Introduction: The escalating morbidity, mortality, and healthcare costs associated with invasive candidiasis pose significant challenges in pediatric intensive care units (PICUs). Conventional diagnostic methods fall short in effectiveness, while various risk factors exacerbate the prevalence of these infections. This study introduces a novel model that amalgamates the Candida Score with key predictors to enhance the specificity and applicability of mortality risk assessments for pediatric patients with fungemia. Methods: This retrospective cohort study aimed to develop an integrated model for estimating mortality risk in children with fungemia in PICUs. We constructed and evaluated multiple predictive models using the Candida Score and other relevant clinical and laboratory variables. The discriminative abilities of the models were assessed using the area under the receiver operating characteristic curve (AUC). Results: The study cohort comprised 85 pediatric patients admitted between 2016 and 2020, with a median age of 6 months and a male predominance of 62.4%. The mortality rate was 45.9%. Candida albicans was the most prevalent causative agent, accounting for 37.55% of fungemia cases. Multivariable Logistic regression revealed the duration of mechanical ventilation, and the Candida Score were significant predictors of mortality. Each additional day of ventilation increased mortality odds by 11.5% (OR = 1.115, 95% CI: 1.025-1.212, p = 0.011), while a higher Candida Score more than doubled the odds (OR = 2.205, 95% CI: 1.359-3.578, p = 0.001).The Random Forest predictive model demonstrated superior discriminative performance, with an AUC of 0.838 (95% CI: 0.738-0.917), outperforming Gradient Boosting and Logistic Regression models, which had AUCs of 0.7759 (95% CI: 0.667-0.877) and 0.7085 (95% CI: 0.589-0.813), respectively. Although the internal validation yielded satisfactory results, external validation is warranted. Conclusion: This study presents an innovative approach for accurately assessing the risk of mortality due to fungemia in PICU patients by integrating the Candida Score with critical predictors. The Random Forest model emerged as the most effective predictive tool due to its exceptional discriminative ability.

Habenaria, a member of Orchidaceae family is the cosmopolitan distributions, which has significant medicinal and ornamental values. Regardless of morphology and molecular data that have been studied in recent times, the phylogenetic relationship is still under debate. Here, we sequenced, assembled, and annotated the whole chloroplast (cp) genome of two species (Habenaria aitchisonii Rchb.f. and Habenaria tibetica Schltr.ex Limpricht) of Habenaria grown on the Qinghai-Tibetan Plateau (QTP), and combined with seven already published cp genomes which may assist to uncover their genomic profiling. The two genomes ranged from 155259-155269 bp in length and both encoded 132 genes, including 86 protein, 38 tRNA and 8 rRNA. In the cp genomes, the tandem repeats (797), SSRs (2195) and diverse loci (3214) were identified. Comparative analyses of codon usage, amino frequency, microsatellite, oligo repeats and transition and transversion substitutions showed similarities among the species. Moreover, we identified 16 highly polymorphic regions with nucleotide diversity above 0.02, which may be suitable for robust authentic barcoding and inferring in the phylogeny of Habenaria species. Among the polymorphic regions, positive selection was significantly exerted on the several genes such as cemA, petA, and ycf1. This may suggest that the important adaptation stratagem for two Habenaria species on the QTP. The phylogenetic relationship displayed that H.aitchisonii and H. tibetica have closer relationship than others and the rest seven species clustered in the other three groups. Our findings also supported the idea that Habenaria could be divided into different sections. This study enriched the genomics resources of Habenaria, which may be helpful for the conservation efforts of these endangered species.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has changed considerably, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could lead not only to stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumor that finally permits liver transplantation. There are increasing reports of patients that have performed liver transplantation after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs to stimulate the immune response against tumors, they could also cause graft rejection. This review aims to evaluate the readiness and outcomes of liver transplantation in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to liver transplantation. While early evidence supports the feasibility of LT following ICI therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management.

Surface water plays a crucial role in climate change, human production, and life, making accurate monitoring and observation of surface water particularly important. However, due to the significant diversity and complexity of water distribution in surface space, accurate mapping of surface water faces considerable challenges. When extracting water bodies from medium-resolution satellite remote sensing images, CNN methods may suffer from limitations in receptive fields and insufficient context modeling capabilities, leading to the loss of water body boundary details and poor fusion of multiscale features. Currently, there is relatively little research on this issue; therefore, it is necessary to explore new combinations of deep learning networks to address these challenges. The purpose of this study is to address the above issues. We propose a new combination of deep learning networks that fully utilize multiscale information to enhance water features. Specifically, we first combine deformable convolutions with the Swin Transformer to increase effective receptive fields while better integrating global semantic information. This combination can capture features of water bodies at different scales, improve the accuracy and integrity of water extraction, and provide reliable technical support for detailed water body extraction. We tested the newly constructed model using Sentinel-2 satellite images. Our model achieved results of over 90%, with an average accuracy of 97.89%, average precision of 94.98%, average recall of 90.05%, and an average F1 score of 92.33%. In addition, our model achieved an accuracy of 98.03% in mountainous areas. Our experiments and results validate the potential of combining the Swin Transformer and deformable convolutions in detailed water body extraction.

Hydrogels have gained significant attention as vehicles for transdermal delivery systems. These polymeric-structured substances have been implemented in pharmaceutical and cosmetic applications. Many factors are employed in their preparation. Light, pH, temperature and specific molecules ligands are commonly used in the production of hydrogels. The Transdermal delivery system (TDD) is a widely used route, used to deliver actives/drugs via the skin. Hydrogels as a TDD have been shown to be efficient in enhancing the efficacy in delivering the actives and drugs. The aim of this review is to discuss the hydrogels application in both dermatological therapeutic and cosmetic applications, covering the types, and properties of hydrogel polymer networks. Furthermore, this review presents one of the most extensively used polymers (Hyaluronic acid HA) in this field and discusses the properties, preparation methods and applications of HA hydrogel patches as a delivery system, including methods of loading the actives and the releasing of these actives from them.

The deaf-mute and individuals with hearing disabilities who communicate through sign language should not be overlooked or excluded. It is a social responsibility to strive for an inclusive world without inequality. Advances in technology offer various solutions to address the communication gap, one of which is the use of computer-based sign language recognition systems. This project proposes a Malaysian Sign Language recognition model utilizing MobileNetV1, a convolutional neural network-based algorithm, to interpret sign language in real-time settings through a website application using Streamlit. The outcome of the model test shows that it has achieved a recognition rate of 96 percent. Although the proposed model has demonstrated the ability to recognize sign language, it is suggested that further improvement can be achieved by enhancing the quality and diversity of the dataset. The implementation of a more comprehensive dataset would lead to improved performance and increased accuracy of the model. This project underscores the importance of considering and accommodating the needs of the deaf-mute and individuals with hearing disabilities and highlights the potential of technology to bridge communication barriers and achieve a more inclusive society.

Immunotherapy, particularly Immune Checkpoint Blockade (ICB), has demonstrated significant efficacy in treating melanoma in recent years. However, accurately predicting treatment success and avoiding ineffective therapies remains an unresolved challenge. Therefore, this study aims to develop statistical models utilizing neural networks to forecast the effectiveness of immune checkpoint therapies for melanoma patients. Our models primarily rely on Artificial Neural Networks (ANN) to anticipate both Overall Survival (OS) and Progression-Free Survival (PFS) among melanoma patients undergoing anti-CTLA4 and anti-PD1/anti-PDL1 therapy. We incorporate gene expression data, measured in Transcripts per Million (TPM), derived from bulk tumor RNA-sequencing datasets. Additionally, clinical variables such as gender, age, and treatment type are factored into our analysis. The ANN underwent optimization to attain the highest feasible precision in anticipating the predetermined survival outcome. Issues stemming from high-dimensional data, such as overfitting, were tackled through regularization and feature selection methods. Consequently, the ANN-based model incorporating feature selection exhibited the capacity to forecast survival (PFS) in response to ICB therapy with a maximal precision of 86%. Conversely, the ANN lacking feature selection but incorporating regularization achieved accuracies of up to 72% for PFS and 71% for OS, correspondingly. In order to confront the challenge posed by limited patient samples and to assess replicability, the model underwent training and validation based on the amalgamation of all five datasets. However, this amalgamation failed to enhance predictive performance, necessitating further investigations.

The institutionalization of people with intellectual disabilities has been a common international response across cultures and generations that persists to this day. This chapter recounts its inheritance and manifestation in modern service provision. An institutional mind-set persists among clinicians and managers despite policies that emphasise the rights of persons with intellectual disability and anti-discriminatory practice. Alternative provision is rooted in person-centred practice; with a growing body of evidence for the improved quality of life that results from it. A reflective activity encourages readers to examine a recent case when they were associated with an institutional placement and what alternatives might have been sought. Yet alliances with other professionals, self-advocates and family carers will be needed to effect real and lasting changes in our service cultures and even then, the long shadows of institutional care may still persist.

Objective To investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. Design A single- center pilot trial Setting Faculty of Health, Tsukuba University of Technology, Japan Participants hypertensive community-dwelling elderly people Intervention Microcirculation was observed before and 1 min after arm-curl exercise by means microscopy of capillary with non-exercised limb. Additionally, we examined other health-related indicators. Outcome measures: Acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters.　 Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3±6.7 to 2.7±0.2 log µm/s (P

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of cancers of different origin to increase the efficacy of cytotoxic agents. Such strategy can be effective to overcome the resistance to standard chemotherapy or anti-angiogenic therapy. This review presents the results of combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells and on animal xenograft models, with a few examples of clinical trials. The effects of such approach on viability of cancer cells and tumor growth, as well as autophagy-dependent and independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ are summarized. Although the majority of experimental studies in vitro and in vivo have shown that CQ/HCQ can effectively sensitize the cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Although pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, the development of more specific compounds is required.

N-maleimide-derivatized phospholipids are often used to facilitate protein anchoring to membranes. In autophagy studies, this is applied to the covalent binding of Atg8, an autophagy protein, to a phosphatidylethanolamine (PE) in the nascent autophagosome. However, the question remains on how closely the N-maleimide PE derivative (PE-mal) mimicks the native PE in the bilayer. In the present paper, spectroscopic and calorimetric techniques have been applied to vesicles containing either PE or PE-mal (together with other phospholipids) to compare the properties of the native and derivatized forms of PE. According to differential scanning calorimetry, and to infrared spectroscopy, the presence of PE-mal did not perturb the fatty acyl chains in the bilayer. Fluorescence spectroscopy and microscopy showed that PE-mal did not alter bilayer permeability either. However, fluorescence emission polarization of Laurdan and DPH probes indicated an increased order, or decreased fluidity, in the bilayers containing PE-mal. In addition, infrared spectral data from the phospholipid phosphate region revealed a PE-mal-induced conformational change of the polar heads, accompanied by an increased hydration. Globally considered, the results suggest that PE-mal would be a reasonable substitute for PE in model membranes containing reconstituted proteins.

The inability to efficiently metabolize homocysteine (Hcy), which occurs in nutritional and genetic deficiencies, leads to hyperhomocysteinemia (HHcy) thereby causing endothelial dysfunction, a hallmark of atherosclerosis which underpins cardiovascular disease (CVD). The dysregulation of mammalian target of rapamycin (mTOR) signaling, and impaired autophagy play important roles in CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites, Hcy-thiolactone (HTL) and N-Hcy-protein (N-Hcy). However, whether these metabolites can dysregulate mTOR signaling and autophagy in endothelial cells is not known. Here, we examined the influence of HTL, N-Hcy, and Hcy on the PHF8/H4K20me1/mTOR/autophagy pathway in human umbilical vein endothelial cells (HUVEC). We found that treatments with HTL, N-Hcy, or Hcy significantly reduced PHF8 protein and mRNA expression, increased H4K20me1, and upregulated mTOR signaling. Autophagy was also impaired (significantly downregulated BECN1, ATG5, ATG7, and LC3 protein and mRNA levels). We also found that these changes were mediated by PHF8-targeting microRNA (miR): miR-22-3p and miR-1229-3p. The effects of HTL, N-Hcy, or Hcy on the miR expression and on the PHF8/H4K20me1/mTOR/autophagy pathway were abrogated by treatments with an inhibitor of miR-22 or miR-1229. Taken together, these findings show that Hcy metabolites can upregulate miR-22-3p and miR-1229-3p expression, which then dysregulate the PHF8/H4K20me1/mTOR/autophagy pathway, important for vascular homeostasis.

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology and the role of interventions to upregulate autophagy, including compounds like spermidine, resveratrol, rapamycin, and metformin. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention for spike protein related diseases; with broad implications for human health. This review presents the therapeutic possibility of using autophagy to treat spike protein related diseases, and details the interventions to deploy this therapeutic modality.

Fasting, a practice with historical roots in various cultures, has recently garnered significant interest in the field of medicine. In this article, we delve into the mechanisms underlying fasting-induced autophagy and its therapeutic applications for spike protein associated pathology. We explore the therapeutic potential of fasting on spike protein-related pathology. Additionally, we discuss factors that affect fasting, such as duration, type (dry vs. water), and the role of specific compounds like spermidine, resveratrol, rapamycin, and metformin. Furthermore, we analyse the interactions between fasting and other practices such as exercise, and highlight important considerations regarding participant characteristics, including pregnancy, breastfeeding, medication interactions, and metabolic disorders. In conclusion, fasting, coupled with an understanding of its nuances, holds promise as a therapeutic intervention with broad implications for human health.

Purpose: The intervertebral disc is a leading avascular organ in the body that may gather nutrition through diffusion. It maintains homeostasis by the use of autophagy and apoptosis to survive in unfavorable conditions such as stress and mechanical force. Therefore, excessive force and stress beyond normal conditions may cause intervertebral disc degeneration. The purpose of this study was to examine which is the better method, either external fixator (EF) or saline injection (SI), for inducing autophagy and apoptosis-mediated nucleus pulposus (NP) cell death in the discs of rat tail’s. Methods: Sixteen, nine-weeks-old male Sprague–Dawley rat tails were treated with 0.9% saline and EF (two-cross Kirschner wires) for a period ofsix and twelve weeks. Treated discs were dissected to identify the participation of autophagy and apoptosis in intervertebral disc degeneration. For identification purposes, H&E staining, Masson’s trichrome staining, and immunohistochemistry (IHC) for LC3, beclin-1, and P62 in addition to MMP-2, MMP-3, and TIMP-1 were performed. Furthermore, we performed real-time polymerase chain reaction (RT-PCR) to observe autophagy-related gene expression (beclin-1, LC3, and P62) and apoptosis-related gene expression (MMP-2, MMP-3, and TIMP-1). Results: TheEF group showed more insidious NP cell degeneration than the control (Ctrl) group. Degeneration was elevated with increasing compression duration of EF group, whereas the SI group could not distinguish the margin of annulus fibrosus (AF) and NP cells. LC3, beclin-1, and P62 showed the highest and lateral expression whilst MMP-2, MMP-3, and TIMP-1 showed up-regulated and central expression in both groups, although the SI group could not recognize the boundary between NP and AF cells. The EF group showed the highest autophagy-related gene expression whereas the SI group showed lower expression. In addition, the EF group showed more autophagy-accumulating materials than the SI group which elevated with increasing compression duration. Furthermore, the SI group induced the highest apoptotic gene expression, but the EF group showed the lowest expression. Conclusion: The EF method was better for studying autophagy and apoptosis because it enhanced intervertebral disc degeneration after compression, which is actively linked to autophagy and apoptosis. The degeneration process was elevated by increasing the compression duration, but SI could not distinguish AF and NP cell margins.

Purpose: Intervertebral disc is a leading avascular organ in the body. Hence, it may utilize autophagy and apoptosis to alive in unfavorable condition like stress and mechanical force. But excessive force and stress is a key cause to intervertebral disc degeneration (IVDD). Purpose of this study is to identify, external fixator (EF) and saline injection (SI) may induce autopahgy and apoptosis mediated nucleus pulposus (NP) cells death in rat tail’s disc and which method is better for studying autophagy and apoptosis. Methods: Sixteen 9-week-old male Sprague–Dawley rat tails were treated with 0.9% saline and EF (two-cross kirschner wires) for 6 weeks and 12 weeks as well. Treated discs were dissected for checking out participation of autopahgy and apoptosis to intervertebral disc degradation (IVDD). For identifying them, we performed H&E staining, Masson’s trichrome staining, and Immunohistochemistry (IHC) for LC3, Beclin-1and P62 as well as MMP-2, MMP-3 and TIMP-1.Furthermore, we performed quantitative polymerase chain reaction (qPCR)to check out autophagy related gene expression (beclin-1, LC3 and P62) and apoptosis related gene expression (MMP-2, MMP-3 and TIMP-1) respectively. Results: More insidious nucleus pulposus (NP) cell degeneration was indentified in (EF) group than in (Ctrl) control group. And rate of degradation was elevated with increasing duration of compression, but SI group cannot distinguish the margin of AF and NP cells. Highest along with lateral expression was found for LC3, Beclin-1, and P62 of both groups. Up-regulated and central expression was observed for MMP-2, MMP-3 and TIMP-1 of both groups, although SI group cannot recognize the margin between NP and AF cells. Utmost autophagy related gene expression was identified in EF group than in SI group. Besides, maximum autophagy accumulating materials was found in EF group than in SI group. And it was amplified along with increasing the duration of compression. Highest, apoptotic gene expression was observed in SI group, whereas, EF group showed lowest expression. Conclusion: External fixator (EF) method was better to study autophagy and apoptosis because it enhanced IVDD after compression which is actively linked with autophagy and apoptosis. Degeneration process was conversely proportional along with duration of compression. On contrary, saline injection (SI) could not distinguish AF and NP cell border.

With a highly efficient optical absorption capability, bismuth selenide (Bi2Se3) nanomaterial can be used as an outstanding photothermal agent for anti-tumor treatment and shows promise in the field of nanotechnology-based biomedicine. However, little research has been done on the relevant mechanism underlying the photothermal killing effect of Bi2Se3 nanomaterial. Herein, the photothermal effects of Bi2Se3 nanoparticles on A549 cells were explored with emphasis put on autophagy. Firstly, we characterized the structure and physicochemical property of the synthesized Bi2Se3 and confirmed their excellent photothermal conversion efficiency (35.72%), photostability, biocompatibility and ability of photothermal killing on A549 cells. Enhanced autophagy was detected in Bi2Se3-exposed cells under an 808 nm laser. Consistently, an elevated expression ratio of LC3-II to LC3-I, a marker of autophagy occurrence, was induced in Bi2Se3-exposed cells upon NIR irradiation. Meanwhile, the expression of cleaved-PARP was increased in the irradiated cells dependently on the exposure concentrations of Bi2Se3 nanoparticles. Pharmacological inhibition of autophagy by 3-methyladenine (3-MA) further strengthened the photothermal killing effect of Bi2Se3. Meanwhile, stress-related signaling pathways including p38 and SAPK/JNK were activated coupled with the attenuated PI3K/Akt signaling. Our study figures out that autophagy and the activation of stress-related signaling pathways were involved in the photothermal killing of cancerous cells by Bi2Se3, which provides a more understanding of photothermal nanomaterials.

Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people around the world. Neuronal death in AD is initiated by the toxic action of oligomeric amyloid-β (Aβ) peptides. The formation of membrane channels by Aβ is a primary molecular action and does not require any other proteins. Channels are formed by short amyloid fragments faster and more frequently than by full-length peptides. The channel formation is dependent on an electrostatic interaction between a positively charged peptide and a negatively charged membrane. Negative membranes can be found in several locations of a cell – the inner leaflet of plasma membrane, mitochondria, and lysosomes, which all are well-known cellular targets in AD. Considering that the amyloid enters a cell by endocytosis and is exposed to lysosomal enzymes, we propose the amyloid degradation toxicity hypothesis. Endopeptidases degrade the endocytosed peptide. Produced fragments form membrane channels, which can transfer various ions (including protons) and even relatively large compounds. The neutralization of lysosomal content inactivates enzymes, which fails the whole system of recycling cellular content, including autophagy. The permeabilization of lysosomes could also lead to cell death through necrotic and apoptotic mechanisms. We discuss several mechanisms that describe how amyloid degradation products reach plasma and mitochondrial membranes, and form membrane channels. The pathogenesis of AD is discussed at various levels in a context of how the primary molecular mechanism of membrane channel formation could progress into the disease state. The discussion starts at the molecular level and extends to why the development of a disease takes years and is closely associated with aging. The proposed hypothesis offers an interpretation to several clinical observations such as the involvement of iron metabolism and an inverse association between developing Alzheimer's disease and cancer. Predictions about potential biomarkers and effectiveness of future treatments are discussed.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. In this study, the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in liver were investigated. Rats were fed the diets with (0.54 %) or without EGCG supplementation for four weeks and were then intraperitoneally injected with acetaminophen (1g/kg). Results showed EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by increasing the Bax/Bcl2 ratio in liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen-glutathione and acetaminophen-protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in liver after acetaminophen treatment. Our results indicate that EGCG may lower oxidative stress and reduce the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in liver and thus lower hepatotoxicity

Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, and immune cells (T, B, macrophages, and TNF-alpha levels, immunohistochemistry) and tumor growth, oxidative stress, apoptosis, autophagy, and sirtuin-1 markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N=9/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, and sirtuin-1 marker increased. Conclusion: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and sirtuin-1 levels, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.

Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern, but it can be mitigated by employing different combination therapies. Resveratrol is a polyphenolic compound annex the outpouring of p53 and its pro-apoptotic modulator PUMA. Here, we showed the p53-independent activation of apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB activation that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in Non-Small Cell lung adenocarcinoma cells (NSCLC), resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells via a co-treatment of resveratrol and TRAIL, which was assessed by the loss of mitochondrial membrane potential, resulting in the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis of lung cancer cells. Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the eminent therapeutic strategy to treat lung cancer.

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

Limited research has been conducted on the metabolites present in the essential oils (EOs) of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (PR, syn. Lamiophlomis rotata (Benth.) Kudô), and their potential pharmacological activities, such as antioxidant properties, are often overlooked. We conducted a metabolomics-based screening to identify the characteristic metabolites (CMs) in the EOs extracted from PR. Meanwhile, we evaluated their in vitro antioxidant activities (AOAs). The EOs obtained through hydro-distillation are characterized by a light yellow color and a fresh, elegant fragrance. Cryoprecipitation was used to separate the crystals (Crs) from the EOs, resulting in the crystal-free EOs (CFs). A total of 121 components are identified and quantified in the EOs, Crs, and CFs. Among them, 84 were reported for the first time from such EOs. The major compounds include long-chain fatty acids (LCFAs) and their esters, such as palmitic acid (PA), myristic acid (MA), linoleic acid (LA), oleic acid (OA), stearic acid, and methyl palmitate (MP). Furthermore, 11 kinds of apocarotenoids (also called norisoprenoids) were first systematically investigated. Among them, eight C13-norisoprenoids, with trans-β-damascenone (DN) being particularly notable for its flavor, were identified. A sum of 11 CMs are screened , including PA, MA, LA, OA, MP, hexahydrofarnesyl acetone, phytol (PT), DN, stearic acid, linalool, and hexanal. These CMs are biosynthesized through FAs and 2-C-Methyl-D-erythritol 4-phosphate/1-Deoxy-D-xylulose 5-phosphate pathways. The in vitro AOAs of EOs, Crs, CFs, and seven selected CMs (PA, MA, LA, OA, MP, PT, and DN) were evaluated. Generally, PA and MA exhibited pro-oxidant activities (POAs) or weak AOAs. LA and OA demonstrated POAs or weak AOAs at lower concentrations, but at higher concentrations, they displayed medium to strong AOAs. Importantly, the CFs typically exhibited stronger AOAs compared to the corresponding EOs and Crs, potentially due to variations in their PA content. Overall, this study provides valuable insights into the potential utilization of EOs from PR.

This study used a completely randomized design with a bifactorial arrangement in triplicate to evaluate dif-ferent concentrations of flavonoid extracts from orange (Citrus sinensis), onion (Allium cepa), tamarillo (So-lanum betaceum) and cocoa (Theobroma cacao) peels in combination with the yeast Saccharomyces cerevisiae to inhibit the growth of Listeria monocytogenes in fruit juices. The shells were dehydrated at 50-57 °C for 8 hours and pulverized. The dehydration yields were: orange (32 %), onion (13 %), tamarillo (14 %) and cocoa (34 %). Flavonoids were extracted with Soxhlet using 70% ethanol for 5 hours, concentrating with a rotary evaporator. They were quantified by UV spectrophotometry and the Folin-Ciocalteu method, being the highest in orange (300,75-372,60 mg Q/L) and onion (205,70-534,96 mg Q/L), while tamarillo presented the lowest, with possible errors in the measurement. Soluble solids losses ranged from 2,30 g (cocoa) to 5,27 g (orange). Cocoa and orange extracts showed greater potential as natural preservatives, inhibiting the growth of Listeria monocytogenes in fruit juices, with a minimum inhibitory concentration of 300 µg/mL and 400 µg/mL, re-spectively.

Fluorinated cytokinins have emerged as promising alternatives to traditional cytokinins in plant tissue culture, offering enhanced stability and bioactivity. However, their metabolic fate and impact on endogenous cytokinin profiles remain largely unexplored. This study investigated the cytokinin metabolism of Phalaenopsis orchids under varying exogenous cytokinin treatments (BA, FmT, FmTR) and culture conditions (open vs. closed containers). The results reveal distinct metabolic profiles associated with each treatment, highlighting the complex interplay between exogenous and endogenous cytokinin levels. Additionally, we proposed an alternative inactivation pathway involving the conversion of FmTR and BA to pT and pTR. These findings provide valuable insights into the intricate relationship between cytokinin metabolism and plant growth under in vitro conditions, with implications for optimizing micropropagation protocols

The increasing focus on sustainability and the adoption of green practices across industries underscore the necessity of equipping future professionals with competencies in implementing sustainable solutions. This study explores the perceptions of former students from two departments within the technological sector towards sustainability practices. A cross-sectional online survey was carried out among alumni from two programs at the University of Thessaly, a university recognized for its commitment to sustainability and green initiatives as a member of the INVEST European University alliance. The survey questionnaire included background inquiries and 16 statements designed to gauge alumni perspectives towards sustainability practices. Specifically, it aims to assess their views through self-assessment and compare differences between the two alumni groups. Responses were collected on a 5-point Likert scale ranging from strongly disagree to strongly agree. A total of 300 graduates from the Computer Science and Telecommunications as well as Electrical Engineering undergraduate programs were encouraged to take part in the survey, achieving a response rate of 69%. Of those who responded, 61% (n = 126) represented the Computer Science and Telecommunications group, while 39% (n = 81) were from the Electrical Engineering program. Our findings indicate a generally positive attitude towards sustainability, with statistically significant differences in perspectives on the implementation of sustainable technologies and stakeholder engagement. These results underscore the necessity of integrating sustainability education deeply within the curricula of technological programs to cultivate a workforce capable of addressing future environmental challenges. This study illuminates the critical role of educational frameworks in shaping the sustainability competencies of technology professionals.

Introduction: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, character-ized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). Purpose: This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p=0.001 and p=0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p3gr/24h with diffuse fusion of podocyte foot processes (p=0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine represent markers of podocyte dysfunction and in our study they were associated both with serum creatinine and histological chronicity indices.

The rise of the Internet has enabled people to express their opinions on various subjects through social media, blogs, and website comments. As a result, there has been a significant increase in research on sentiment analysis. However, most of the research efforts have focused on analyzing sentiment in English-language data, neglecting the wealth of information available in other languages. In this paper, we provide a comprehensive review of the current state-of-the-art in multilingual sentiment analysis. The survey investigates techniques for data preprocessing, representation learning, and feature extraction in multilingual sentiment analysis. It explores cross-lingual transfer learning, domain adaptation, and data augmentation methods that enhance the performance of sentiment analysis models, particularly in low-resource languages and domains. It provides insights into the state-of-the-art approaches, challenges, and opportunities in this evolving field and encourages further advancements in multilingual sentiment analysis research.

The paper presents the observational, remote sensing and model simulation to analyze Southern Brazil Antarctic Ozone Hole influence (SBAOHI) events occurred between 2005 and 2014. To an-alyze it we use Total Ozone Column (TOC) data provide by Brewer Spectrophotometer (BS) and OMI (Ozone Monitoring Instrument) instrument satellite, besides the AURA/MLS (Microwave Limb Sounder) instrument satellite ozone profiles was utilized with DYBAL (Dynamical Barrier Localization) code in MIMOSA (Modélisation Isentrope du transport Mésoéchelle de l’Ozone Stratosphérique par Advection) model Potential Vorticity (PV) fields. TOC has 7.0 ± 2.9 DU re-ductions average in 62 events. October have more events (30.7%). Polar Tongue events are 19.3% of total, being in October more frequently observed (50% of cases), with medium intensity (58.2%) and in stratosphere medium levels (55.0%). Already Polar Filament events (80.7%) are more frequent in September (32.0%), medium intensity (42.0%) and in stratosphere medium lev-els (40.7%). ENSO index positive phase influenced 61.3% of events, having dominance in all in-tensity categories (minor 57.9%, medium 51.6%, major 58.3%), while the equilibrium dominate the QBO influence with 50% of total cases in positive phase and 50 % in negative phase.

UVA1 phototherapy has been reported to mediate some of its effects via FICZ/AHR/MAPK signaling. A proof-of-concept study was performed to assess whether a topical solution of L tryptophan formulated to favor the generation 6-formylindolo[3,2-b] carbazole (FICZ) demonstrated activity at the aryl hydrocarbon receptor (AHR) as assessed by the intensity of cytochrome P450 1A2 staining. Ten participants applied a trial agent consisting of L- tryptophan, lecithin, polyvinyl alcohol and ethanol followed by 36 sessions of graduated sun exposure increasing to a total of 20 Joules per square centimetre. At the end of the trial, biopsies were taken from a treated site with photo-protected buttock skin used as a control. Assessment was via intensity of cytochrome P450 1A2 staining. An average baseline value of 53488923 units was obtained at the control site and 972214294 at the treatment site supporting the concept that this preparation displays activity at the AHR. As the components of this preparation are known to have UV absorbing properties and are potentially permissive of UVA-1 transmission, UV absorbance was assessed for natural sunlight and at 365 and 395nm confirming strong absorption in the UVB and UVA-2 spectra with partial transmission in the UVA-1 spectrum.

In diabetic foot injury prevention, no studies relate physical activity with the inflammatory response of the plantar tissues, evaluated by thermography and pressure distribution. These measurements are easy to be implemented in diabetic foot follow-up. The objective of this study was to analyze whether the plantar skin response, evaluated with thermography, after physical activity in healthy or diabetic patients, is a foot ulcer prognostic tool and to asses if there is a correlation between exercise intensity, plantar pressure and plantar thermographic response. A systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format in the PubMed, Scopus and Web of Science databases, with no year limit during the second quarter of 2024. A total of 14 studies have been included in this review. The use of infrared thermography for early inflammatory tissue detection, plantar pressures and the monitoring of controlled physical activity, make possible to monitor changes that allow the identification of patients at risk of developing foot ulcers.

A major problem of the technological production process of the metallurgical-grade silicon is formation of a large amount of microsilica. However, this material can be a significant source of raw materials for its own production. Hence, this study is aimed to solve the problem of micro-silica utilization, i.e. the technogenic dust-like waste generated during the melting of the technical-grade silicon. Within this study, the technology of the joint briquetting of microsilica was investigated with the carbonaceous reducing agents, i.e. by obtaining of mono-charge and by melting of the technical-grade silicon from the obtained mono-charge in the 200kVA ore-thermal furnace. Results of the study show that the briquettes in the melting process of the technical-grade silicon can be used in the range from 0 to 50%. The using of briquettes may significantly improve the technological parameters. When briquetted charge is applied only, the technological parameters will deteriorate significantly. The material balance of silicon melting showed the recovery rates of the main elements (Si, Al, Ca and Fe). It recorded a decrease in content of aluminum from 1.9-2.1% to 0.5-0.7%, calcium from 0.2-0.3% to 0.07-0.1% and titanium from 0.2-0.23% to 0.11-0.13% during the transition to briquetted monocharge. Phosphorus content increased from 0.004-0.005 to 0.011-0.013%.

Treating central giant cell granuloma (CGCG) is challenging due to high recurrence rates and variable therapy responses. This study examines the efficacy of various treatments in reducing CGCG recurrence. A literature review explored outcomes of surgical excision, curettage, intralesional corticosteroid injection, and adjuvant therapy, considering factors like lesion location, size, and histological features. Aggressive surgical techniques such as en bloc resection were found to potentially lower recurrence rates compared to conservative approaches. However, treatment should be tailored to individual patient needs. Further research is needed to confirm these findings and improve treatment strategies. A concise literature review was conducted using PubMed, MEDLINE, and Google Scholar, focusing on papers published from 1986 to 2024. Search terms included "central giant cell granuloma," "recurrence," "treatment modalities," and "surgical excision". Studies reporting recurrence rates and treatment outcomes for CGCG were analyzed. Twenty-nine studies were reviewed, including six studies on surgical excision and curettage, eight studies on intralesional corticosteroid injections, six studies on calcitonin therapy, five studies on interferon alpha therapy and four studies on the therapy with denosumab. Analysis indicated that aggressive surgical treatments like en bloc resection were associated with lower recurrence rates compared to conservative methods. Predictors of recurrence included lesion size (>3 cm), location (mandible), and aggressive histopathological features. Aggressive surgical excision combined with nonsurgical methods may lower recurrence rates, while conservative techniques remain viable in some cases. Further prospective research is needed to validate these findings and enhance CGCG treatment options.

The clothing industry is a hotbed for exploitative working conditions and environmental damages, of which affluent global North countries remain a substantial driver. The circular economy is a potential solution to these issues, but its social implications remain unclear. Using the UK as a case study, this article analyses the global social impacts of a transition to circular clothing economies in the global North, finding these to be (almost) entirely dependent upon the intentions and design of the associated politics. Some aspects of a transition will be unambiguously good for some people; others will only be beneficial with careful governance. Moreover, entrenched global economic inequalities leave trade-offs borne largely by the global South, highlighting the need for circular economy research – its drive for localisation notwithstanding – to look globally to consider how a fair transition can be achieved.

This research aims to explore the adoption and impact of green supply chain practices (GSCP) on sustainable development in Bangladesh. The study seeks to understand the current state of GSCP adoption across various industries, identify key drivers and barriers, assess the perceived benefits and challenges, and evaluate the overall impact on environmental sustainability, economic performance, and social well-being. The research employs a qualitative approach, utilizing interviews with key stakeholders, document analysis, and literature review to gather data and insights. Interviews were conducted with representatives from government agencies, businesses, civil society organizations, and academia to obtain diverse perspectives on GSCP adoption and its implications for sustainable development in Bangladesh. The findings reveal a mixed scenario of GSCP adoption across different industries in Bangladesh, with sectors such as textiles leading the way. Key drivers of GSCP adoption include regulatory pressures, market forces, corporate social responsibility initiatives, and financial incentives. However, organizations face significant barriers such as high upfront costs, lack of awareness and expertise, regulatory uncertainty, and supply chain complexity. Despite these challenges, GSCP offer various benefits, including environmental sustainability, economic performance, and social well-being. Successful initiatives demonstrate tangible impacts, highlighting the potential of GSCP to contribute to sustainable development. The research is limited by its qualitative nature and focus on selected industries and stakeholders. Future studies could employ quantitative methods and broader sampling to provide a more comprehensive understanding of GSCP adoption and its implications in Bangladesh. The findings provide actionable insights for policymakers, industry leaders, and other stakeholders to promote GSCP adoption and enhance sustainable development in Bangladesh. Strategies for overcoming barriers and maximizing benefits are outlined, emphasizing the importance of collaboration and capacity-building initiatives. GSCP adoption can have positive social implications by promoting ethical labor practices, improving working conditions, and fostering community engagement. By prioritizing sustainability, businesses can contribute to social well-being and inclusive growth. This research contributes to the literature on GSCP adoption and sustainable development in Bangladesh by providing empirical insights and practical recommendations. The study adds to the understanding of the drivers, barriers, benefits, and challenges associated with GSCP adoption, highlighting the importance of integrating environmental, economic, and social considerations in supply chain management.

The Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical composition. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with concentrations of EOs. Repellent rates ranged from 80.50% to 100.00% after treating D. citri for 6 hours with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 hours of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24-hour repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47-93.15 mL/L, and for adults, it was 60.72-111.00 mL/L. These results show that when PG is used as the reference material, both ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

The purpose of this research is to examine the benefits and limitations of implementation of novel digital academic advising systems using automated collection and reporting processes for ABET student outcomes data based on principles of authentic OBE for effective developmental advising. We examine digital developmental advising models of undergraduate engineering programs in two universities that employ customized features of the web-based software EvalTools® - Advising Module based on assessment methodology incorporating the Faculty Course Assessment Report, Performance Indicators and hybrid rubrics classified according to the affective, cognitive and psychomotor domains of Bloom’s learning model. A case study approach over a six-year period is adopted for this research. The two case studies present results of samples of developmental advising activity employing sequential explanatory mixed methods models using a combination of quantitative and qualitative analyses of a) detailed students’ outcomes and Performance Indicators information; and b) self-evaluation of their professional development and lifelong learning skills. The findings of this study show that digital advising systems employing the Faculty Course Assessment Report using Performance Indicators and hybrid rubrics can provide comprehensive and realistic outcomes data to help both developmental advisors and students easily identify the specific cause of performance failures, implement practical recommendations for remedial actions and track improvements. Inherent strong skills can also be identified in academically weak students by observing patterns or trends of relatively better performing outcomes to reinforce natural affinity for learning specialized competencies and pursue related and successful career paths.

Medical image segmentation is a critical step in various healthcare applications, aiding in diagnosis, treatment planning, and disease monitoring. In this study, we investigate the efficacy of a segmentation approach based on the 2D wavelet transform. Leveraging a dataset comprising 10 diverse medical images, we evaluate the performance of our segmentation method using three key metrics: accuracy, precision, and recall. Our findings demonstrate that the proposed approach enhances segmentation accuracy, offering promising results compared to existing methods. By harnessing the multi-resolution feature extraction capabilities of the 2D wavelet transform, our method achieves improved delineation of medical image structures, paving the way for more accurate and efficient healthcare interventions.

This study presents a groundbreaking approach in the field of gaming AI, focusing on the classic game” Pacman” through the lens of DRL integrated with advanced optimization techniques. The core of the research involves adapting DRL models for” Pacman”, utilizing the ESO for hyper- parameter tuning. These novel adaptations significantly enhance the AI agent’s performance, demonstrating a remarkable improvement in adaptability, responsiveness, and efficiency within the game environment. A pivotal aspect of this research is the innovative integration of metaheuristic optimization techniques into the DRL framework, a first in the domain of Atari gaming AI. This integration has proven essential in fine-tuning the DRL models, leading to a more effective and dynamic gaming experience. The study thoroughly evaluates and compares the performance of these algorithms, providing empirical support for their effectiveness and setting a new benchmark in AI-driven game development. The implications of this research extend beyond gaming AI, opening up possibilities for future exploration in several directions. Expanding DRL models to other complex gaming environments, continuous algorithmic enhancements, real-time learning adaptations, and applying these principles to robotics and autonomous vehicles are examples. The research also emphasizes ethical and responsible AI use in gaming to address fairness and addiction issues.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

Verification of inclusivity of molecular detection methods gives indications on the reliability of viral infections diagnosis because of the tendency of viral pathogens to undergo sequence variation. This study was aimed to select inclusive probe based reverse transcription quantitative PCR (RT-qPCR) assays for the diagnosis of the most widespread and detrimental viruses infecting honeybees, namely the acute bee paralysis virus (ABPV), the black queen cell virus (BQCV), the chronic paralysis bee virus (CBPV), the deformed wing virus variants A (DWVA) and B (DWVB), and the sacbrood virus (SBV). Therefore, detection methods previously described were re-evaluated in silico for specificity and inclusivity. Based on this evaluation, selected methods were modified or new ones were designed and tested in duplex RT-qPCR reactions. The limits of detection (LODs), effect of multiplexing on sensitivity and viral RNA quantification potential in bees and hive debris were assessed. This study made available diagnostic assays able to detect an increased number of virus variants compared to previously described tests and two viral pathogens in a single PCR reaction.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Coal bottom ash (CBA) is a byproduct of coal-burning power plants. This material can be used as a fine aggregate replacement in concrete to reduce global natural material depletion. Concrete usage is increasing rapidly; subsequently, the industry’s carbon footprint is increasing. Using CBA in the construction industry will reduce the technical and economic problems associated with power plants by reducing solid waste. This project aimed to determine if adding new sustainable materials, such as CBA, to concrete will reduce natural raw material usage, energy consumption, and greenhouse gas emissions while improving performance. This study included two projects: comparing increased CBA content to the two-control project and determining the optimum content based on the compressive strength. The optimum CBA content is 50%, which reduces fine aggregate usage in a concrete mix by 50% while maintaining equivalent or better concrete strength than a pure Portland concrete mix without CBA. The air content of the concrete mix containing % CBA decreased with increased CBA content and compressive strength, possibly due to the spacing factor of the voids in the mix and CBA’s porous and fineness behavior. The CBA optimum content had a unit weight lower than the controls for both projects, which makes the CBA mix a lightweight concrete. Using this material can significantly reduce natural material usage and environmental harm by reducing CBA waste disposal and improving concrete performance.

To facilitate the promotion and application of the whole process engineering consulting (WPEC) model, the transmission mechanism of influencing factors in WPEC's promotion and application is investigated. It identifies and categorizes the influencing factors within the framework of "external environment-project factors-stakeholders", systematically organizing and summarizing ten primary categories and thirty-eight secondary influencing factors of WPEC's promotion and ap-plication. Utilizing the complex network analysis method, a network of influencing factors in the promotion and application of WPEC is constructed. The network is then converted into three binary networks based on weight, which are subjected to structural analysis and motif analysis. On this basis, the transmission mechanism of influencing factors in WPEC's promotion and applica-tion and its causations are explored.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

Physical exercise is the greatest stress on the cardiovascular system, not only in humans but also in all vertebrates. Consequently, the cardiovascular response cannot be thought of as having only one "anthropocentric" interpretation. The modulation of cardiac output (Q) in response to exercise in the five major groups of vertebrates exhibits considerable variability. Moreover, the response of the heart rate (HR) and the stroke volume (SV), the fundamental factors that cause the rise in Q, is also highly variable. The difference in the range of HR is difficult to determine in many vertebrates, both at rest and at maximal effort. Additionally, the increase in SV varies among vertebrates. For example, while rainbow trout and leopards increase their SV by increasing end diastolic volume (EDV), humans do so at the expense of both increasing EDV and reducing end systolic volume (ESV). The variation in arterial pressure that arises during exercise varies notably among vertebrates, such as amphibians, whose blood pressure values do not increase as significantly as in mammals. Such differences in cardiovascular response among vertebrates may be linked to their habitat or living environment. This review aims to analyze the cardiovascular response of vertebrates to physical exercise as the most common stressor.

HIV incidence remains alarmingly high among female sex workers (FSWs) in low- and middle-income countries, with Uganda being no exception. The elevated risk of HIV transmission among this vulnerable population can be attributed to a complex interplay of factors, including engaging in sexual activities with multiple partners, inconsistent condom usage, substance use, and structural barriers, such as legal criminalization and pervasive stigmatization by healthcare providers. To combat this epidemic, various HIV prevention interventions have been devised, targeting these multi-faceted challenges. This study involved conducting focus groups among FSWs and healthcare providers in Uganda, with the overarching objective of informing the development of a tailored HIV prevention intervention aimed squarely at FSWs. Through these discussions, valuable insights were gained into FSWs’ perceptions of their HIV risk, their attitudes regarding HIV prevention strategies, and their recommendations regarding the content and delivery of future interventions.

Gram-negative bacterial infections pose a significant threat to public health. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and induces innate immune responses, autophagy and cell death, which have major impacts on the body physiological homeostasis. However, the role of TLR4 in bacterial LPS-induced autophagy and apoptosis in large mammals remains unknown, which are closer to humans than rodents in many physiological characteristics. So far, few reports focus on the relationship between TLR, autophagy and apoptosis in large mammal levels. We urgently need more tools to further explore their crosstalk. Here, we generated a TLR4-enriched mammal model (sheep) and found that a high-dose LPS treatment blocked autophagic degradation and caused strong innate immune responses and severe apoptosis in PBMCs of transgenic offspring. Excessive accumulation of autophagosomes/autolysosomes might contribute to LPS-induced apoptosis in PBMCs of transgenic animals. Further study demonstrated that inhibiting TLR4 downstream NF-κB or p38 MAPK signaling pathways reversed the LPS-induced autophagy activity and apoptosis. These results indicate that the elevated TLR4 aggravates LPS-induced PBMCs apoptosis by leading to lysosomal dysfunction and impaired autophagic flux, which is associated with TLR4 downstream NF-κB and MAPK signaling pathways. This study provides a novel TLR4-enriched mammal model to study its potential effects on autophagy activity, inflammation, oxidative stress and cell death. These findings also enriched the biological functions of TLR4 and provided powerful evidence for bacterial infection.

Objective: The purpose of this study was to investigate the effect of aerobic exercise on myocardial injury induced by I/ R in rats by regulating SIRT3/SOD2/NF-κB signaling pathway, and to provide theoretical guidance for clinical treatment of myocardial I/R injury.Methods:SPF Male Sprague-Dawley(SD) rats were randomly assigned to 4 groups: Sham operation group(n=10), I/R group(n=10), Aerobic exercise group(n=10)and Aerobic exercise+κ-receptor antagonist group(Pro DTC group，n=10). The left anterior descending coronary artery(LAD) of rats was ligated and re-canalized to establish I/R rat model. Hematoxylin-eosin(HE) staining was performed to examine histological morphology in myocardial tissues of each group. The biological analysis was performed to measure cTnI、CK-MB、BNP levels in blood samples of each group. The expression levels of SOD2, TLR4, and p65 in myocardial tissues were measured by immunohistochemical assay. The influence of aerobic exercise on Beclin-1 、LC3II/I、SIRT3, TLR4, and phosphorylated p65 was measured by Western blotting.Results: The result of histological morphology examination revealed that Aerobic exercise group exhibited integrated cardiac myofilament, less inflammatory cell infiltration, as much as significantly decreased cellular edema. Measurement of cTnI、CK-MB、BNP revealed that oxycodone post-treatment reduces the injury of myocardial tissues(P<0.05). Immunohistochemical staining results revealed that aerobic exercise clearly decreased the expression of TLR4 and p65, and increased the expression of SOD2(P<0.05). Besides, Western blotting revealed that aerobic exercise down-regulated the expression of Beclin-1 、LC3II/I、TLR4 and phosphorylated p65, up-regulated the expression of SIRT3(P<0.05).Conclusions: Aerobic exercise significantly improved myocardial I/R injury. The mechanisms may be associated with activating κ-receptor to regulate SIRT3/SOD2/NF-κB pathway.

Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The Ubiquitin-Proteasome System (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the ER and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination have remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for the basal function of mitochondria, metabolic implications, and possible therapeutic applications.

Autophagy refers to the degradation of cytoplasmic constituents by a lysosomal-mediated pathway, which plays a critical role in maintaining cellular homeostasis. Importantly, dysregulation of autophagy has been implicated in multiple neurodegenerative disorders. Previous studies reported that autophagy affects the processing of amyloid precursor protein (APP), thus stimulating β‐amyloid (Aβ) production in Alzheimer’s disease (AD) eventually. Although the mechanism of autophagy modulation on APP processing and its pathogenesis has not yet been fully elucidated at the molecular level, but modulation of autophagy has received considerable attention as a promising approach for the treatment of AD. In the early stage of AD, Aβ may prompt autophagy to facilitate its removal via mTOR‐independent as well as-dependent pathways. However, a recent study proposed that autophagy processes are not properly regulated as AD continues to progress, and consequently, the production of Aβ tends to accumulate rapidly. Meanwhile, a number of autophagy-related genes (Atg) as well as APP genes are also thought to influence the development of AD, which may serve as a bi‐directional link to autophagy and AD pathology. In this review, we summarized current observations related to autophagy regulation and APP processing, focusing on their dynamic modifications associated with the progression of AD. Recent findings together highlight the essential role of autophagy in the removal and clearance of APP and Aβ deposition in the pathological condition of AD.

Curcumin is one of the bioactive metabolites of turmeric (Curcuma longa), known for its pleiotropic pharmacological actions, including antioxidant and anti-inflammation, anticholinesterase, immunomodulation, and neuroprotection. Substantial evidence suggests the therapeutic benefits of curcumin against neurodegenerative disorders, including Alzheimer’s disease (AD), acting on a diverse array of brain targets that make the molecular mechanisms complicated. System biology level-investigation could potentially present a comprehensive molecular mechanism to delineate the neuropharmacological action of curcumin. In this study, we used integrated system pharmacology and molecular simulation analysis to gain insights into the underlying mechanism of curcumin action against AD. Network pharmacology study identified curcumin-targeted potential cellular pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, neurotrophin signaling, toll-like receptor (TLR) signaling, and autophagy, and proteins such as tropomyosin receptor kinase B (TrkB), liver X-receptor-beta (LXR-β), estrogen receptor-β (ER-β), mammalian target of rapamycin (mTOR), TLR-2, N-methyl-D-acetate receptor subunit 2B (GluN2B), β-secretase and glycogen synthase kinase-3β (GSK-3β), which are intimately associated with neuronal growth and survival, immune response, and inflammation. Moreover, the molecular modeling further verified that curcumin showed a significant binding affinity to mTOR, TrkB, LXR-β, TLR-2, ER-β, GluN2B, β-secretase, and GSK-3β, which are the crucial regulators of molecular and cellular processes associated with AD. Together, the present system pharmacology and in silico findings demonstrate that curcumin might play a significant role in modulating AD-pathobiology, supporting its therapeutic application for the prevention and treatment of AD.

Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was detected also for other microtubule and microfilament factors, namely MAP2S1801, MARK1S394, MAP1AT1794, KIF1AS1537, 4.1NS541, 4.1GS86 and ADD2S528. While the MAP1B heavy chain supports regeneration and growth cones, its light-chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2S299, VPS13DS2429 and VPS13CS2480 in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in D. melanogaster that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, ANK2 gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). ω3-Polyunsaturated fatty acids (ω3-PUFAs) show protective effects against various renal injuries. It was recently reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI. Renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of LC3, Beclin-1, and Atg7; lower amounts of p62; and higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

We evaluated the mono- and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

According to evolutionary cancer cell biology ECCB, cancer stem cells do not arise from normal stem cells, but rather from the functional ACD phenotype of the germline. This phenotype proliferates through asymmetric cell division, producing self-renewing cells and non-proliferating daughter cells with cancer stem cell qualities (CSCs). ECCB posits that cancer stem cells themselves do not proliferate. Similar to protists, there is a close reciprocal relationship between both sister cells that collectively form a germ and stem cell lineage. These sister cells share functional roles: the proliferating cancer germline cells generate stem cells, while the non-proliferating cancer stem cells accumulate progenitor cells for new germline clones. ECCB distinguishes between primary CSCs, which are associated with carcinogenesis and primary tumors, and secondary CSCs, which are linked to metastases. This unicellular stem cell system is homologous to that of parasitic protists, such as amoebae. Both cancer stem cells and amoebae stem cells are generated by an oxygen-sensitive germline and are vulnerable to damage when oxygen levels exceed 6.0% (germline hyperoxia). Oxygen concentrations above this threshold can damage the germline genome. Dysfunctional germline cells do not undergo senescence; instead, they continue to cycle through defective symmetric cell cycles However, to regain functionality, the germline genome requires repair by hyperpolyploid giant cells known as native PGCCs, which are homologous to the multinucleated genome repair structures MGRS found in protists. Native PGCCs differ in some respects from genotoxic-induced PGCCs

Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In the current study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nano-hydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrusion-based printing. Rheological tests perfomed on crosslinked hydrogels confirm the formation of solid-like structures consistently indicating a higher storage modulus compared to the loss modulus. The swelling behaviour analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlueTM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favoured a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2), in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro.

This study fabricated piezoelectric fibers of polyvinylidene fluoride (PVDF) with graphene using near-field electrospinning (NFES) technology. A uniform experimental design table U*7 (7^4 ) was applied, considering weight percentage (1-13 wt%), distance between needle and disk collector (2.1-3.9 mm), and applied voltage (14.5-17.5 kV). We optimized the parameters using electrical property measurements and the Kriging response surface method. Adding 13 wt% graphene significantly improved electrical conductivity, increasing from 17.7 μS/cm for pure PVDF to 187.5 μS/cm. The fiber diameter decreased from 21.4 μm in PVDF/1% graphene to 9.1 μm in PVDF/13% graphene. Adding 5 wt% graphene increased the β-phase content by 6.9%, reaching 65.4% compared to pure PVDF fibers. Material characteristics were investigated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), contact angle measurements, and tensile testing. Optimal parameters included 3.47 wt% graphene, yielding 15.82 mV voltage at 5 Hz and 5 N force (2.04 times pure PVDF). Force testing showed a sensitivity (S) of 7.67493 log(mV/N). Fibers were attached to electrodes for piezoelectric sensor applications. Results affirmed enhanced electrical conductivity, piezoelectric performance, and mechanical strength. The optimized piezoelectric sensor could be applied to measure physiological signals, such as attaching it to the throat under different conditions to measure the output voltage. The force-to-voltage conversion facilitated subsequent analysis.

Age diversity in the workplace is a growing challenge. This study aimed to assess work ability among Family and Community Nurses (FCNs) in a large Local Health Authority (LHA) in Tuscany, Italy. The Work Ability Index (WAI) was administered to 178 FCNs, along with demographic and occupational data. Results showed a significant negative correlation between chronological age and WAI, indicating decreasing work ability with age. Moreover, work setting, educational attainment, and health conditions influenced work ability. Nurses working in home settings and those with higher educational levels reported better work ability. A high prevalence of health conditions, particularly musculoskeletal disorders, was observed. These findings highlight the need for targeted interventions to support FCNs' work ability and address age-related challenges. This study provides a foundation for developing strategies to optimize the nursing workforce and ensure high-quality care delivery.

Present experimental study assesses the mechanical properties of glass/carbon/glass hybrid composite laminates after exposure to moisture and elevated temperatures for extended periods. The top and bottom layers of the hybrid laminates are glass fiber reinforced and the middle layer is carbon fiber reinforced with the matrix specified as a polymer material. The hybrid laminates were manufactured using the resin transfer molding method and their compressive and tensile properties were determined using a tensile testing machine. The material parameters such as the storage modulus, the loss modulus, and the damping factors of the laminates were identified using dynamic mechanical analysis as a function of the temperature and the vibration frequency. The experimental results on compressive and tensile properties revealed slight variations when the hybrid laminates were kept at low temperatures for extended periods. This might occur due to the increasing molecular cross-linking of the polymer network. As the temperature increased, compressive, tensile, storage modules, loss modulus, and damping factors decreased. This might occur due to the increasing mobility of the binder material. Particularly, the highest stiffness parameters were obtained on -80°C/GCG (Glass/Carbon/Glass) laminates due to the presence of beta transition on the glassy region. The relationships between the glass transitions and the targeted frequencies were characterized. The values of the glass transition shift towards higher temperatures as the frequency increases. This might occur due to a reduction in the gaps between the crosslinking of the epoxy network when the frequency increases. The accuracy of the storage modulus results was compared with the empirical models. The model based on the Arrhenius law provided the closest correlation. Meanwhile, another model was observed that was not accurate enough to predict when gamma and beta relaxations occur under a glassy state.

With firm commitment to energy labelling, it is not a question of if but only of when the European Union will introduce an energy label for electric cars. To support such policy efforts, we conducted a scoping analysis of energy consumption and efficiency trade-offs for 342 electric car models sold in Europe. The results suggest that certified and real-world energy consumption average 19 ± 4 kWh/100 km and 21 ± 4 kWh/100 km, translating into drive ranges of 440 ± 120 km and 380 ± 110 km, respectively. Energy consumption is correlated with vehicle mass, frontal area, and battery capacity, but less so with rated power and vehicle price. Each 100 kg of vehicle mass and 0.1 m2 of frontal area tend to increase energy consumption by 0.20 ± 0.06 kWh/100 km and 0.72 ± 0.05 kWh/100 km. Raising battery capacity by 10 kWh increases vehicle mass by 145 kg, energy consumption by 0.6 kWh/100 km, and drive range by 45 km. Efficient vehicles are available at any price but drive range has a cost. Our findings point to considerable efficiency trade-offs that could be tapped by a dedicated energy label. We propose several options for categorizing vehicles on an efficiency scale from A to G, with and without additional utility parameters. Our analysis provides rationale for energy labelling of electric cars in Europe and could inspire similar analyses for other vehicle categories such as e-scooters, lightweight three- and four-wheelers, e-busses, e-trucks, and electric non-road machinery.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of hepatocyte growth factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF's long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold-cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF's bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.

Infrared thermography is a contactless imaging technique, useful to measure surface temperature at distance which has been widely applied in animal production. The possible applications within the pig husbandry include sow heat detection, reduction of the incidence of neonatal mortality, recognition of febrile state caused by pathogens, study of metabolic efficiency, evaluation of stress caused by heat, by constraints, or by aggressive interaction and meat quality prediction. Even if this technique could be easily influenced by environmental factors, the continuous improvement in the procedures and the decrease in the cost of the equipment will allow in the next future new and more applications in swine farming.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

Reducing the carbon footprint of energy production is one of the most pressing challenges facing humanity today. Lignocellulosic biomass residues from fruit production industries show promise as a viable energy source. This paper presents a study of the Italian context concerning the utilization of orchard lignocellulosic residues for energy production as electricity or bioethanol. The potential of various orchard residues was assessed through chemical and physical analysis, and an equivalent electrical energy of about 6441.62 GWh or an amount of 0.48 Mt/y of bioethanol was obtained based on the average annual dry residue mass availability of about 3.04 Mt/y. These data represent the 9.30% of the national electrical energy production from renewable sources, as well as the 6.21% of the Italian demand for gasoline in 2022. Electricity generation from these residues shown its potential as a reliable and sustainable baseload power source, as well as source of renewable transportation fuel. The studied process could be a valuable reference to expand these concepts on global scale to achieve a greener and more sustainable energy future.

It has been empirically observed that the upper tail of the firm size distribution follows either the Pareto distribution or the Zipf distribution, with both patterns being explained by Gibrat’s law (Gabaix, 1999). This article analyzed firm revenue data from China, spanning from 2005 to 2013, to examine the whole range of the firm size distribution. Our empirical analysis revealed that firm revenue data over these years is well fitted by a three-parameter generalized Pareto distribution, with the fitted parameters indicating a dichotomy: The size distribution of large-sized firms, namely the upper tail, is asymptotically characterized by a Pareto distribution or a Zipf distribution, whereas the size distribution of smaller and medium-sized firms is approximated by an exponential distribution. This finding suggests that Gibrat’s law should be extended to account for the emergence of a generalized Pareto distribution.

A hypothesis that the generally accepted value of the LiPON conductivity should be attributed to the absorption and displacement currents is substantiated. The reason is a small contribution of the drift current due to field screening by the electric double layer. The basis for this assumption is the measurement of the LiPON absorption capacitance, according to which its dielectric constant is about 106. An alternative equivalent circuit containing a non-ideal absorption element is proposed and its impedance is calculated. It is shown that the Bode diagrams of the alternative circuit well approximate the experimental curves. Parameters and the magnitude of electric field screening are calculated basing on proposed model of a double electric layer. Considering the screening effect, the drift conductivity of LiPON is obtained, which value is in good agreement with the data on lithium concentration and mobility.

Per- and polyfluoroalkyl substances (PFAS), a large group of developing contaminants, have recently become the subject of increased concern due to their potentially hazardous effects. They are classified as poisonous substances that can be found in a variety of aquatic situations. The widespread usage of PFAS across numerous industries has resulted in a high environmental and biological accumulation of the substance. Identification and elimination of PFAS from the environment is crucial since they are tenacious and have the potential to cause cancer. Traditional methods of PFAS content assessment, while useful in some cases, are often inadequate for continuing environmental control and monitoring. Within academia, there is a noticeable desire for rapid, cost-effective, durable, and readily transportable techniques targeted at detecting PFAS compounds in field settings. As a result, environmental labs and other governmental and non-governmental bodies may start testing more often as mandated by legislation. PFAS-detecting sensors, which offer an innovative solution that can be applied in situ and is affordable and simple to use, have emerged as a promising method for assessment based on the existing research. In addition, it may give administrators and users of water worldwide useful information they can use. This article provides a thorough summary of recent developments, limitations, and performance considerations in PFAS detection sensors. The Surface-enhanced Raman scattering (SERS) method has also been covered because of its excellent sensitivity and specificity for detecting pollutants, making it a potential solution for sensing PFAS. Intelligent sensing systems for PFAS detection should benefit from this research.

Salmonella causes various type of disease worldwide with a remarkable pace. Salmonella enteric serotype typhi (S. typhi), a gram-negative bacterium (only cause disease in man) is the mainly causative agent of Typhoid fever. Typhoid fever is most common in poor and unprivileged developing countries of Asia and Africa. One of the major components of virulence factors produced during salmonella infection is Lipid A, which acts as a potent human immuno-modulator bacterial endotoxin. Regulation of Lipid A biosynthetic pathway occurs at second step, catalyzed by LpxC, a Zn2+ dependent metalloamidase. Systematic Screening of a pool of drug datasets like natural products library from Zinc database, Asinex database, Thiophene analogues fruitfully provided us 3 potent lead molecules s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8 which actively binds with LpxC enzyme and could be developed into sound inhibitors of LpxC enzyme after the application of drug development and processing strategies. Wet lab experimentation is required to validate these results for further use.

Physical properties like shape, volume and size affect the dynamics of biological systems. Along these lines, we focus on the topological properties of biological fluids and their biochemical and physiological outcomes. We take as a paradigmatic example the salivary fluid and describe how its topological features may affect the physiopathology of the oral cavity. Topological approaches assess the general properties of saliva, ignoring small-scale physical details such as density, flow rate, stiffness, viscosity. Specifically, the mucin aggregates scattered in the salivary fluid can be tackled in terms of topological holes, i.e., vortical clusters that modify the direction, flow, impulse, local rate-of-change and velocity of saliva. While the current methodological approaches are inclined to remove the effects of impurities assessing systems as homogeneous structures, we argue that the occurrence of mucins breaks up the salivary fluid’s homogeneity, leading to unexpected biophysical modifications. We suggest that every collected salivary sample is not reliable for accurate clinical and experimental investigation, since it displays highly local as well as variable chemical, physical and biological features, not reflecting the current physiological state of the oral cavity. Therefore, the assessment of a single salivary sample is not fully reproducible and cannot provide information about the biophysical, enzymatic and microbiological content of the whole saliva. In sum, the very topological features of the saliva - such as volume, shape, antipodal cells, vortex area, whirling fluid mass, segmentation, discretization, triangulation, node numbering - produce unnoticed biological consequences and network connectivity features with intriguing operational implications.

The effects of the coolant pulsation and the film cooling with the plasma aerodynamic actuation (PAA) could be herein explored via large eddy simulations. The electrohydrodynamic force derived from the PAA was solved through the phenomenological plasma model. The Strouhal number of the sinusoidal coolant pulsation and the averaged pulsation blowing ratio were 0.25 and 1.0, respectively. Comprehensive analyses were carried out on the time-averaged flow fields, and the results revealed that the pulsed cooling jet might cause a deeper penetration into the crossflow, and this phenomenon could be remarkably mitigated by the downward force of the PAA. Furthermore, because of the coolant pulsation, the counter rotating vortex pair (CRVP) expanded to lifted off the wall less well, and the PAA lessened the negative lift-off impact and entrapment from the CRVP. Then, the spatial-temporal development of the coherent structures was figured out by the alterations of the centerline temperature, reflecting formation of the intermittent coherent structures rather than hairpin vortices due to the coolant pulsation, and their size and upcast behaviors were reduced by the PAA. Consequently, there was a basic suppression of the turbulent mixing of the cooling fluid with the crossflow. Finally, the three-dimensional streamlines confirmed that the coherent structure dynamic behaviors were significantly regulated by the PAA for alleviating the adverse influences of the coolant pulsation. In summary, through controlling how the dominating coherent structures evolve throughout time and space, the PAA can effectively increase the pulsed film cooling efficiency.

Achieving the best aesthetic result is a key objective of implant-prosthetic therapy. To maximize the aesthetic outcome, ensuring that implant-supported restorations are in harmony with the peri-implant soft tissues and bone is essential. A comparative analysis of zirconia and titanium dental implants revealed that both materials offer high success rates; however, they present distinct advantages and limitations in clinical practice. Titanium implants, with surface modifications but without chemical composition changes, boast remarkable long-term survival. In contrast, zirconia implants, while presenting high aesthetic and biocompatibility qualities, have a relatively high incidence of material-specific failure, ranging from 4% to 2% after 5-10 years. While titanium implants generally show superior long-term performance, zirconia implants benefit from ongoing advancements aimed at improving their osseointegration and longevity. This study emphasizes the need for short-term and long-term studies, complemented by randomized controlled trials (RCTs), which are essential for optimizing implant materials and ensuring patient satisfaction. Continued innovation and research are crucial for advancing dental implant technology and enhancing the quality of life for patients requiring dental restorations. Finally, it is important to understand that all materials have both advantages and disadvantages, so the choice of the optimal material should be based on the specific purpose.

Commercial Brazilian wheat flour was subjected to extrusion, oven, and microwave treatments. The solubility, monomeric and polymeric proteins, and glutenin and gliadin profiles of gluten were analyzed. In addition, in vitro digestibility and response against potential celiac disease immune-stimulatory epitopes were investigated. All treatments resulted in low solubility of the polymeric and monomeric proteins. The amounts of insoluble proteins increased from 5.6 % in control flour to approximately 10 % for all treatments, whereas soluble proteins decreased from 6.5 % to less than 0.5 % post treatment. In addition, treatments affected glutenin and gliadin pro-files. The amount of α/β- gliadin extracted decreased after all treatments, while that of γ-gliadin was unaffected. Finally, alteration of the gluten structure and complexity was not sufficient to render a product safe for consumption for individuals with celiac disease; the number of poten-tial celiac disease immune-stimulatory epitopes remained high.

The unravelling of the human genome created new perceptions on the origin and evolution of diseases and for cancer in particular, it established the notion that neoplasia has been a companion of life since its ap-pearance on earth. It is not surprising that neoplasms, in various forms, develop in numerous species of animals and even in plants. Unmistakable accounts of cancer with clinical features as are understood today, begin in the 5th c. B.C. The principles and practice of the Hippocratic and Galenic tradition dominated cancer care virtually into the 20th century. Advanced sequencing technologies at the dawn of the 21st century, generate new ther-apeutic opportunities with immunotherapy, oncolytic virotherapy and gene transfer, the latter especially in cases of hereditary cancer.

The research aimed to identify the effect of high-intensity compound exercises for physical performance skills using the means of hypoxia training in some biochemical variables in the blood of fencing players. The researcher used the experimental approach and determined the community, namely the players of Maysan governorate teams in fencing and for the three weapons (fencing sword, shish, Arab sword) the category of applicants over the age of (20) years, and by (4) players for each weapon, which reached the number of society (12) players, and some procedures were adopted to achieve the objectives of the study. The study came out the results of the study recorded a significant impact on the high level of measurement of blood biochemical variables (EPOs, FERSs, Hb, Hct) and improved by high-intensity compound exercises using the training hypoxic mask among members of the research community.

The cultural transmissions of a society like famous paintings, popular music, good poetry, and enduring religious rituals/doctrines/texts serve as mediums for the embodiment of algorithms that interact with the mind and body in looping, mostly unconscious interactions that are mutually beneficial to the participants of the society and the algorithms themselves. Useful algorithms are also found in the mind and bodies of other people, and individuals in a group can be used to outsource specialized tasks to benefit the society as a whole. Since useful algorithms must be embodied in a medium to work, there are physical limitations to the computations that can be performed in our universe.

Coulomb’s law and Newton’s law of gravitation are formally identical. Is it a mere coincidence? It seems to us that physics has answered yes so far, at least tacitly. We, on the other hand, do not believe in chance. Since the alternative to the fact that the strong similarity is only the result of chance is to believe that it is not, and in this case there must be a reason for this similarity, we have chosen the path of investigating the possibility that the two fields are not distinct, but have a common root that we will try to find. We propose an electrodynamics of electrically neutral bodies based on the hypothesis that the Coulomb constant in the case of attraction between charges of opposite sign is slightly greater than that of the case of repulsion between charges of the same magnitude as the previous ones, but of the same sign. If this difference were to exist, even small to the point of not being directly measurable in the laboratory, it could still produce macroscopic effects detectable in the case of large aggregates of charges, even if globally electrically neutral, as happens in the astronomical field. We deduce the electromagnetism of such a model and show the results obtained applying the theory to some significant cases such the light deflection in a gravitational field, a planet perihelion precession, the power radiated by merging black holes, the behaviour of antimatter in a gravitational field and, when available, we compare the predictions with the experimental data.

Pathogenesis of the connection of HIV-infection and cancer is a nowadays problem for research. More important is also to take into consideration a complexity of abordasions, such as prevention, diagnosis, monitoring, treatment, including control measures. These should be supported by statistical studies that report on restricted or extended geographical areas, to the level of social class and age. In our written text we try to describe from our opinion, strategies in HIV, infection a social and a healthcare problem.

The accurate identification of bacterial infections is critical for effective treatment in intensive care units (ICUs), yet current diagnostic methods face limitations in sensitivity and specificity, along-side cost and accessibility issues. Consequently, there's a pressing need for a marker that is economically feasible, rapid, and reliable. Presepsin (PSP), also known as soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for early sepsis diagnosis. PSP, derived from soluble CD14, reflects the activation of monocytes/macrophages in response to bacterial infec-tions. It has shown potential as a marker of cellular immune response activation against patho-gens, with plasma concentrations increasing during bacterial infections and decreasing post-antibiotic treatment. Unlike traditional markers such as procalcitonin (PCT) and C-reactive protein (CRP), PSP specifically indicates monocyte/macrophage activation in bacterial infections. While limited studies in critical illness have explored PSP's role in sepsis, its diagnostic accuracy varies with threshold values, impacting sensitivity and specificity. Recent meta-analyses suggest PSP's diagnostic potential for sepsis, yet its standalone effectiveness in ICU infection management remains uncertain. This review provides a comprehensive overview of PSP's utility in ICU set-tings, including its diagnostic accuracy, prognostic value, therapeutic implications, challenges, and future directions.

Available options to combat bacterial infections are getting scarce. We require innovative and imaginative approaches to enhance the identification and discovery of effective antimicrobials capable of combating bacteria resistant to multiple or all available drugs. These methods should either directly eliminate the resistant bacteria or influence their viability indirectly by inhibiting their virulence or reducing their resistance to antibacterial agents. One interesting approach is to analyze ancient remedies presumably used to treat bacterial infections, try formulating them, and test them against modern microbes. The field was recently named ancientbiotics. This approach allows us to take advantage of centuries of accumulated empirical knowledge, from several traditional medicines of various ancient cultures across the world. The strategy has already resulted in promising formulations to combat the ESKAPE group of nosocomial pathogens. Moreover, molecular de-extinction consists of genome analysis of extinct species in the search for useful antimicrobials, such as peptides. The de-extinction of simple organisms such as bacteriophages may eventually become a resource for novel tools to combat multidrug-resistant bacteria. In this review, we summarize and discuss the reported antimicrobial effects of ancient remedies and de-extinct molecules known to modern science, and discuss possible new strategies to further harness the potential of past remedies and molecules to help us fight the rise of superbugs.

This study delves into innovative approaches and pragmatic remedies to surmount software access barriers in educational contexts. Financial impediments and limited software installation know-how can impede students from fulfilling course requirements.

We present contrast information, a novel application of some specific cases of relative entropy measures, designed to be useful for cognitive modelling of sequential perception of continuous signals. We explain the relevance of entropy in cognitive modelling of music and language. Then, as a first step to demonstrating the utility of constrast information for that purpose, we show empirically that its discrete case correlates well with existing successful cognitive models in the literature. We explain some interesting properties of constrast information. Finally we propose future work towards a cognitive architecture that uses it.

Immune checkpoint inhibitors (ICI) are a promising form of immunotherapy that has significantly changed the therapeutic landscape for many advanced cancers. They have shown unique clinical benefit against a broad range of tumour types and a strong overall impact on survival in studied patient populations. However, there are still many limitations holding back this immunotherapy from reaching its full potential as a possible curative option for advanced cancer patients. A great deal of research is being undertaken in the hope of driving advancements in this area, building a better understanding of the mechanisms behind immune checkpoint inhibition and ultimately developing more effective, safer, and wider-reaching agents. Taking into account the current literature on this topic, this review aims to explore in depth the basis of the use of ICIs in the treatment of advanced cancers, evaluate its efficacy and safety, consider its current limitations, and finally reflect on what the future holds for this very promising form of cancer immunotherapy.

Some global difficulties in the modern period include energy storage conversion. Researchers have looked to renewable energy resources to discover long-term answers to this dilemma. Fuel cells are one example of prospective energy producing technology. Although these technologies appear to be very enticing, they are known to be expensive due to high expenses. Catalyst costs, as well as concerns concerning energy density. Pt based Electrocatalysts have traditionally been used to drive ORR and offer efficient power outputs. However, cost constraints have limited the use of these electrocatalysts, rendering them inefficient. Apart from the high price, Pt-based Electrodes are prone to time-dependent drift and CO deactivation, both of which occur gradually. Electrocatalysts deteriorate over time, reducing the efficiency of fuel cells. This is why alternative electrocatalysts are in high demand for future energy applications. This review covers the comparative study of Platinium and Non-Platinium based electrocatalyst in fuel cells, their shortcomings and recent advancement for efficient and optimized electrocatalyst.

The Diophantine equation for which p is prime 2^n = p^2 + 7 and n is integers with p > 0, is examined in this work. It is demonstrated by examining the characteristics of the equation that the only solutions meeting these requirements are p = 3 with n = 5 and p = 5 with n = 7. In order to analyze the above equation, it is necessary to look at the properties of primes and how they relate to powers of two. These results advance our knowledge of prime numbers and how they behave in certain mathematical problems.

Many studies have addressed sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying the differences. Cross-sectional study of 203 patients. The clinical and demographic variables included age, years of education, time since onset, smoking, type of treatment, clinical presentation, number of entheses affected, dactylitis, fatigue, and cutaneous involvement. Disease activity,functioning and disease was measured. The comorbid conditions evaluated included obesity (and leptin as an associated parameter), anxiety and depression, and sleep quality. Mean age was 54.6, and 46.8% of patients were women. Women less frequently presented axial involvement and more frequently presented enthesitis. They also presented greater disease activity, greater disease impact, and poorer functioning, as well as greater fatigue. As for comorbid conditions, women presented a higher leptin/BMI ratio, higher levels of anxiety and depression, and poorer sleep quality. By sex, pain affecting women was associated with the leptin/BMI ratio and sleep quality. The leptin/BMI ratio was not associated with any component of disease activity in men. Sex was associated with several clinical manifestations, disease activity, functioning, and disease impact. Leptin was associated with intensity of pain in women.

This exploration delves into the intricacies of decision-making in business management. It covers decision-making models, influencing factors, real-world case studies, and strategies for effectiveness. Emphasizing the role of data-driven approaches, the exploration highlights the transformative impact of effective decisions on organizational success. Challenges and pitfalls are addressed, providing insights for overcoming obstacles. The importance of mastering decision-making is underlined as a strategic advantage in the competitive landscape of business management. In summary, this exploration offers a nuanced understanding, empowering leaders to make informed choices that shape organizational destinies.

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA), a precursor of the cardiovascular inflammatory marker trimethylamine N-oxide (TMAO). Polymethoxyflavones (PMFs), exemplified by tangeretin, demonstrate efficacy in mitigating TMAO-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, exploring its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment attenuated the population of CutC-active bacteria, specifically Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition resulted in reduced efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive action against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.

Abstract: this study aimed to evaluate the benefits of applying 5 cmH2O of CPAP using a pediatric helmet during the recovery phase from general anesthesia in brachycephalic dogs. Brachycephalic dogs undergoing various surgical procedures were included in the study, and a total of 64 subjects were randomly assigned to receive either standard oxygen supplementation (NO-CPAP group) or oxygen supplementation combined with CPAP (CPAP group). The study evaluated arterial blood pH, blood gas partial pressures of O2 and CO2, arterial blood O2 saturation, and related parameters during recovery. The dogs were monitored, and helmet tolerance was assessed using predefined criteria. Of the initially assessed 69 dogs, 64 were enrolled, 32 in the CPAP group and 32 in the NO-CPAP group. Fifteen dogs in the NO-CPAP group were excluded based on predetermined criteria. The CPAP group showed significant improvements in PaO2, PaO2/FiO2, P(A-a)O2, F-Shunt, and respiratory rate compared to the NO-CPAP group (p < 0.001). The incidence of reintubation and helmet intolerance was higher in the NO-CPAP group (18% and 15.6%, respectively) than in the CPAP group (0%). This study highlights the potential benefits of incorporating CPAP, delivered through a pediatric helmet, in the perioperative management of brachycephalic dogs. Keywords: Brachycephalic; dog; CPAP; oxygenation; anesthesia

Traditional aquaculture systems appear to be confronted with the high total ammonia nitrogen (TAN) produced during production, which can be harmful to aquatic life. As the demand for global fish production continues to increase, farmers should adopt Recirculating Aquaculture Systems (RAS) to improve production. The biofilter plays a vital role in ammonia removal. However, the drawback of the biofilter operation is needed an automatic and controlled system with a water quality monitoring system to guarantee optimal performance. RAS utilize a monitoring and control system to maintain the water quality and control the biofilm growth in the biofilter to reduce the ammonia. Therefore, this study focuses on developing a water quality monitoring and control system to achieve optimum biofilm performance. From 35 days of the experiment, the water quality was controlled at a level save for the aquatic environment, such as dissolved oxygen, pH, temperature, and TDS. Thus, the highest TAN removal efficiency is 50% when biofilm thickness reaches 119.88 µm.

Accurate estimation of chlorophyll content in wheat leaves can not only reflect its growth and nutritional status, but also provide a scientific basis for field management. In order to evaluate the potential of hyperspectral data to estimate the chlorophyll content of wheat leaves, this study focused on the leaves of wheat at the flag-picking stage, flowering stage, grain filling stage and maturity stage. Based on the framework of five vegetation indexes, the spectral index was con-structed by using the combination of 400-1000nm bands, and the correlation between the con-structed spectral index and the measured chlorophyll value was analyzed, and the optimal spectral index was screened by the correlation coefficient. Based on the optimal spectral index, polynomial regression, random forest, decision tree and artificial neural network were used to establish the estimation model of chlorophyll value, and the optimal model for estimating the chlorophyll value of wheat leaves was selected through model evaluation. The results showed that the five optimal spectral indices at the four growth stages were mainly composed of red band, red edge band and near-infrared band, and the five optimal spectral indices at the grain filling stage had the highest correlation with the chlorophyll value, and the absolute value of the cor-relation coefficient was greater than 0.73, the accuracy of the estimation model established in the four growth stages was different, and the estimation accuracy of the flag stage was the best, with R² and RMSE of 0.79 and 2.63, respectively. The above results show that hyperspectral data is suitable for estimating the chlorophyll value of wheat leaves, and the PR model of flag picking period can be used as the optimal model for estimating the chlorophyll value of wheat leaves.

This paper deals with the design and kinematic analysis of a novel mechanism for the elbow joint of an upper-limb exoskeleton, with the aim of helping operators, in terms of effort and physical resistance, in carrying out heavy operations. In particular, the proposed eight-bar el-bow joint exoskeleton mechanism consists of a motorized Watt I six-bar linkage and a suitable RP dyad, which connects mechanically the external parts of the human arm with the corre-sponding forearm by hook and loop velcro and thus, helping their closing relative motion for lifting objects during repetitive and heavy operations. This relative motion is not a pure rotation and thus, the upper part of the exoskeleton is fastened to the arm, while the lower part is not rigidly connected to the forearm, but through a prismatic pair which allows both rotation and sliding along the forearm axis. Instead, the human arm is sketched by means of a crossed four-bar linkage, which coupler link is considered as attached to the glyph of the prismatic pair, that is fastened to the forearm. Therefore, the kinematic analysis of the whole ten-bar mecha-nism, which is obtained by joining the Watt I six-bar linkage and the RP dyad to the crossed four-bar linkage, is formulated to investigate the main kinematic performance and for design purposes. The proposed algorithm has given several numerical and graphical results. Finally, a double-parallelogram linkage, as particular case of the Watt I six-bar linkage, was considered in combination with the RP dyad and the crossed four-bar linkage, by giving a first mechanical de-sign and a 3D printed prototype.

Machine-learning methods used for classification are challenged by the class imbalance problem, where a certain class is underrepresented. Over/under-sampling the majority/minority class observations or model selection for ensemble methods alone might not be effective if the class imbalance ratio is very high. To address this concern, a novel method is presented for generating synthetic data for minority class observations in conjunction with an optimal tree ensemble classifier (OTEC). This novel synthetic method first generates minority class instances to balance the training data. Then it applies OTEC, where models are selected based on their performance using out-of-bag observations and training subsamples. A total of 20 benchmark problems on binary classification with moderate to extreme class imbalance are used to assess the efficacy of the proposed method against other well-known methods, including optimal tree ensemble, smote random forest, under-sampling random forest, oversampling random forest, k-nearest-neighbor, support vector machine, tree, and artificial neural network, using classification error rate, sensitivity, specificity, precision, recall and F1-score as performance metrics to assess the efficacy of the proposed method. The analyses presented in this study revealed that the proposed method based on data balancing and model selection yielded better results than other methods.

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain per-iodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tis-sue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL-cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotions of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as il-lustrated by the production of the antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the perio-dontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.

Barley is rich in phenolic compounds, providing health benefits and making it a valuable addition to a balanced diet. However, most studies focus on these compounds at barley's final maturity, neglecting their synthesis during grain development and its impact on barley quality for food applications. This study investigates phenolic profiles during grain development in four hull-less barley genotypes with different grain colors, specifically bred for food applications. The objectives were to determine the phenolic profile and identify the optimal maturity stage for maximum phenolic content and antioxidant capacity. Using UPLC-MS/MS and in-vitro antioxidant capacity assays, results show that total phenolic compounds decrease as grain matures due to increased synthesis of reserve components. Flavan-3-ols, phenolic acids, and flavone glycosides peaked at immature stages, while anthocyanins peaked at physiological maturity. The harvest stage had the lowest phenolic content, with a gradient from black to yellow, purple, and blue genotypes. Antioxidant capacity fluctuated during maturation, correlating positively with phenolic compounds, especially bound phenolic acids and anthocyanins. These findings suggest that early harvesting of immature grain can help retain bioactive compounds, promoting the use of immature barley grains in foods. To support this market, incentives should offset costs associated with decreased grain weight.

In recent years, the utilization of machine learning algorithms and advancements in Unmanned Aerial Vehicle (UAV) technology have marked significant shifts in remote sensing practices. In particular, the integration of machine learning with physical models and their application in UAV-satellite data fusion have emerged as two prominent approaches for estimating vegetation biochemistry. This study evaluates the performance of five machine learning regression algorithms (MLRAs) for mapping crop canopy chlorophyll at the Kellogg Biological Station (KBS) in Michigan, USA, across three scenarios: (1) application to Landsat 7, RapidEye, and PlanetScope satellite images; (2) application to UAV-satellite data fusion; and (3) integration with the PROSAIL radiative transfer model (hybrid methods PROSAIL + MLRAs). The results indicate that the majority of the five MLRAs utilized in UAV-satellite data fusion perform better than the five PROSAIL + MLRAs. The general trend suggests that the integration of satellite data with UAV-derived information, including the normalized difference red-edge index (NDRE), canopy height model, and leaf area index (LAI), significantly enhances the performance of MLRAs. The UAV-RapidEye dataset exhibits the highest coefficient of determination (R2) and the lowest root-mean-square errors (RMSE) when employing kernel ridge regression (KRR) and Gaussian processes regression (GPR) (R2 = 0.89 and 0.89 and RMSE = 8.99 µg/cm2 and 9.65 µg/cm2, respectively). Similar performance is closely observed for the UAV-Landsat and UAV-PlanetScope datasets (R2 = 0.86 and 0.87 for KRR, respectively). For the hybrid models, maximum performance is attained with Landsat data using KRR and GPR (R2 = 0.77 and 0.51 and RMSE = 33.10 µg/cm2 and 42.91 µg/cm2, respectively), followed by R2 = 0.75 and RMSE = 39.78 µg/cm2 for PlanetScope data upon integrating partial least squares regression (PLSR) into the hybrid model. Across all hybrid models, RapidEye data yielded the most stable performance, with R2 ranging from 0.45 to 0.71 and RMSE ranging from 19.16 µg/cm2 to 33.07 µg/cm2. The study highlights the importance of synergizing UAV and satellite data which enables effective monitoring of canopy chlorophyll in small agricultural lands.

Efficient resource allocation is crucial in clusters with frugal Single-Board Computers (SBCs) possessing limited computational resources. These clusters are increasingly being deployed in edge computing environments in resource-constrained settings where energy efficiency and cost-effectiveness are paramount. A major challenge in Hadoop YARN scheduling is load-balancing, as frugal nodes within the cluster can become overwhelmed, resulting in degraded performance and frequent occurrences of out-of-memory errors, ultimately leading to job failures. In this study, we introduce an Adaptive Multi-criteria Selection for Efficient Resource Allocation (AMS-ERA) in Frugal Heterogeneous Hadoop Clusters. Our criterion considers CPU, memory and disk requirements for jobs and aligns the requirements with available resources in the cluster for optimal resource allocation. To validate our approach, we deploy a heterogeneous SBC-based cluster consisting of 11 SBC nodes and conduct several experiments to evaluate the performance using Hadoop wordcount and terasort benchmark for various workload settings. The results are compared to the Hadoop-Fair, FOG and IDaPS scheduling strategies. Our results demonstrate a significant improvement in performance with the proposed AMS-ERA, reducing execution time by 27.2%, 17.4% and 7.6% respectively using terasort and wordcount benchmarks.