analysis. Altogether, we examined 82 hives located at 4 different sites and focused on the impact of transportation as an abiotic factor disturbing bees leading to the development of Vairimorpha spp. disease. The results indicate an increased occurrence of this parasite in hives located in urban sites and hives situated in intravillage locations, which may be attributed to transportation and associated vibrations as an abiotic stress factor. Detection revealed that all samples were positive for Vairimorpha ceranae.

This study investigates stress perceptions, somatization, and coping strategies among 271 nursing and dentistry (n=126 and n=145, respectively), undergraduate and postgraduate students. For the study, an e-questionnaire was designed in a two-step process, uploaded in Google Forms and staying open for submissions during February 2024 in the School of Health Sciences, National and Kapodistrian University of Athens. In our sample, predominantly female (68.60%), the majority were undergraduates (80.10%). Females reported higher stress somatization (M=10.22, SD=5.23) compared to males (M=7.94, SD=6.14), with a moderate effect size (Cohen’s d=0.412, p

The problems of modeling the human bladder and its stress-strain state under external static influence were considered. A method for identification of the anisotropic biomechanical characteristics of bladder tissue was proposed. A FEM model was created, which accepts into regard that the bladder is surrounded by fiber and affected by surrounding organs, and partially protected by pelvic bones. The model considered the presence of constant hydrostatic pressure on the walls of the bladder when it is full. It has been shown that isotropic mechanical characteristics of biological tissue can be used for studying the deformed state of a filled bladder if the filled bladder 300 ml is considered as initial non-deformed stage. This was shown by modeling and verification the effect of the external static force on the bladder. Numerical experiments were conducted based on the constructed model. To validate the results obtained, a series of natural experiments on the effect of external pressure on the bladder under ultrasound control was conducted. In the future, it is planned to use the constructed model to study rupture deformations of the bladder under the influence of static and dynamic loads.

The main purpose of the study was to study the effects of a specific rowing ergometer training program on the athletic performance of young adolescents (n=56; 11.73 ± 1.4 years old) com-pared to a workout based on general strength training. Eight-week training program was im-plemented, with four sessions per week and two-hours per session. Sample was divided in two groups: a control group (CG) that performed circuit training with exercises aimed at building general strength and an experimental group (EG) who focused on specifically training on a rowing ergometer (rowing machine). The data obtained in a rowing meter test over the compe-tition distance were analyzed to obtain the average power attained (W) at the beginning of the training, at the middle (4 weeks), at the end of the training (8 weeks) and one year after the ex-perimentation. The results show that, although both forms of training improve the average W obtained in both categories, the EG subjects (+29.94W) obtained better averages in all phases of the study compared to the CG (+5.88W). Furthermore, this increase was greater in male rowers (+ 34.06W) than in female rowers (+24.54W). These results reveal that a specific rower rowing ergometer training program has a significant effect than a general strength program and these effects can even be observed a year after the intervention.

The amino acid proline accumulates in plants during abiotic stresses such as drought and salinity and is considered a reliable marker of environmental stress. While its accumulation is well established, its precise role in stress tolerance and its underlying molecular mechanism remain less clear. To address these issues, we performed a meta-analysis - a robust statistical technique that synthesizes results from multiple independent studies while accounting for experimental differences. We focused on 16 physiological and morphological parameters affected by drought and salt stress in transgenic plants expressing proline metabolic genes. For each parameter, we calculated the effect size as the response ratio (RR), which represents the logarithm of the mean value in the transgenic group over the mean value of the control group (lnRR). Under stress, most parameters exhibited significantly higher response ratios in the transgenic group, confirming the beneficial effects of proline during drought and salt stress. Surprisingly, under non-stressed conditions, most stress markers showed no significant differences between transgenic and non-transgenic plants, despite elevated proline levels in the former. These results suggest that the benefits of proline may be related to proline catabolism or may only become apparent during stress, possibly due to interactions with reactive oxygen species (ROS), which accumulate predominantly under stress conditions.

Students studying dentistry and nursing experience anxiety daily, which affects both their general well-being and academic achievement. Anxiety is exacerbated by several circumstances, such as stressors in one's personal life, clinical environment exposure, and academic expectations. To effectively regulate anxiety and support students' achievement, treatments that take these elements into account must be designed. In this study, 271 students from the National and Kapodistrian University of Athens, Greece's departments of dentistry and nursing were polled. Being the following resources, participants filled out an electronic questionnaire that was uploaded to Google Forms and assessed their levels of stress, anxiety, depression, resilience, hope, and spiritual well-being: a) the Depression, Anxiety, Stress Scale (DASS-21), b) the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-12), c) the Adult Hope Scale (AHS), d) the Resilience Assessment Questionnaire (RAQ8), and e) the Brief Resilience Scale (BRS). Additionally, demographic data was gathered, such as gender, educational attainment, family income, and country of origin. Statistical analyses were performed to investigate the relationships between the variables, including hierarchical multiple linear regression and t-tests. The sample consisted of 271 students from the Department of Nursing (n=126, 46.5%) and Dentistry (n=145, 53.5%), with 68.60% of them being female, 80.10% being undergraduate students, and 48.30% being from Athens, the country's capital. Comparatively speaking, 74.50 percent of nursing students were female, while 62.80% of dental students were. Compared to dental students (2.10%), nurses (40.50%) participated in postgraduate studies at a higher rate. Compared to dental students (44.80%), nursing students reported a household income of just 13.90%, which is much less than €35,000. Anxiety was reported by 51.30% of participants overall, with dental students reporting higher anxiety than nursing students. Higher family wealth was associated with reduced stress levels, while female undergraduate students reported higher levels of anxiety than their male counterparts. Hope was a strong predictor of resilience, but stress and worry had a negative correlation. Promoting students' well-being and academic success requires effective stress-reduction and resilience-building techniques aimed to not only improve student performance but also support future healthcare professionals' personal sustainability and holistic growth.

Chronic stress, culminating in burnout, evolves gradually and is notoriously difficult to detect due to vague symptoms and individuals' hesitance to acknowledge their struggles. To expedite the identification and recognition of this condition, enabling timely psychological intervention, the integration of Artificial Intelligence (AI) is increasingly considered. This research does not assert the feasibility of an AI system managing all aspects of chronic stress's impact. However, it highlights the capability of current technology to detect stress indicators based on quantifiable data like Heart Rate (HR) and organizational climate dimensions. Although other physiological markers such as oximetry, skin galvanic response, and EKG have been explored, they have not shown reliable differentiation between stress and joy. Focused on the unique context of school principals in the Bedouin regions of Israel, this study investigates the interplay between HR, organizational climate, and stress levels. It introduces a novel application of a fuzzy logic tool that combines HR and organizational climate metrics to aid in stress diagnosis. This tool incorporates the psychologist's expertise to provide real-time data crucial for developing effective coping strategies. While the AI-supported fuzzy system does not replace professional psychological intervention, it significantly enhances the speed of condition identification and intervention planning, thus shortening the response time to stress-related issues in educational leadership within culturally specific settings. The application of such AI-driven tools is pivotal for sustaining the well-being and effectiveness of educational leaders, thereby supporting the broader goal of educational sustainability.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Immune responses to influenza (flu) antigens reflect memory to prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed “original antigenic sin” or more recently “immune imprinting” and “seniority”. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccina-tions. A brief history of antibody generation theories is presented culminating in new findings about the immune-network theory suggesting that a network of clones exists between an-ti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells like natural killer (NK) cells and macrophages are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes are described. New vaccines in development are mentioned along with the results of some clinical trials. The manu-script concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and memory loss. Oxidative stress (OS) has emerged as a central element in the pathophysiology of AD, linking various pathological features including amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review comprehensively examines the role of OS in AD, focusing on the mechanisms of reactive oxygen species (ROS) production, mitochondrial dysfunction, and their impact on neuronal integrity. Additionally, the review highlights recent advances in antioxidant therapy. Elevated ROS levels in the aging brain exacerbate oxidative damage to lipids, proteins, and DNA, contributing to neuronal atrophy and synaptic loss. Mitochondrial dysfunction further amplifies OS, disrupting cellular energy metabolism and promoting neurodegeneration. Despite the strong association between OS and AD, antioxidant therapies have shown inconsistent clinical outcomes. Emerging strategies targeting offer promising avenues for therapeutic intervention. This review highlights the need for a multifaceted approach in understanding and mitigating OS-related damage in AD, aiming to pave the way for more effective treatments and improved patient outcomes.

Salinity stress emerges as an important menace to global food security, particularly affecting susceptible crops such as common bean plants (Phaseolus vulgaris L.). The disruption of ion balances caused by salt stress withing plants cells reduces water and nutrient absorption, and hampers growth and productivity. Sacchorhiza polyschides, a brown macroalga rich in essential elements, and macrominerals, has drawn attention as a natural biostimulant, being a potential remedy to bolster crop resilience against salt stress. This study delves into the effect of water extracts of Sacchorhiza polyschides (SPE) across varying concentrations (1%, 2%, and 5%) in common bean plants under salt stress (68.4 mM NaCl) conditions. Two different methods of application were used: by spraying the aerial part of the plant or by irrigation together with the watering solution. The effects of both systems of application were studied on the aerial parts of the plants. SPE exhibited significant enhancements in morphological parameters, chlorophyll content, carbon-nitrogen activities, and antioxidant enzymatic system activities, alongside increasing osmolyte accumulation, compared to salt-stressed plants without biostimulation. Moreover, SPE reduced reactive oxygen species (ROS) levels caused by salt stress, mitigating lipid peroxidation. The concentrations of 2% and 5% SPE applied by spraying showed the most significant results in most of the parameters analyzed. By shedding light on the underlying science behind this biostimulant effect, this research underscores the potential of SPE to enhance crop resilience and augment food production in salt-challenged environments.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

Cognitive networks have evolved to cope with uncertain environments in order to make reliable decisions. Such decision making circuits need to respond to the external world in efficient and flexible ways, and one potentially general mechanism of achieving this is grounded in critical states. Mounting evidence has shown that brains operate close to such critical boundaries consistent with self-organized criticality (SOC). Is this also taking place in small-scale living systems, such as cells? Here we explore a recent model of engineered gene networks that have been shown to exploit the feedback between order and control parameters (as defined by expression levels of two coupled genes) to achieve a SOC state. We suggest that such SOC motif could be exploited to generate adaptive behavioral patterns and might help design fast responses in synthetic cellular and multicellular organisms.

In steel structures, oblique thin steel plates serve as panel zones in structures spanning large spaces (e.g., warehouses and gymnasiums). Considerable research has been conducted on the shear buckling of panels due to seismic loads acting on a structure. Conversely, under snow or wind loads, the panel zone may experience compressive and tensile stresses simultaneously from two directions. Considering the economic preference for thin steel plates, evaluating the elastic critical local buckling stresses in the panel zone under biaxial normal stress may provide essential information to structural engineers. In this study, an elastic buckling analysis based on the energy method is performed to clarify the impact of panel geometry and boundary conditions on the elastic local buckling stresses of oblique panel zones. As confirmed, the buckling stresses derived from the energy method could simulate the local buckling stresses with accuracy comparable to that of finite element analysis, and an engineer-friendly design formula was proposed. Finally, we determined the correlation of the buckling stresses under biaxial stresses and presented a method for evaluating this correlation. Engineers can utilize the provided design equations to more efficiently and accurately calculate buckling loads, facilitating safer and more economical design of structures with oblique plates.

Bicarbonate and CO2 are essential substrates for carboxylation reactions in bacterial central metabolism. In Staphylococcus aureus, the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. A mpsABC deletion mutant can hardly grow in ambient air. In this study, we investigated the changes that occur in S. aureus when it suffers from CO2/bicarbonate deficiency. Electron microscopy revealed that mpsABC has a twofold thicker cell wall thickness compared to the parent strain. The mutant was also substantially inert to cell lysis induced by lysostaphin and the non-ionic surfactant Triton X-100. Mass spectrometry analysis of muropeptides revealed the incorporation of alanine into the pentaglycine interpeptide bridge, which explains the mutant’s lysostaphin resistance. Flow cytometry analysis of wall teichoic acid (WTA) glycosylation patterns revealed a significantly lower -glycosylated and higher ß-glycosylated WTA, explaining the mutant’s increased resistance towards Triton X-100. Comparative transcriptome analysis showed altered gene expression profiles. Autolysin-encoding genes such as sceD, a lytic transglycosylase encoding gene, were upregulated, while genes related to cell wall-anchored proteins, secreted proteins, transporters, and toxins were downregulated. Overall, we demonstrate that bicarbonate deficiency is a stress response that causes changes in cell wall composition and global gene expression resulting in increased resilience to cell wall lytic enzymes and detergents.

Recent advancements in mass spectrometry have significantly enhanced our understanding of complex lipid profiles, opening new avenues for oncological diagnostics. This review highlights the importance of lipidomics in the comprehension of certain metabolic pathways and its potential for the detection and characterization of various cancers, in particular melanoma. Through detailed case studies, we demonstrate how lipidomic analysis has led to significant breakthroughs in the identification and understanding of cancer types and its potential for detecting unique biomarkers that are instrumental in its diagnosis. Additionally, the review addresses the technical challenges and future perspectives of these methodologies, including their potential expansion and refinement for clinical applications. The discussion underscores the critical role of lipidomic profiling in advancing cancer diagnostics, proposing a new paradigm in how we approach this devastating disease, with particular emphasis on its application in comparative oncology.

Abiotic stress, especially drought stress poses a significant threat to the terrestrial plant growth, development, and productivity. Although mulberry have great genetic diversity and extensive stress tolerant traits in agroforestry systems, only a few reports offer preliminary insight into biochemical responses of mulberry leaves under drought conditions. In this study, we performed a comparative metabolomic and transcriptomic analysis on the “drooping mulberry” (Morus alba var. Pendula Dippel) under PEG-6000-simulated drought stress. Our research revealed that drought stress significantly enhanced flavonoid accumulation and up-regulated the expression of phenylpropanoid biosynthetic genes. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content were elevated. In vitro enzyme assays and fermentation tests indicated the involvement of flavonol synthase/flavanone 3-hydroxylase (XM_010098126.2) and anthocyanidin 3-O-glucosyltransferase 5 (XM_010101521.2) in the biosynthesis of flavonol aglycones and glycosides, respectively. The recombinant MaF3GT5 protein was found to recognize kaempferol, quercetin, and UDP-glucose as substrates, but not 3-/7-O-glucosylated flavonols and UDP-rhamnose. MaF3GT5 is capable of forming 3-O- and 7-O-monoglucoside, but not di-O-glucosides, form kaempferol. This implies its role as a flavonol 3, 7-O-glucosyltransferase. The findings from this study provided insights into the biosynthesis of flavonoids and could have substantial implications for the future diversified utilization of mulberry.

As technology and multimedia production have advanced, there has been a significant rise in attacks on digital media, resulting in duplicated, fraudulent, and altered data and the infringement of copyright laws. This paper presents a robust and secure digital image watermarking technique that has been implemented in the spatial domain and exploits the erratic and chaotic behaviour of the powerful elementary cellular automata rule-30. The crucial characteristics of the watermarking system, i.e., imperceptibility, capacity, and robustness, have been perfectly balanced by the suggested blind watermarking technique. In this approach, prior to embedding, the grayscale watermark image is downsized to its two Most Significant Bits (MSBs). Then, the 2-MSBs watermark is encrypted using an ECA rule-30 so as to level up the security attribute of the system. Then, the host image is scrambled using ECA rule-30 to distribute the watermark pixels throughout the host image and thus achieve the highest robustness against geometrical attacks. Finally, the encrypted watermark data is embedded into the scrambled host image using the ECA rule-30-based embedding key. The proposed method performs better in terms of imperceptibility, capacity, and robustness when compared to several systems with similar competencies. The simulation's findings demonstrate strong imperceptibility as evaluated by the Peak Signal-to-Noise Ratio (PSNR), which has an average value of 58.3735 dB and a high payload. The experimental outcomes, observed across a diverse range of standardized attack scenarios, unequivocally establish the ascendancy of the proposed algorithm over competing methodologies in the realm of image watermarking.

Saikosaponin (SS) a is a compound with various pharmacological properties and easily degraded into SSb1 and SSg in acid condition. In present work another two new degradation products of SSa formed under acid hydrolytic condition were detected and isolated by analytical and semi-preparative liquid chromatography technology, furthermore their structures were characterized as hydroxyl-saikosaponin a and SSb2 by spectral analysis, which is not only essential in stability-indicating method development and validation but also could be used as a worst case to assess the analytical method performance of SSa. Moreover their structural transformation pathways were also proposed.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation plays a crucial role as a pathogenetic mechanism in PD. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship be-tween cellular bioenergetics and YKL-40. Materials and methods: The study included 18 naïve PD and an age-matched control group (HC, n=7). Patients were diagnosed according to the MDS-PD, the UPDRS and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD’s patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. Results: New data are reported revealing changes in mito-chondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in the PD compared to HC. The protein levels of YKL-40 were three-fold higher in PD. We found a correlation between YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. Conclusion: These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD.

Alzheimer’s and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in medi-ating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

In this review we summarize the recent development in understanding the role of PIP2 in cellular function and signaling. We first discuss the effect of PIP2 on actin binding proteins addressing the mechanism of the actin cytoskeletal dynamics such as polymerization or depolymerization of the filamentous network or the coupling to membrane to generate forces. Next, we outline the role of PIP2 in membrane dynamics. We summarized how the membrane organization depends upon PIP2 in the presence of ions or transmembrane proteins that are sensitive to membrane curvature. We discuss how clathrin coated pits interact with adaptor proteins during the endocytosis process, which is facilitated by PIP2. Finally, we discuss the role of PIP2 in cell signaling and diseases.

This study examines stress distributions in adhesive joints under various loading and temperature conditions. Finite element analysis (FEA) was employed to compute the peel and shear stresses at the adhesive interface and bondline mid-section. Dependency analysis shows that mid-section peel stress significantly impacts the experimental shear strength of SLJs more than shear stress. This insight highlights the need to carefully analyze peel stress and bending moment factors. The analytical solutions proposed by Goland and Reissner were analyzed with modifications by Hart-Smith and Zhao. Hart-Smith’s approach performed more effectively, especially when the adhesive layer thickness (t_a) is 0.5 mm and the overlap length to thickness ratio (c/t_a) is ≥20. FEA revealed stress distributions at the adhesive/adherend interface and bondline mid-section. DP490 adhesive joints exhibited lower stresses than EA9696. Temperature variations significantly affected joint behavior, particularly above the adhesive’s glass transition temperature (T_g). Both EA9696 and DP490 adhesive joints displayed distinct responses to stress and temperature changes. The parabolic and biquadratic solutions for functionally graded adhesive (FGA) joints were compared. The biquadratic solution consistently yielded higher shear and peel stress values, with an increase ranging from 15% to 71% compared to the parabolic solution at various temperatures because of larger gradient of the Young's modulus distribution near the overlap ends. The ratio of peak peel stress to peak shear stress suggests selecting an adhesive with a superior peel strength or primarily reducing the peak peel stress by functionally grading is advisable, particularly if the adhesive is brittle. Comparison of stress distributions emphasize the importance of selecting adhesives based on stress type, temperature, and solution methods in optimizing adhesive bonding applications. These findings provide valuable insights for thermomechanical applications where thermal stimuli may be used for controlled debonding.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Heat stress (HS) is a strong stress factor that significantly affects the metabolism of dairy cows. The aim of the present study was to investigate how HS affects some biochemical indicators in the blood of dairy cows reared in Bulgaria. The study was conducted on a cattle farm with a capacity of 500 Holstein cows, loose housed in a free stall barn shed type. The research was carried out in three seasons - summer, autumn and winter, and a total of 77 samples were taken from the cows of the farm - 30 blood samples for each season. The cows included in the study were from 30 to 60 days in milk (DIM). Temperature and humidity data were taken from the closest to the farm weather station. Based on the conducted research, it was found that the HS reported during the summer season had a significant impact on the following blood parameters: glucose, urea, total protein and cortisol. In summer, blood glucose values were low and ranged from 1.32 to 1.63 mmol/l in cows on different lactations. Probably because of these low glucose levels, high levels of total protein, ranging from 76.92 to 86.10 g/l, were reported in cows from the first to third lactation. This protein was used by cows to provide energy from non-carbohydrate sources and as a residual product, higher blood urea levels were reported in summer, ranging from 4.79 to 5.23 mmol/l. As proof of the stressful influence of heat on the metabolism of the examined cows, the cortisol values in the summer were in the upper reference norms - 38.44 nmol/l or higher and reached 59.09 nmol/l.

The application of three-dimensional (3D) printing/bioprinting technologies and cell therapies has garnered significant attention due to their potential in the field of regenerative medicine. This paper aims to provide a comprehensive overview of 3D printing/bioprinting technology and cell therapies, highlighting their results in diverse medical applications, while also discussing the capabilities and limitations of their combined use. The synergistic combination of 3D printing and cellular therapies has been recognised as a promising and innovative approach, and it is expected that these technologies will progressively assume a crucial role in the treatment of various diseases and conditions in the foreseeable future. This review concludes with a forward-looking perspective on the future impact of these technologies, highlighting their potential to revolutionize regenerative medicine through enhanced tissue repair and organ replacement strategies.

Rhododendron chrysanthum Pall., live in Changbai Mountain being exposed to chilling temperature, high light intensities and water scarcity condition. To adapt to the harsh environment, the cold resistance mechanisms of R. chrysanthum have been successfully evolved in the long-term adaptive process. In our present work, the methods of proteomics combined with physiological and biochemical analyses were used to investigate the effects of cold stress on the photosynthesis and antioxidant system of Rhododendron chrysanthum Pall. and the molecular mechanisms involved in cold resistance of plants. A total of 153 photosynthesis related proteins were identified in present work, of which 7 proteins including Rubisco large subunit (rbcL) were up-regulated in experiment group (EG) compared with control group (CG). Simultaneously, four chlorophyll fluorescence parameters were measured in present study. The results showed that the maximum photochemical efficiency of photosystem II (Fv/Fm), actual quantum yield of PSII (Y(II)) and photochemical quenching (qP) were significantly higher in EG, whereas the non-photochemical quenching (NPQ) was notably decreased. Cold stress could lead to a significant reduction in electron transport rate (ETR) accompanied with an increase in excitation pressure (1-qP). The abundance of PetE which involved in the plants photosynthetic electron transfer was also significantly influenced by cold stress. Moreover, the up-regulated expressions and higher levels of enzymatic activities of Glutathione peroxidase (GPX) and Ascorbate peroxidases (APXs) were detected in EG. All these changes which can help plants to survive in low temperature are considered as the crucial parts of cold tolerance mechanisms. These results revealed that photosynthesis and redox adjustment play significant roles in the defense of cold-induced damage.

Purpose: Arab Americans are one of the largest ethnic groups in the United States. The mental health of Arab Americans and opinions on mental health, however, remain understudied despite higher rates of mental illness and lower rates of treatment. Unique cultural conceptualizations of mental illness may generate stigma, contributing to disparities in treatment. This study aimed to assess the attitudes and perspectives of Arab Americans regarding mental illness in order to address barriers to treatment. Methods:Using an anonymous bilingual Qualtrics survey, we assessed Arab and non-Arab participants (n = 294; ages 18+) on their conceptualizations of the causes of mental illness and on their stigma towards mental illness and mental health treatments. Comparisons were performed between Arabs and non-Arabs, as well as among Arabs. Results:Compared to non-Arabs, Arabs reported higher average mental illness stigma and were more likely to rate psychiatric medications as addictive and unhelpful. Among Arabs, being Christian, male, and older (>29 years old) were each associated with higher stigma. Arabs were less likely than non-Arabs to believe in a biological explanation for mental illness. Conclusion: Our results demonstrate higher levels of stigma towards mental illness among Arab Americans, especially Christian, male, and older Arabs, potentially related to a weaker belief in a biomedical model for mental illness. These are among the first findings describing mental illness stigma and beliefs about mental health in an Arab American community and may inform future interventions providing culturally competent care to Arab Americans.

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

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

The information about the BCoV receptors, co/receptors that might be involved in the BCoV entry to the host cells is inconceivable. In addition to that, the roles of other host cell proteases, such as Furin and TMPRSS2, have not yet been well studied during BCoV replication. The current study’s main objectives are to identify some novel BCoV receptors and host cell proteases that might fine-tune the BCoV replication, tissue tropism, and molecular pathogenesis. We used a combination of some in silico prediction, molecular docking, and gene expression profile tools to predict some new BCoV receptors out of some known other coronavirus receptors and some host cell enzymes that are potentially involved in BCoV replication. To achieve these goals, we applied the in-silico prediction tools to check the potential interactions between eh BCoV/S glycoprotein and some known coronaviruses receptors (ACE2, APN1, NPR1, CECAM-1, AXL, and DPP4). We also established some potential models for the interaction between the BCoV/S and some common host cell proteases proved to play important roles in other coronavirus replication cycle (Furin, TMPRRS2, and Cathepsin-L). To confirm our prediction models, we assessed the gene expression profiles of these potential receptors and proteases in some bovine cell lines infected with BCoV using the next generation sequencing and the qRT-PCR assay. Our results show that the NPR1, AXL1 and the ACE2 have the strongest and firm binding affinities to the BCoV-S protein. Our prediction models and gene expression profiles show the potential bindings of the Furin and TMPRSS2 to the BCoV-S polybasic cleavage site (RRSRR|A). Notably, high expression of the host cell Furin was observed in response to both BCoV/Ent and BCoV/Resp infection, whereas TMPRSS2 expression was upregulated in the case of the BCoV/Ent infection, positioning Furin as a common receptor for different BCoV isolates. Further research is needed to study the roles of these top-ranked receptors and host cell proteases in molecular pathogenesis, and tissue tropism.

Structural health monitoring has been studied by a number of researchers as well as various industries to keep up with the increasing demand for preventive maintenance routines. This work presents a novel method for reconstruct prompt, informed strain/stress responses at the hot spots of the structures based on strain measurements at remote locations. The structural responses measured from usage monitoring system at available locations are decomposed into modal responses using empirical mode decomposition. Transformation equations based on finite element modeling are derived to extrapolate the modal responses from the measured locations to critical locations where direct sensor measurements are not available. Then, two numerical examples (a two-span beam and a 19956-degree of freedom simplified airfoil) are used to demonstrate the overall reconstruction method. Finally, the present work investigates the effectiveness and accuracy of the method through a set of experiments conducted on an aluminium alloy cantilever beam commonly used in air vehicle and spacecraft. The experiments collect the vibration strain signals of the beam via optical fiber sensors. Reconstruction results are compared with theoretical solutions and a detailed error analysis is also provided.

Senescence is a stable cell cycle arrest that is either tumor suppressive or tumor promoting depending on context. Epigenetic changes such as histone methylation are known to affect both induction and suppression of senescence by altering expression of genes that regulate the cell cycle and the senescence-associated secretory phenotype. A conserved group of proteins containing a Jumonji C (JmjC) domain alter chromatin state, and therefore gene expression, by demethylating histones. Here, we will discuss what is currently known about JmjC demethylases in induction of senescence and how these enzymes suppress senescence to contribute to tumorigenesis.

Long COVID, characterized by persistent symptoms lasting from weeks to several months following initial infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), significantly impacts individuals' quality of life and poses a potential long-term burden on global healthcare systems. Clinical manifestations of Long COVID are diverse, affecting multiple systems including respiratory, cardiovascular, neurological, and gastrointestinal. While the precise mechanisms underlying Long COVID remain unclear, emerging evidence suggests involvement of various bodily pathways. This study employs bioinformatics tools to investigate the mechanisms of Long COVID and identify potential drug targets associated with key pathways, including inflammation, cytokines, immune response, coagulation, mitochondrial function, oxidative stress, and autonomic dysfunction. Tools such as the National Center for Biotechnology Information (NCBI) database, PubChem, UniProt, and iGEMDOCK were utilized for pathway analysis and molecular docking. The analysis aimed to identify drug molecules that may interact with target proteins to regulate or inhibit pathway activity, yielding several potential drug candidates for further investigation.