LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (>200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p<.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

Today, various dietary supplements are taken to improve endurance performance during physical activity. These supplements have proven to be very successful in controlling and balancing various hormone levels and have contributed to the prevention and healing of metabolic disorders and physical injuries. In this study, we sought to investigate the effects of the ACTN3 gene and nutrient supplementation, including beta-alanine, ashwagandha, L-carnitine, and iron, on athletic performance. The ACTN3 gene has been identified as a potential genetic determinant of athletic performance, particularly in activities that require high levels of power and strength. This study investigated the interaction between the ACTN3 gene and supplementation and highlighted the potential for personalized approaches to improve athletic performance. 24 subjects per group, were randomized in a parallel-group design to examine the effects of supplementation on the ACTN3 gene and athletic performance over a 21-day intervention period. Participants in the intervention were divided into four groups of six members each. The same subjects who did not take supplements formed the control group. In addition, the subjects were divided into 4 groups (G1, G2, G3, and G4), each consisting of subgroups of control and a treated. All treated groups (TG1, TG2, TG3, and TG4) received 4 supplements for 21 days, namely S1 (ashwagandha), S2 (iron), S3 (beta-alanine) and S4 (L-carnitine), together with the 4 control groups, i.e. CG1, CG2, CG3 and CG4, who received no supplements during the same period. In particular, this study determines the effect of these 4 supplements on actn3 gene expression, testosterone, cholesterol and BUN levels of the participants. The P-values determined for all parameters showed statistically significant values and the final result showed that all supplements had positive effects on the tested parameters. The result showed a highly significant difference between the intake of supplements before and after the intake of 24 athletes per group on the ACTN3 gene expression level and biochemical indicators.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P < 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Objectives (Purpose) This study aims to evaluate the outcomes of the Subcrestally Placed Implant (SPI) technique in single molar cases, focusing on biological stability and aesthetics. It proposes a schematic model to elucidate the interplay between the biological stability of soft tissues and bone around the SPI and the morphological requisites that Implant Abutment Prostheses (IAP) must fulfill to effectively replace natural teeth. Materials and methods I examined 20 cases using the SPI technique with Internal Platform Switching (IPS) design implants for single molar replacements to assess their stability. Routine check-ups utilized plain panoramic X-rays to measure changes in crestal bone on the mesial and distal sides. Additionally, 10 cases with CBCT X-rays taken more than one year after the initial surgery underwent a novel 3-dimensional soft tissue analysis (3DSTA). Measurements included placement depths (PD), soft tissue thickness (STT) at central (cPD, cSTT) and peripheral areas (pPD, pSTT), the length of the Transitional Zone (TZ) on mesial, distal, facial, and lingual aspects, and crestal bone thickness (CBT) at buccal and lingual sites. Results Panoramic analyses showed minimal changes in crestal bone (mean changes of pPD were less than 0.1 mm) over an average period of 3.3 years. Average measurements were as follows: cPD was 1.7 mm, pPD was 2.7 mm, cSTT was 0.2 mm, pSTT was 0.6 mm, TZ length was 3.8 mm, buccal CBT was 3.0 mm, and lingual CBT was 3.7 mm. Conclusions CBCT analyses of the topographical relationships between soft tissue and crestal bone with IAP for SPIs demonstrated stable results over an average 3-year period. The consistency in the relationship between crestal bone and surrounding soft tissue can be ascribed to biological structural integrity. The study classified peri-implant soft tissues into subcrestal and supracrestal (transitional zone – TZ) segments, exploring their characteristics through dimensional measurements and assessing mechanical resistance. Further histological study is needed to identify specific features of each segment.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

Effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined and the underlying mechanism of PD-L1 expression elucidated. Initial experiments in human melanoma cells (A375) showed PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

Lysophosphatidic acid (LPA) type 3 (LPA3) receptor mutants were generated in which the sites detected phosphorylated were substituted by non-phosphorylatable amino acids. Substitutions were made in the intracellular loop 3 (IL3 mutant), the carboxyl terminus (Ctail), and both domains (IL3/Ctail). The wild-type (WT) receptor and the mutants were expressed in T-REx HEK293 cells, and the consequences of the substitutions were analyzed employing different functional parameters. Agonist- and LPA-mediated receptor phosphorylation was diminished in the IL3 and Ctail mutants and essentially abolished in the IL3/Ctail mutant, indicating that the main sites were substituted and distributed in both domains. The WT and mutant receptors increased intracellular calcium and ERK 1/2 phosphorylation in response to LPA and PMA. An increase in baseline ERK phosphorylation was detected in the IL3/Ctail mutant. LPA and PMA-induced receptor interaction with β-arrestin 2 and LPA3 internalization were severely diminished in the mutants. Mutant-expressing cells also exhibit increased baseline proliferation and response to different stimuli, which were inhibited by the antagonist Ki16425, suggesting a role of LPA receptors in this process. Migration in response to different attractants was markedly increased in the Ctail mutant, which the Ki16425 antagonist also attenuated.

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

The ubiquitous presence of microplastics (MPs) in the environment poses a threat to ecosystems and increases concerns about their exposure to the human body. However, despite being consumed for health improvement, limited research has been conducted on MPs in functional foods. This study aimed to investigate the occurrence of MPs and the relation of the source of raw material or the manufacture in various omega-3 oil in the Korean market. MPs in omega-3 capsule and raw oil, sourced from both plant-based (PB) and animal-based (AB) sources, were investigated. We developed the method by direct filtration with acetone washing and analyzed MPs greater than 5 μm using microscope-Raman spectroscopy. The average number of MPs was found to be 1.2 ± 1.7 MPs/g for PB raw oil, 2.2 ± 1.7 MPs/g for AB raw oil, 3.5 ± 3.9 MPs/g for PB capsule oil, and 10.6 ± 8.9 MPs/g for AB capsule oil. Polypropylene and polyethylene terephthalate were major specious (83-95 %) found in omega-3 oil. The ratio of size range remained consistent across all groups, with a trend of higher detection rates as the size diminished. The results reveal that the main reason of MPs contamination is not the source of raw material but the manufacturing and packaging process for omega-3 oil.

A comprehensive understanding of the genetic diversity among strains of Xanthomonas citri pv. citri (Xcc), the causative agent of citrus bacterial canker, is crucial for unraveling the pathological nature, structure, and evolution of populations, thereby facilitating the adoption of sustainable control measures. In a collection of 48 strains isolated in 2012, 2020, and 2021 from citrus production areas in Burkina Faso, polymerase chain reaction (PCR) tests utilizing specific primers were conducted to investigate the distribution of type 3 effectors (T3E) and the structuring of strains based on their geographical origins. The analysis of the distribution of type 3 non-transcription activate like effectors (TALE) reveals a more extensive repertoire in strains isolated in 2020 and 2021 compared to those isolated in 2012. Nevertheless, all strains share a common repertoire of three genes, namely XopE2, XopN, and AvrBs2. Additionally, all screened effectors were observed in the Bobo-Dioulasso locality. Concerning the characterization of TALEs, two profiles consisting of two to three TALEs were identified. Profile 1, with two TALEs, was present in 37 Xcc strains, while Profile 2, with three TALEs, was identified in 11 strains. Among the three TALEs (A, B, and C) identified, TALEs B and C were common to all strains. The correlation matrix revealed a positive correlation between the T3E content of strains and the years of their isolation. Multiple component analysis indicated a weak structuring of the tested strains.

Recently, due to the decrease in labor force, increase in labor costs, and the desire for improved quality of life, research on robots has been actively conducted to address these issues. However, it is currently difficult to find robots that physically interact with humans. The reason is that the actuators of robots do not have high torque density on their own. To solve this problem, high torque density motors, such as proprioceptive actuators, are being researched. However, the torque density is still insufficient for physical interaction with humans, so we have developed a motor with higher torque density. However, high torque density motors have the disadvantage of lower speed characteristics due to increased Back-EMF. Therefore, to address the deterioration of speed characteristics in the developed motor, we applied the Independent 3-Phase winding structure to improve the speed characteristics. Consequently, through comparison with Y-Connection and Delta-Connection, we propose the most suitable winding structure for high torque density motors intended for physical interaction with humans.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

Through the use of Smart Sensor Networks (SSN), Marine Observatories (MO) provide continuous ocean monitoring. Deployed sensors may not perform as intended due to the heterogeneity of SSN devices’ hardware and software when combined with the Internet. Hence, SSN are regarded as complex distributed systems. As such, SSN designers will encounter challenges throughout the design phase related to time, complexity, sharing diverse domain experiences (viewpoints), and ensuring optimal performance for the deployed SSN. To this end, we describe in this article how we extended our previously proposed ArchiMO meta-model and design tool by extending an Enterprise Architecture Framework based on the ArchiMate Modeling Language. This extension proposes the incorporation of new Underwater Environmental Constraints (UEC) for SSN in ArchiMO which is coupled with the fusion of sensors with Artificial Intelligence. This serves as the basis for generating a new version of our ArchiMO design tool, which incorporates the new added constraints and invokes the AI created Database. To illustrate our proposal, we use the newly generated ArchiMO to create a model in the MO domain. Furthermore, we use our self-developed domain-specific model compiler to produce the relevant simulation code. Throughout the design phase, our approach contributes to handle and control the uncertainties and variances of the provided quality of service that may occur during the performance of the SSN, hence reducing the design activity’s complexity and time. It provides a way to share the different viewpoints of the designers in the domain of SSN.

Core chlorophytes possess glycerol-3-phosphate dehydrogenases (GPDs) with an unusual bidomain structure, consisting of a glycerol-3-phosphate phosphatase (GPP) domain fused to canonical GPD domains. These plastid-localized enzymes have been implicated in stress responses, being required for the synthesis of glycerol under high salinity and triacylglycerols under nutrient deprivation. However, their regulation under varying environmental conditions is poorly understood. C. reinhardtii transgenic strains expressing constitutively bidomain GPD2 did not accumulate glycerol or triacylglycerols in the absence of any environmental stress. Although, the glycerol contents of both wild type and transgenic strains increased significantly upon exposure to high salinity. Cycloheximide, an inhibitor of cytoplasmic protein synthesis, abolished this response in the wild type. In contrast, GPD2 transgenic strains were still capable of glycerol accumulation when cultured in medium containing cycloheximide and NaCl. Thus, pre-existing GPD2 protein appears to become activated for glycerol synthesis upon salt stress. Interestingly, staurosporine, a non-specific inhibitor of protein kinases, prevented this post-translational GPD2 protein activation. Structural modeling analyses suggested that substantial conformational rearrangements, possibly triggered by high salinity, may characterize an active GPD2 GPP domain. Understanding this mechanism(s) may provide insights into the rapid acclimation responses of microalgae to osmotic/salinity stress.

The combustion of PVC cables in fires results in the release of hydrogen chloride gas. In the European Union, Regulation (EU) No 305/2011, in force since 2017, requires the classification of cables permanently installed in buildings for reaction to fire, smoke, flaming droplets, and acidity. The additional classification for acidity is evaluated through EN 60754-2, involving pH and conductivity measurements. This study focuses on the essential research and development of low-smoke acidity PVC compounds for cables, mainly aiming to meet the stringent additional classifications for acidity, a1 or a2, which cannot be achieved with traditional PVC cables. Understanding the chemistry of thermal decomposition and combustion, especially in the presence of hydrogen chloride scavengers, is crucial for meeting the best acidity classification. The article reviews the current tube furnace tests used in the European Union for cable halogen and acidity assessments. It discusses the limitations of the existing method (EN 60754-2) and highlights the potential of emerging tests such as IEC EN 60754-3, which employs ion chromatography for improved sensitivity and specificity. In the experimental part of the article, various standard and low-smoke acidity cable compounds are tested using tube furnace experiments with different heating regimes. The concentrations of cations and anions in solution are measured through ion chromatography and inductively coupled plasma–optical emission spectrometry. This detailed analysis aims to identify the species influencing pH and conductivity, which is crucial for designing effective acid scavengers that do not impact conductivity. The conclusive results emphasize that HCl from PVC thermal decomposition is the primary driver of pH and conductivity, and the contribution from the decomposition of additives and byproducts from combustion is found to be negligible in most of the tested PVC compounds for cables. The findings underscore the importance of understanding the thermal decomposition of PVC compounds to design acid scavengers capable of trapping hydrogen chloride without adversely impacting conductivity.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon shaped molecule. We analyse the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme 1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH), and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

The main purpose of this article is to consider the smoothness control of a weak solution after some moment if there is known solution regularity until this moment. The necessary tools can be varied. It is possible to control kinetic energy dissipation to fix moment or changing of velocity square or summability of acceleration square to fix at point time.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

This report provides a comprehensive overview of occupational asthma and respiratory hypersensitivity, focusing on some chemicals used in the workplace Includes numerous case studies and research papers related to occupational exposure methacrylates, such as HEMA-HPMA, and respiratory hypersensitivity are discussed And the relationship is explored The book also examines asthma pathophysiology, emerging drug delivery systems used to treat asthma, and the potential of nanoparticles , dendrimers and micellar systems have to improve pulmonary drug delivery in detail The worldwide prevalence of asthma is highlighted, with higher rates in high-GDP countries. The book highlights the need to improve asthma diagnosis, treatment and biomarkers, particularly in rural and low-income countries where the disease is often underdiagnosed and inadequately treated, and discusses the role of inflammation in asthma, in particular secondary inflammation characterized by specific cytokines and inflammation cells In addition, the paper explores various drug delivery methods, such as parenteral and parenteral drugs, pressurized inhalers (pMDIs), dry powder inhalers ( DPIs), nebulizers, nanoparticles, liposomes, micellar systems, microparticles , dendrimers, and gene therapy . These systems aim to increase pulmonary delivery of drugs and improve clinical outcomes. The potential of dendrimer bilirubin-based nanoparticles and micellar systems in the treatment of asthma and lung inflammatory diseases, including asthma, has been discussed in summary, this paper provides an overview of occupational asthma and respiratory hypersensitivity, and this discussion highlights the association between methacrylate exposure and respiratory hypersensitivity.

The aim of this study was to determine the microbial stability, challenge to L. monocytogenes, and some physicochemical properties of turkey breast meat by alginate-based coating enriched with postbiotics (8% concentration, CFS) of Bifidobacterium bifidum DSM 20456 and Bifidobacterium bifidum BB12 strains. For this purpose, firstly, some antimicrobial and total phenolic matter, flavonoid, and DPPH activity values of postbiotics were determined. In addition, FTIR analysis was performed to see the intermolecular interactions of the biological coating agent. As a result of the study, alginate solution with postbiotic showed significant differences in pH, a*, b*, yeast-mold values of turkey meat during storage (7 days), while L* value, total aerobic mesophilic bacteria count (TMAP), psychrotrophic bacteria (PAB), lactic acid bacteria (LAB) and Listeria monocytogenes count were not effective (p>0.05).

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) with proven health effects, whom bioavailability improvement is becoming a public health issue. Unlike fish oils, the bioavailability of DHA from microalgal (A) has not been fully assessed, particularly with regard to the molecular structuring capabilities offered by A-oil. We explored the impact of 5 formulas rich in DHA, different by i) the molecular structure: ethyl ester (EE) or monoglyceride (MG) or Triglyceride (TG) and ii) the supramolecular form: emulsified TG or TG+phospholipids (blend PL), on the lymphatic kinetics of DHA absorption and the lipid characteristics of resulting lipoproteins. We demonstrated that in rat, the DHA absorption of the conventional A-DHA TG structure was more effective than the EE structure (+ 23%). More, the A-DHA MG and A-DHA Emulsion were the most favourable DHA-vectors (AUC: 89% and +42%, respectively), thanks to an improved lipolysis. The A-DHA MG and -Emulsion presented the richest DHA content in TG (+40%) and PL (+50%) of lymphatic chylomicrons, which could impact the metabolic fate of DHA. We concluded that structuring A-DHA in TG or EE would be more prone for tissue and hepatic metabolism whereas in A-DHA MG and A-DHA Emulsion could target nerve tissues.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

To accurately and non-destructively monitor the growth of spring wheat in the Hetao Irrigation Area, UAV remote sensing was employed during various fertility stages. Digital image indices from diverse fertilization treatments were calculated and compared with physiological indices to identify the most sensitive digital image indices corresponding to these indices. The study underscored the critical importance of the flowering stage in the growth of spring wheat, thus highlighting the necessity of focusing on this stage. This finding reiterated that the flowering stage was pivotal for spring wheat development in the Hetao Irrigation Area. Several digital image indices, such as GLA, R, G, INT, g, GRVI, MGRVI, RGBVI, EXG, and GRRI, exhibited a high frequency of significant correlations with physiological indices during the four primary reproductive stages of wheat. Consequently, these sensitive digital image indices during the flowering stage can more effectively characterize the physiological indices of spring wheat.

The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid, and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhytTM) with different human equivalent doses. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

The sustainability of Indigenous Socioecological Systems (ISES) faces significant threats from global anthropogenic environmental changes, endangering Indigenous People (IP), who safeguard a substantial portion of the world's natural capital. Indigenous Traditional Food Systems (ITFS) are crucial within ISES, providing not only diverse and nutritious food but also holding cultural, spiritual, and economic significance. Despite embodying sustainable lifestyles, Indigenous voices remain underrepresented in climate and sustainability discussions. Addressing this gap, the research adopts the Political Ecological Theoretical Framework (PETF) to analyze the regulatory impact on the adaptability, resilience, and sustainability of ITFS. Two Indigenous communities, the Karen in Thailand and various groups in the Republic of Sakha (Yakutia) in Russia, serve as case studies. The study aims to establish a theoretical framework integrating Indigenous concerns into policies and regulations, emphasizing self-determination, cultural preservation, and land rights. Findings emphasize the necessity for comprehensive legal frameworks prioritizing Indigenous involvement in climate resilience and sustainability efforts, moving beyond symbolic gestures towards meaningful collaboration and decision-making power. Recognizing Indigenous vulnerability and engaging them as active partners is essential for navigating climate challenges within ISES and ITFS.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

(1) Background: The aim of study was to investigate the salt consumption by children and adolescents from the Silesian Province (Poland), taking into account the region’s dietary traditions and number of years of school education. (2) Methods : 300 students aged 10–18 from different types of schools, were enrolled in the study and divided into groups in terms of: school, sex, the state of nutrition. The survey questionnaire about dietary habits, including the frequency and serving size with respect to 12 salty products was used. On the basis of the frequency and the amount of consumed products, as well as the data on salt content, the amount of total daily intake of salt was estimated.; (3) Results: The mean daily intake of salt by children and adolescents was 1.083 g ( 0.433 g of sodium); children aged 10–12 consumed the highest amount of salt (1.296 g/day) compared to pupils aged 13–15 (1.131 g of sodium) and adolescents aged 16–18 (0.863 g/day); (4) Conclusions: With age, as a result of various factors, the consumption of salt declines. The parents impact and the familial socio-environmental factors begin to wane, and other factors start to have influence, e.g. school education of healthy lifestyle, health behavior of peers.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K+ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (> 25 mm in diameter) groups. Among the measured K+, Na+, and Cl- concentrations in follicular fluid (FF) obtained from small-sized follicles (SF) and large-sized follicles (LF), the K+ concentration was significantly lower in LFFF. Quantitative PCR, western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in both LF and granulosa cells obtained from LF (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membrane of GCs. The diameter of LFGCs was larger than that of SFGC. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LF is associated with the inhibition of GC growth, leading to senescence and cyst formation.

Abstract: Cervical cancer, which is the fourth most common malignancy and the fourth greatest cause of cancer-related deaths in women globally, continues to be a serious issue for global health. Despite advancements in treatment techniques, particularly the implementation of concomitant chemoradiation therapy, predicting the prognosis of locally advanced cervical cancer, especially for stage III, remains challenging. In recent years, neoadjuvant chemotherapy (NACT) has gained interest as a viable treatment strategy. The objective of this review paper is to scrutinize the clinical data and outcomes associated with NACT in the management of stage 3 cervical cancer. Electronic databases were used to perform a comprehensive literature search, and research up to 2023 were included. The findings suggest that NACT followed by irradiation may have advantages such as lowering tumor size, pelvic architectural distortion, and subclinical distant metastases, therefore enhancing radiation delivery. However, several studies have produced conflicting findings, raising questions regarding toxicity and finding no appreciable survival benefit over radiation alone. NACT followed by radical surgery has demonstrated more promising outcomes compared to surgery alone in terms of increasing rates of overall survival (OS) and progression-free survival (PFS). Additionally, NACT has been associated with decreased tumor growth, parametrial infiltration, nodal, metastases, and vascular space invasion. These findings suggest adjuvant radiation treatment. Although the overall survival rate has been markedly increased by concomitant chemoradiation treatment, metastatic disease continues to be a major factor in the death rate from cervical cancer. Therefore, improving outcomes in locally advanced cervical cancer requires investigating novel systemic treatments, such as NACT. The study also emphasizes how crucial it is to research factors like cisplatin dose-intensity and cycle lengths in order to maximize NACT's efficacy. To prevent the need for subsequent treatments and cumulative toxicity, more study should concentrate on patient selection for NACT followed by surgery.

This article utilized electrodeposition technology to fabricate Zn and Zn-Y₂O₃-Al₂O₃ composite coatings on Q235 steel plates. The composite coatings were obtained by adding Y₂O₃/Al₂O₃ nanoparticles (0, 5, 10, and 15 g/L) to acidic chloride solutions. This study then examined the impact of these nanoparticles on the microstructure, morphology, microhardness, hydrophobicity, and corrosion resistance of the composite coatings. The results indicate that the addition of the nanoparticles increased the nucleation sites on the surface of the coating, thereby refining the grain size and reducing the roughness of the coating surface. When 10g/L of Y₂O₃ and 10g/L of Al₂O₃ nanoparticles were added, the hardness of the composite coating (369 Hv) was 2.49 times higher than that of the pure Zn coating (148 Hv), which was attributed to the dispersion strengthening and grain refinement effects of the nanoparticles. The corrosion resistance of the Zn and Zn-Y₂O₃-Al₂O₃ composite coatings was studied using linear sweep voltammetry and AC impedance spectroscopy. The addition of the nanoparticles improved the corrosion resistance of the composite coating, and the composite coating prepared in an electrolyte containing 10 g/L of Y₂O₃ and 10 g/L of Al₂O₃ nanoparticles exhibited the best corrosion resistance. Meanwhile, the composite coating exhibited good hydrophobicity, with a contact angle of 120.9°, 1.94 times that of the pure Zn coating (62.2°). The Zn-Y₂O₃-Al₂O₃ nanocomposite coating material has significant potential advantages in the field of steel corrosion.

Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNA, that once incorporated in EVs is protected from enzymatic degradation. The possible use of EVs as carriers for vaccine has been investigated showing that EVs expressing recombinant SARS-CoV-2 S protein induced an immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have advantages in conferring long lasting immunization and lower toxicity than synthetic nanoparticles. To overcome the manufacturing limitations of EVs derived from eukaryotic cells, edible plant-derived EVs have been studied as an attractive alternative for vaccine delivery, especially for mucosal administration. We recently showed that EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation and were stable at room temperature for one year. Lyophilized oEVs containing the S1 mRNA were administered to rats by gavage and they induced a specific humoral immune response with generation of blocking antibodies, including IgA, that are the first mucosal barrier in the adaptive immune response. Moreover, a Th1 cytokine secretion occurred, suggesting a specific lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and the ability to stimulate a humoral and cellular immune response.

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

A new approach is presented for dynamic modeling of chemical and isotopic evolution of C1-3 during the hydrocarbon generation process. Based on systematic data obtained from published papers for pyrolysis of various hydrocarbon sources(type I kerogen/source rock, type II kerogen/source rock, type III kerogen/source rock, crude oil, asphalt, etc), the empirical evolution framework of chemical and isotopic composition of C1-3 during the hydrocarbon generation process was built. Although the empirical framework was built only by fitting large amount of pyrolysis data, the chemical and isotopic composition of C1-3 derived from the pyrolysis experiments all follow the evolution laws, convincing us that it is applicable to the thermal evolution process of various hydrocarbon sources. Based on the simplified formula of the isotopic composition of mixed natural gas at different maturities (δ13Cmixed) δ13Cmixed=(X〖*n〗_iA 〖*δ〗^13 C_iA+Y〖*n〗_iB 〖*δ〗^13 C_iB)/(X〖*n〗_iA+Y〖*n〗_iB ), it can be derived that the cumulative isotopic composition of alkane generated in certain maturity interval can be expressed by the integral of the product of instantaneous isotopic composition and instantaneous yield at certain maturity point, and then divided by the cumulative yield of alkane generated in corresponding maturity interval. Thus, the cumulative isotopic composition(A(X)), cumulative yield(B(X)), instantaneous isotope(C(X)),and instantaneous yield(D(x)) in the dynamic model comply with the following formula during the maturity interval of (X0-X) A(X)=(∫_(X_0)^X▒〖C(X)*D(X)dx〗)/(B(X)), where A(X) and B(X) can be obtained by fitting of pyrolysis data, and D(x) can also be obtained from the derivation of B(X). The dynamic model was applied on the pyrolysis data of Pingliang Shale to illustrate the quantitative evolution of cumulative yield ,instantaneous yield, cumulative isotope and instantaneous isotope of C1-3 with increasing maturity.The dynamic model can quantify the yield of methane, ethane and propane as well as δ13C1, δ13C2 and δ13C3 respectively during the hydrocarbon generation process, which is of great significance to evaluate the natural gas resources of hydrocarbon source rock with different maturity and to identify the origin and evolutionary process of hydrocarbons by chemical and isotopic data. Moreover, this model provides an approach to study the dynamic evolution of isotope series of C1-3 (including reversed isotopic series), which is hopeful to reveal the mechanism responsible for isotopic reversal when combined with post-generation studies.

In ore regions impacted by mining and metal smelting emissions, distinguishing between geogenic anoma-lies and anthropogenic contamination poses a significant challenge. In a study from two areas with different mining histories in the Ore Mountains, Czech Republic, we demonstrate that targeted sampling of topsoils and subsoils respecting local geology and correct soil data treatment respecting soil textural variability effects are indispensable to correctly construct and interpret geochemical maps and identify anthropogenic contam-ination by As, Cu, Pb, and Zn. The list of analysed elements must include both potentially toxic and lithogenic elements, otherwise natural controls of soil composition cannot be deciphered. By using empirical cumulative distribution functions, we found that local backgrounds for As/Fe and Pb/Ti are significantly naturally ele-vated (5.7 to 9.8 times and 2.1 to 2.7 times higher, respectively) compared to the global averages. We con-structed geochemical maps with topsoil minus subsoil concentrations to show the main directions of spreading anthropogenic contamination. The anthropogenic diffuse contamination contribution was calcu-lated (1.12·10-4 and 1.42·10-4 for As/Fe and 16.5·10-4 and 16.2·10-4 for Pb/Ti, respectively), which corresponds to topsoil enrichment by ca. 15 and 14 mg kg-1 for As and ca. 35 and 42 mg kg-1 for Pb in the two study areas. Our study thus provided the first published quantitative estimates of geogenic and anthropogenic contribution to this well-known montane area. The obtained estimates were comparable to the results obtained previously from the local peat archives. The approach we used is efficient in deciphering natural and anthropogenic controls of PTEs in geochemically complicated areas.

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148bp fragment showing particularly strong expression in gill and intestine. It was sequenced and represented a piece of the AQP11 gene. However, as the fragment may have resulted from contaminating genomic DNA (in total RNA used to make cDNA), 5’ and 3’ RACE was performed to amplify the two ends of the putative cDNA. 5’ and 3’ RACE amplifications depend on the presence of a 5’ cap nucleotide and a poly A tail respectively on the putative AQP11 mRNA. Hence successful amplification was only possible from cDNA and not genomic DNA. Nested RACE amplifications were performed using gill and intestinal RACE cDNA but none of the DNA fragments were AQP11. Consequently, the spiny dogfish AQP11 gene may represent a pseudogene.

The thermoelectric generator (TEG) has much potential as a renewable energy technology that could be used in ocean thermal energy conversion (OTEC). This technique employs TEGs and heat exchangers as substitutes for the intricate elements found in conventional OTEC systems, including pressure valves, evaporators, condensers, and turbine generators. By harnessing the temperature difference between warm surface seawater and cold deep seawater, it facilitates the conversion of this thermal gradient into electrical energy. This study used computer simulations to look at and compare three different types of heat exchangers: a cavity-type heat exchanger, a heat exchanger with flat fins, and a heat exchanger with longitudinal vortex generators (LVGs). The objective was to evaluate the influence of these designs on the thermoelectric conversion performance when implemented in OTEC systems. The study's findings indicate that using heat exchanger configurations featuring flat fins, or LVGs, enhances the efficiency of thermal energy transfer from warm seawater to TEGs, resulting in a notable enhancement in the output power of TEGs. Furthermore, the efficiency of TEG thermoelectric conversion is influenced by varying seawater flow rates in relation to the performance of flat fins and LVGs. In contrast to the cavity-type heat exchanger, the utilization of a heat exchanger equipped with flat fins has been found to yield a notable enhancement in the output power of TEGs by approximately 22.92%. Furthermore, this configuration demonstrates a substantial improvement in thermoelectric conversion efficiency, exhibiting an increase of around 40.01%. These improvements are observed under certain conditions pertaining to flow rates and fin heights. Utilizing heat exchangers equipped with LVGs has been found to enhance the output power of TEGs by 13.02% and improve the overall thermoelectric conversion efficiency by 17.72%. These improvements are observed under certain conditions, including specific flow rates, LVG tilt angles, and locations.

The hepatitis E virus (HEV) is a zoonotic pathogen with a variety of hosts, including pigs, which act as reservoirs. In industrialized countries, sporadic cases caused by genotype 3, contracted by ingestion of contaminated uncooked or undercooked meat, have been reported. However, in developing countries, HEV infection is mainly dominated by genotype 2 and often associated with poor hygiene conditions and drinking water supplies. In West Africa, HEV infection and its circulation in domestic fauna are very poorly documented. The aim of this study was to assess the presence of HEV in pork sold in Saint-Louis. Meat products were collected between 20 and 25 August 2022 in three location of Saint-Louis region. After purchasing 250 g of sample, we minced 2 g of sample for extraction of total nucleic acids using the Purelink™ Viral DNA/RNA kit and then RT-PCR using the One-Taq™ One-Step RT-PCR kit targeting the HEV ORF2 genomic region. The products obtained were visualized on a 1% agarose gel. Of a total of 74 samples, divided into pork meat (n=65) and pork liver (n=9), 5.4% (n=4) were tested positive for HEV. In both cases, 2 samples were positive, representing a rate of 3.1% and 22.2% for meat and pork liver respectively. All new viral sequences obtained form a monophyletic group within HEV genotype 3. These preliminary results reveal a potential circulation of HEV in the pig population. The high proportion of contamination in the pork liver samples highlights a major risk associated with their consumption.

\abstract{The existence of vorticies is well known in fluid mechanics and particularly in turbulence theory. In the context of the millennium problem of the Clay Institute on the existence (or not) of Global solutions in time of the Periodic Navier Stokes equations (PNS) results are now proposed to confirm that Global solutions do not exist in the general case of PNS defined on $\mathbb{T}^3$. This corresponds to part ($D$) proposition in the Navier Stokes problem as posted by C.Fefferman. Recent work has shown that for the Euler equations defined on the 3-Torus there exists a H\"older continuous solution for the third component of velocity $v_3$ at the center of each cell or cube of the 3-Torus Lattice. It has also been determined that as the kinematic viscosity changes from the corresponding value at $\nu=0$ to the fully viscous case for the Periodic Navier Stokes equations (PNS) at the value $\nu=1$ the solution reaches a peak ($\frac{\partial v_3}{\partial y_3} = 0$ ) in $y_3$. (third component of $\vec{r}=(y_1,y_2,y_3)$ in Cartesian co-ordinates) Here in the viscous case there exists a dipole which is not centered at the center of the cell of the Lattice. This immediately implies that since the dipole by definition has an equal in magnitude positive and negative peak in the third component of velocity, then the dipole Riemann cut-off surface is covered by a closed surface which is the sphere $\|\vec{r}\|=1$ and where a given cell of dimensions $[-1,1]^3$ is circumscribed on a sphere of radius $1$. For such a closed surface containing a dipole it necessarily follows that the flux at the surface of the sphere of $v_3$ wrt to surface normal $\vec{n}$ is zero including at $y_i, i=1\dots 3$ is zero at the points where the surface of sphere touches the cube walls. At the finite time singularity on the sphere a rotation boundary condition is deduced. Here $\frac{\partial v_3}{\partial \vec{n}}= \vec{n}\cdot \nabla v_3$. Also a boundary condition on the sphere shows rotation of sphere. Finally as a result, on the sphere a solution for $v_3$ is obtained which is proven to be H\"older continuous and it is proven that it is possible to extend H\"older continuity on the sphere uniquely to all of the interior of the ball.}

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease- like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little is known about the role of CatB in Pg virulence factor-induced IL-1β production by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with Pg LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human β-defensin 3 (hBD3). IL-1β production in BV-2 microglia induced by Pg LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited Pg LPS-induced IL-1β production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1β production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked Pg LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on Pg virulence factor-induced IL-1β production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1β production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that Pg LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1β without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1β through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1β-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Results showed that mulberry leaves could significantly reduce backfat thickness (P&lt;0.05) and increase intramuscular fat (IMF) content (P&lt;0.05). Lipidomics analysis showed that mulberry leaves improved lipid profile composition and increased the proportion of triglycerides (TG). Interestingly, IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG−005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, Limosilactobacillus, and so on. At the same time improve the L-tyrosine-baton rouge ester, Oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, Mulberrin relative abundance. In this study, we found that mulberry leaves could extremely significantly increasing the mRNA relative expression of lipoprotein lipase (LPL), fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ) in muscle (P＜0.01), significantly increasing mRNA relative expression of diacylglycerol acyltransferase 1 (DGAT1) (P＜0.05) and significantly decreasing the mRNA relative expression of acetyl CoA carboxylase (ACC) (P＜0.05), and aignificantly upregulated hormone-sensitive triglyceride lipase (HSL), peroxisome proliferators-activated receptor α (PPARα) mRNA relative expression (P＜0.05) in backfat. In addition mulberry leaves could increased serum leptin and adiponectin (P＜0.01). Ultimately lead to up-regulation of IMF and down-regulation of backfat.

We analyzed mineralogical characteristics, and major as well as rare earth element concentrations from a cryptotephra layer in sediments of the infilled maar of Auel (Eifel, Germany). The results of detailed geochemical analyses of clinopyroxenes and their glassy rim of the specific layer are most similar to those from the Campanian Ignimbrite (CI) Tephra occurrence in a loess section at Urluia (Romania). Both records show idiomorphic green clinopyroxenes and formation of twisted minerals up to millimeter scale. The cryptotephra in the Auel core has an age of around 39,940 yr b2k in the ELSA-20 chronology, almost identical to the latest Ar/Ar dates for the Campanian Ignimbrite/Y5 eruption. These observations suggest that parts of the CI ash cloud were transported also northwestward into Central Europe, whereas the main branch of the CI ash plume was transported from southern Italy towards the NE, E and SE.

This paper outlines the evolution of a learning technology interface from a Beta version to launch with educators and its alignment to pedagogical theory, designed to maximise collaboration between teacher and student. It explores how the “co-creation” of curricula via textual sources that underpin teaching and learning can be enhanced through interactive e-books and outlines the challenges involved in this praxis. With a number of stakeholders involved in the live use of the platform (including teachers, students, HE educators, course instructors, curriculum designers and software developers), iterative feedback loops informed real-time design improvements to both the interface and the-ory. This collaboration utilised a design-based research (DBR) approach (Wang and Hannafin, 2005), which is outlined here as explanation of how the tool developed and how iterative feedback helped to reconsider the challenges educators face in implementing pedagogical innovation across differing contexts. We propose how speculative design (Lukens and DiSalvo, 2012) and Activity Theory (Engeström, 1987) workshops can methodologically enhance the planning and evaluation phases inherent to DBR approaches, which involve students to prepare for educators’ innovation. Finally, we conclude with how educators can utilise these design principles using stratified approaches to help prepare organisational approaches for innovation.

Alzheimer's disease (AD) is characterized by abnormal amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-PET or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for non-invasive and cost-effective detection of brain Aβ accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aβ42/Aβ40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n=88) and some volunteers (n=66) were subject to evaluation of amyloid status by CSF Aβ quantification or PET analysis. Thresholds of plasma Aβ42/Aβ40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

Predicting and evaluating the vitality level of public spaces of urban design is crucial before new construction and renewal, especially for developing countries, to avoid failures like "ghost neighborhood" and reduce resource waste. However, existing assessment methods for the urban vitality are either static and ignore changes in the time dimension, or rely on historical big data and are unable to predict unbuilt projects. This study combines previous methods and crowds’ characteristics observation in public space, puts forward the crowd-frequency hypothesis and constructs an algorithm, and establishes a time-dimensional urban vitality dynamic prediction model. Taking the Rundle Mall neighborhood in Adelaide, Australia, as an example, the effec-tiveness of the prediction model was proved through on-site observation sampling comparative verification method. In addition, the decision tree model was used to conduct machine learning on the case data, and a set of algorithm programs were obtained that can directly input some basic information to obtain the urban vitality level (high-medium-low) in a certain period. It can be used as a tool to support the design and decision-making processes of urban planners and government officials, providing a low-cost way to achieve sustainable urban vitality construction of late-developing cities directly.

This study employs molecular docking experiments to investigate the binding interactions of Hypericin with key proteins implicated in Alzheimer's disease (AD). Hypericin demonstrated a significant binding energy of -10.1 kcal/mol with ABAD (3-hydroxyacyl-CoA dehydrogenase type II). The analysis revealed multiple binding interactions, including hydrogen bonds with arginine 6, serine 7, and glutamic acid 140, as well as hydrophobic bonds involving leucine 11, aspartic acid 142, and aspartic acid 86. These findings illuminate the intricate molecular interactions between Hypericin and ABAD, suggesting its potential as a lead compound for further therapeutic development in the context of Alzheimer's disease. Additionally, a parallel docking investigation was conducted for Beta-secretase 1 (BACE1), a protein pivotal in the generation of beta-amyloid peptides—a hallmark of Alzheimer's disease. Inhibiting BACE1 activity is considered a promising therapeutic strategy for AD. Computational analyses suggest that Hypericin may serve as a potential inhibitor of BACE1. Molecular Docking results reveal a robust binding affinity between Hypericin and BACE1, supported by a significant binding energy score of -10.3 kcal/mol. Notably, both ABAD and BACE1 exhibit high binding affinity with Hypericin. This theoretical exploration provides an initial understanding of the intricate molecular pathways involved in Alzheimer's disease and proposes Hypericin as a potential therapeutic compound for mitigating its progression.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

Marine lipids are recognized for their health promoting features, mainly for being the primary sources of omega-3 fatty acids, and therefore critical for human nutrition in an age when the global supply for these nutrients is experiencing an unprecedent pressure due to an ever-increasing demand. The seafood industry originates a considerable yield of co-products worldwide that, while already explored for other purposes, remain mostly undervalued as sustainable sources of healthy lipids, often being explored for low value oil production. These co-products are especially appealing as lipid sources since, besides the well-known nutritional upside of marine animal fat, particularly rich in omega-3 polyunsaturated fatty acids (PUFAs), they have also interesting bioactive properties, which may garner them further interest, not only as food, but also for other high-end applications. Besides the added value that these co-products may represent as valuable lipid sources, there is also the obvious ecological upside of reducing seafood industry waste. In this sense, repurposing these bioresources will contribute to a more sustainable use of marine animal food, reducing the strain on already heavily depleted seafood stocks. Therefore, untapping the potential of marine animal co-products as valuable lipid sources aligns with both health and environmental goals by guaranteeing additional sources of healthy lipids and promoting more eco-conscious practices.

This research provides a computationally efficient numerical tool for predicting 3-D turbulent flows over hydrofoils. It addresses a gap in existing numerical methods by extending the capabilities of the laminar VIScous Vorticity Equation (VISVE) solver to handle 3-D turbulent flow scenarios. The implementation integrates the k − ω SST model into the 3-D VISVE solver using the Finite Volume Method (FVM), extending its capability to handle turbulent flows. The turbulence model is also parallelized to improve computational efficiency. The application of the newly developed model to 3-D hydrofoil cases expands its scope and serves as preparatory work for future rotational propeller applications. Rigorous testing includes a convergence analysis concerning grid numbers and time step sizes, and validation against a Reynolds-Averaged Navier-Stokes (RANS) solver ensures the reliability and accuracy of the enhanced VISVE solver for turbulent flow simulations. The turbulent VISVE solver offers advantages such as reduced computational domain and costs through a vorticity-based approach. Turbulence concentration within boundary layers and free shear flows does not compromise the advantages of the small computational domain. The simplified meshing process, automatically generated by denoting the number of panels on the hydrofoil, makes the solver accessible for researchers and engineers.

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel-Lindau tumour suppressor protein (pVHL) and the ubiquitin-proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation.

Delivery systems of the biologically active substance such as proanthocyanidins (PCAN) produced through the electrospinning method were designed using a blend of poly(L-lactide-co-glycolide) and poly[(R,S)-3-hydroxybutyrate]. The research involved the structural and thermal characteristics of the developed electrospun three-dimensional fiber matrix, as well as hydrolytic degradation tests performed on them. Additionally, the release profile of PCAN from the electrospun nonwoven was determined using UV–VIS spectroscopy. Approximately 30% of PCAN was released from the tested electrospun nonwoven during the initial 15-20 days of incubation. The chemical structure of water-soluble oligomers that were formed after the hydrolytic degradation of the developed delivery system was identified through electrospray ionization mass spectrometry. Oligomers of lactic acid and OLAGA oligocopolyester, as well as oligo-3-hydroxybutyrate terminated with hydroxyl and carboxyl end groups, were recognized as degradation products released into the water during the incubation time. It was also demonstrated that variations in the degradation rate of individual mat components influenced the degradation pattern, and the number of formed oligomers. The obtained results suggest that the incorporation of proanthocyanidins into the system slowed down the hydrolytic degradation process of the poly(L-lactide-co-glycolide)/poly[(R,S)-3-hydroxybutyrate] three-dimensional fiber matrix. In addition, in vitro cytotoxicity and antimicrobial studies advocate the use of PCAN for biomedical applications with promising antimicrobial activity.

With the development of modern industry, the issue of water pollution has garnered increasing attention. Photocatalysis, as a novel green environmental technology that is resource-efficient, environmentally friendly, and highly promising, has found extensive applications in the field of organic pollutant treatment. However, common semiconductor materials exhibit relatively low photocatalytic efficiency in the visible light range or inefficient separation of photogenerated charges, resulting in their limited ability to harness solar energy effectively. Consequently, the development of new photocatalysts has become a pivotal focus in current photocatalysis research to enhance solar energy utilization. This revision provides a brief explanation of the photocatalytic mechanism of the AgIO3/CTF heterojunction photocatalyst. Due to the Localized surface plasmon resonance (LSPR) effect, Ag nanoparticles demonstrate significant absorption in the visible light region, playing a crucial role in the highly efficient photocatalytic reduction of organic pollutants.

The historical and cultural use of food as a remedy for diseases is evident in societies, such as using Hibiscus sabdariffa to address conditions like hypertension and high blood glucose. The natural biocompounds in this plant, including Delphinidin-3-Sambubioside (DS3), Quercetin (QRC), and Hibiscus Acid (HA), have been linked to various health benefits. Despite individual attention, molecular targets for these compounds remain unclear. In this study, in-silico analysis employed bioinformatic tools; including Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb, to identify molecular targets, pathways, and hub genes. A PubMed literature search complemented the results. DS3 demonstrated potential modifications in genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation, particularly affecting the PI3K-AKT pathway. QRC displayed interconnected targets across multiple pathways, with overlap with DS3 and a focus on cancer-related pathways. HA showed distinct targets, particularly associated with nervous system-related pathways. These findings highlight the need for targeted research on the molecular effects of DS3, QRC, and HA, providing valuable insights into potential therapeutic pathways.

Inflammation is a conserved process that involve the activation of immune and non-immune cells aiming at protecting the host from bacteria, viruses, toxins and injury. However, unresolved inflammation and permanent release of pro-inflammatory mediators are responsible for the promotion of a condition called “low-grade systemic chronic inflammation”, characterized by tissue and organ damages, metabolic changes and increased susceptibility to non-communicable diseases. Several studies have demonstrated that different dietary components may influence modifiable risk factors for diverse chronic human pathologies. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are well recognized anti-inflammatory and immunomodulatory agents able to influence many aspects of the inflammatory process. The aim of this article is to review the recent literature that relates to the modulation of human disease, such as rheumatoid arthritis, by n-3 PUFAs.

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

Recently, the Third Generation Partnership Project (3GPP) introduced the New Radio (NR) technology for Vehicle-to-everything (V2X) communication to enable delay-sensitive and bandwidth-hungry applications in vehicular communication. The NR system is strategically crafted to complement the existing Long Term Evolution (LTE) Cellular-Vehicle-to-Everything (C-V2X) infrastructure, particularly to support advanced services such as the operation of automated vehicles. It is widely anticipated that the 5th generation (5G) NR system will surpass LTE C-V2X in terms of achieving superior performance in scenarios characterized by high throughput, low latency, and enhanced reliability, especially in the context of congested traffic conditions and a diverse range of vehicular applications. This article will provide a comprehensive literature review on vehicular communications from Dedicated Short Range Communication (DSRC) to NR V2X. Subsequently, it delves into a detailed examination of the challenges and opportunities inherent in NR V2X technology. Finally, we proceed to elucidate the process of creating and analyzing an open-source 5G NR V2X module in network simulation-3 (ns-3) and then demonstrate the NR V2X performance in terms of different key performance indicators implemented through diverse operational scenarios.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

This study presents the design and implementation of a PLC microprocessor adhering to the IEC-61131-3 standard, executed on a Cyclone-V FPGA using a DE10-NANO development board. Our microprocessor optimizes the central processing unit by streamlining the data path, achieving a remarkable simulated response time of approximately 60 ns, equivalent to three clock cycles at a 50MHz frequency for Boolean operations. To substantiate our approach, we conducted practical experiments utilizing a FESTO conveyor station, employing relays as actuators, and incorporating optical and inductive sensors. The results underscore the feasibility of our proposed approach and serve as practical validation of its efficacy. This work introduces a promising avenue for the development of cost-effective PLCs employing SoC FPGA variants. Additionally, a thorough comparison of execution times with other early reported architectures. Our microprocessor outperforms even well-established PLCs like the S7-312, with substantial reductions in execution times of 94.54% for floating-point operations, 71.42% to 93.33% for word operations, and up to 78.57% for bit operations.

Air pollution has been a major environmental issue worldwide from the last few decades. It is a man-made issue that has a serious harmful impact on the environment and the health of humans. There are different sources of emission, but industrial processes and motor vehicles contribute to a chief part of air pollution. It has acute as well as chronic effects on the health of humans and affects different organs. It is thought the main environmental risk factor in the incidence and progression of several diseases such as lung cancer, asthma, Alzheimer's and Parkinson's diseases. Long-term exposure to air pollution has different toxicological impacts on humans such as respiratory and cardiovascular diseases, neuropsychiatric complications, eye irritation and skin diseases. As per the study by the World Health Organization (WHO), nitrogen oxides (NOx), carbon monoxide (CO), ozone (O₃), sulfur dioxide (SO₂), volatile organic compounds (VOCs) and heavy metals are the major air contaminants. These pollutants are different in their properties, composition and time of disintegration. The aim of this study is to review the different sources, types, impacts, challenges and mitigation of air pollution in detail.

Development of new techniques of multimodal treatment, diagnostics of various neoplasms and improvement of these techniques can significantly increase the life expectancy of patients with carcinomas of the colon and abdominal cavity organs, since prevention of various side effects of radiation therapy is one of the main problems of oncological care. Electron irradiation is one of the most promising types of radiation therapy. There are no data on proliferation and apoptosis of the colon epithelium after irradiation with electrons, especially in different modes (single and summary). Aim of the study: Morphological evaluation of apoptosis and proliferation of colonic epithelium after local irradiation with electrons at doses 2 Gy and 25 Gy. Materials and methods. Colon fragments from sexually mature Wistar rats (n=50, body weight 200 ± 10 g) were divided into three groups: I - control (n = 10); II - experimental group (n = 20; local single electron irradiation at a dose of 2 Gy), III - experimental group (n=30), local fractional irradiation with electrons at a total dose of 25 Gy. They were studied by light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and Cas3. Morphological disorders were accompanied by increased expression of pro-apoptotic molecules (caspase-3), and the period of regeneration by proliferative marker (Ki-67). Conclusions: Local fractional irradiation of the colon with electrons at a dose of 2 Gy and 25 Gy resulted in minor changes in the epithelium, a decrease in the number of goblet cells, but with preservation of regenerative potential, mild degenerative-dystrophic lesions. Intestinal crypts were damaged, leading to a decrease in Ki-67 and an increase in the number of caspase-3-positive epitheliocytes.

Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.

Hip joint surgeries, including total hip replacement or resurfacing, have increased tremendously in the last decades. Number of patients of all ages, replace their hip, due to severe injuries or trauma problems, so as to have a better life. According to these factors, new material and processes in implants manufacturing are imported to medicine, through research programs, every year. In the scope of one of these programs, that has to do with ceramic coatings on metallic resurfacing implants, a new 3axis Hip simulator was designed and manufactured in the Laboratory of Manufacturing Technology of the National Technical University of Athens. The scope of this paper is to present the main parts, materials and process used to manufacture the simulator as well as the way the simulator is working and how its movement in 3axis is accomplished. Furthermore, the evaluation of the machine and its use to examine resurfacing implants is presented.

Biomimetic materials are substances that replicate natural structures. There are several methods for producing such materials with highly developed surfaces from a wide range of polymers, but electrospinning is of particular interest due to its simplicity of implementation and the ability to modify the produced fibrous materials resembling structures found in living organisms. This study explores new biomimetic materials based on polyhydroxyalkanoates, specifically poly-3-hydroxybutyrate, modified with chlorophyll derivatives. The research investigates the impact of chlorophyll derivatives on the morphology, supramolecular structure, and key properties of nonwoven materials. The obtained results are of interest for the development of new biomimetic environmentally friendly materials for biomedicine with special properties.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

Rapid analysis and characterization of compounds by mass spectrometry may overlook trace compounds, although targeted analysis methods can significantly improve detection sensitivity, it is difficult to discover novel scaffold compounds. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathway. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methylanthranilate (MMA), fragmented in ESI-CID to produce rearrangement ion 3-hydroxyindole, which has been proven to exist in trace amounts in C. reticulata 'Chachi' comparing with the reference substance by LC-MS/MS. By combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA by purchasing or synthesizing reference substances and all of them were detected in C. reticulata 'Chachi' through LC-MS/MS analysis, achieving trace compound analysis from untargeted to targeted. It may contribute to explain the aging mechanism of C. reticulata 'Chachi' and the strategy of CID-induced special rearrangement ion binding metabolic pathway has potential application value in discovering trace compounds.

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial in mitigating oxidative stress in a hostile environment. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella abortus. In this study, to determine whether the inhibition of catalase can inhibit the intracellular growth of Brucella (B.) abortus, we employed 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, in both RAW 264.7 macrophage cells and an ICR mouse model during Brucella infection. The intracellular growth assay indicated that 3-AT exerts growth-inhibitory effects on B. abortus within macrophages. Aside from that, it contributes to the accumulation of reactive oxygen species and the formation of nitric oxide. Notably, 3-AT diminishes the activation of the nucleus transcription factor (NF-κB) and modulates cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced B. abortus proliferation within the spleen and liver of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by lowered levels of TNF-α, IL-6, IL-10, and altered CD4+/CD8+ T-cell ratio. These results suggest the protective and immunomodulatory effects of 3-AT treatment against Brucella infection.

Although multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in many neurological disabilities, optic neuritis (ON) is developed in some MS patients. However, the molecular mechanism of ON remains unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiology. We have previously shown that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), its animal model for human MS. In the current study, the expression of gal-3 was explored in the visual pathway of the EAE mice to clarify the pathogenesis of ON. Immunohistochemical analysis demonstrated that expression of gal-3 was increased in the visual pathway of the EAE mice during the peak disease, compared with naïve and EAE mice during the chronic disease. Expression of gal-3 was observed in mainly microglia/macrophages and astrocytes in the visual pathway of the EAE mice. In addition, gal-3+Iba-1+ cells with the phagocytic activities reflected by immunostaining with cathepsin-D were accumulated at demyelinating lesions in the visual pathway during peak disease of EAE. Moreover, NLRP3 expression was also detected in most gal-3+Iba-1+ cells. These results indicate a considerable possibility that gal-3 regulates the NLRP3 signaling in microglia/macrophages, followed by neuroinflammatory demyelination in ON. By contrast, astrocytic expression of gal-3 was also observed from the peak to the chronic disease. Taken together, the current study suggests a critical role of gal-3 in the pathogenesis of ON and proposes gal-3 in glial cells as a potential therapeutic target for ON.

In the context of evaluating physical function in individuals with stroke, the 3-meter backward walk test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test-retest reliability and construct validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) three times by different physiotherapists. Results indicated the 3MBWT displayed high reliability (r=0.97-0.98) and showed significant construct validity with other established walking tests like the 6MWT (r=-0.78) and 10MWT (r=0.71), with a moderate correlation to the FGA (r=-0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and validates well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.

This paper presents a) the novel hybrid learning method to train the type-1 non-singleton interval type-3 (IT3) fuzzy logic systems (IT3 NSFLS-1) and b) the novel method named enhanced Wagner-Hagras (EWH) IT3 NSFLS-1 fuzzy systems which includes the level alpha 0 output to calculate the output y alpha using the average of the outputs y alpha k instead of their weighted average. The development of the proposed methodology uses the orthogonal least square (OLS) method to train the consequent parameters and the back propagation (BP) method to train the antecedent parameters. This proposal dynamically changes the parameters of only the level alpha 0 minimizing some criterion function as new information becomes available to each level alpha k. The antecedent sets are type-2 fuzzy sets, the consequent sets are fuzzy centroids, the inputs are type-1 non-singleton fuzzy numbers with uncertain standard deviations, and the secondary membership functions are modeled as two Gaussians with uncertain standard deviation and the same mean. Based on the firing set of the level alpha 0, the proposed methodology calculates each firing set of each level alpha k to dynamically construct and update the EWH IT3 NSFLS-1 (OLS-BP) system. The algorithm was tested in a hot strip mill facility to predict the transfer bar surface temperature showing its superior capability to obtain the industrial pyrometer’s knowledge uncertainty for tuning and its better performance when compared with IT2 SFLS, IT2 NSFLS-1, GT2 SFLS, GT2 NSFLS-1, IT3 SFLS, and IT3 NSFLS-1 trained with the BP-BP algorithm.

In our previous published papers, considering 3 large atomic gravitational constants assumed to be associated with weak, strong and electromagnetic interactions, we have proposed the existence of a nuclear charge of magnitude, e_n=2.95e and developed a nuclear mass formula associated with strong and weak interactions having 4 simple terms and only one energy coefficient. Two important assumptions are, there exists a weak fermion of rest energy 585 GeV and strong coupling constant is the squared ratio of electromagnetic charge and nuclear charge. The aim of this paper is associated with understanding the mystery of quantum of magnetic flux, Planck’s quantum radiation constant and Reduced Planck’s constant. Proceeding further, quark charges, strong coupling constant, nuclear stability, nuclear binding energy, medium and heavy atomic X-ray levels and celestial magnetic moments can be understood in a unified approach. It may also be noted that, by considering integral nature of elementary particle masses, it seems possible to understand the discreteness of angular momentum. Considering our proposed e_n=2.95e=3e as a characteristic nuclear charge, it seems possible to understand the integral nature of quarks electromagnetic charge. With this idea, neutron, proton and pions decay can be understood very easily. In all the cases, up quark of charge (±2e) seems to play a crucial role with the internal transformation of down quark of charge (±e) and external observable elementary basic elementary particles. It needs further study at fundamental level.

Due to the growing interest in biopolymers, biosynthesizable and biodegradable polymers currently occupy a special place. Unfortunately, the properties of native biopolymers are not satisfactory, which explain that attempts are being made to modify them. The work attempts to improve the properties of poly(3-hydroxybutyrate) (P3HB) using linear aliphatic polyurethane (PU) based on 1,4-butanediol and hexamethylene 1,6-diisocyanate. The conducted studies on the effect of the amount of PU used (5, 10, 15 and 20 wt.%) showed an improvement in the thermal properties of the prepared polymer blends. There was an increase in the degradation temperature of the ob-tained blends in relation to the native P3HB by 12-57C, and the difference between the melting point and the degradation point was above 100°C for most of the obtained blends. As part of the tested mechanical properties of the new polymer blends, we noted the desired increase in the tensile strength, in the relative elongation at break and in the impact strength with a decrease in hardness, in particular with the presence of 5 wt.% PU. Therefore, for further improvement, hybrid nanobiocomposites with 5 wt.% PU and organically modified montmorillonite (MMT – Cloisite 30B) were produced. The nanoadditive was used in typical amount of 1-3 wt.%. The nanostructure of the biocomposites produced by extrusion was examined by small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), the morphology by scanning electron microscopy (SEM), and compatibility by infrared spectroscopy (FT IR). In addition, selected mechanical properties were determined and thermal properties were tested by the thermogravimetric analysis (TGA) and the standard differential scanning calorimetry (DSC). The polyester and polyurethane chains penetrated into the interlayer spaces of organically modi-fied nanoclay – Cloisite30B and the complete delamination occurred during direct mixing in the extrusion process. FT IR spectral analysis showed the compatibility of the polymer biocomposite components by the coexistence of intermolecular interactions in the form of hydrogen bonds. The morphology studies of the produced hybrid nanobiocomposites showed an interaction of the bi-opolymer matrix with PU and Cloisite30B and the formation of easily migrating polyester-polyurethane-montmorillonite adducts, which resulted in improved mechanical properties com-pared to the properties of the native P3HB and P3HB-PU compositions. The influence of the presence of a nanofiller on the properties of the prepared nanobiocomposites was tested and it was found that, as expected, the smallest amount of nanofiller provides the best results.It was found that the obtained nanobiocomposites containing the smallest amount of nano-fillers, i.e. 1 wt.% Cloisite30B exhibited the best mechanical and thermal properties. The desired decrease in hardness by 15% and a higher value of impact strength by 15%, an increase in elonga-tion at break by 60% and an increase in thermal stability of the newly produced biocomposites compared to to the native P3HB were observed. The prepared nanobiocomposites combined the best features caused by the elasticizing effect of polyurethane and the formation of P3HB-PU-MMT adducts.

Background: The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design: The RBAC-QoL study is a double-blind, randomised, controlled pilot feasibility study. The aim is to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes are the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods: Recruitment targets adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions are RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data is collected from five study visits six weeks apart. The trial is ongoing. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance is observed and adjusted with covariates. Results: Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F[1,8] = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (week 18) and total protein (weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions: RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway. These findings are preliminary but valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

This study investigates the therapeutic potential of new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of depression in 48 male Wistar rats was used a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group receiving saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to intact animals. These results suggest that Compound I has a reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis and better prognosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

The craft guilds have been at the core of important historiographical debates on the economic, social and political history of medieval cities for twenty years. The aim of this article is to examine the seamen’s guilds in the town ports of Northern Peninsula in the late Middle Ages. This study analyzes fundamental aspects of the social assistance, labour organization and social identity of the town ports, located on the maritime border of the Kingdom of Castile. In contrast to the more classical view of the craft guilds as protectionist institutions, which only served the interests of a privileged group of masters, this analysis highlights the contribution of the seamen craft guilds to the organization of labor at sea, the training of sea workers, the ability to negotiate with merchants and avoid labor exploitation, the provision of social assistance to the most vulnerable population, and the ability to lead the social protest for the guilders’ representation in the urban government. In summary, it is concluded that the seafarers’ guilds were constituted as networks of mutual help between individuals in the labor, welfare and political spheres of the population of the town ports of Northern Iberia in the late Middle Ages.

We review the main features of the non-local gauge, named the contour gauge. The contour gauge belongs to the axial type of gauges and extends the local gauge used in the most of approaches. The geometry of gluon fields and the path-dependent formalism are the essential tools for the description of non-local gauges. The principle feature of the contour gauge is that there are no the residual gauges which are left in the finite domain of space. In the review, we present the useful correspondence between the contour gauge conception and the Hamiltonian (Lagrangian) formalism. The Hamiltonian formalism is turned out to be a very convenient framework for the understanding of contour gauges. The comprehensive comparison analysis of the local and non-local gauges advocates the advantage of the contour gauge use. As an example of practical worth, we consider the Drell-Yan process and discuss the gauge invariance of the corresponding hadron tensor. We show that the appropriate use the contour gauge leads to the existence of extra diagram contributions. These additional contributions, first, restore the gauge invariance of the hadron tensor and, second, give the important terms for the observable quantities. We also demonstrate the significant role of the additional diagrams to form the relevant contour in the Wilson path-ordered exponential. Ultimately, it leads to the spurious singularity fixing. Moreover, in the present review, we discuss in detail the problem of spin and orbital angular momentum separation. We show that in SU(3) gauge theories the gluon decomposition on the physical and pure gauge components has a strong mathematical evidence provided the contour gauge conception has been used. In addition, we prove that the contour gauge possesses the special kind of residual gauge that manifests at the boundary of space. Besides, the boundary field configurations can be associated with the pure gauge fields.

Salmonid alphavirus strain 3 is responsible for outbreaks of pancreas disease in salmon and rainbow trout in Norway. Although the extensive amount of research on SAV3 focused mainly on the heart and pancreas (of clinical importance), tropism and pathogenesis studies of the virus in other salmon tissues are limited. Here, we used a combination of RT-qPCR (Q_nsp1 gene) and in situ hybridization (RNAscope®) to demonstrate the tropism of SAV3 in situ in tissues of Atlantic salmon, employing a challenge model (by cohabitation). In addition, as previous results suggested that pseudobranch may harbor the virus, the change in the expression of different immune genes upon SAV3 infection (RT-qPCR) was focused on the pseudobranch in the current study. In situ hybridization detected SAV3 in the heart, pseudobranch, gills, pyloric caeca, and pancreas after virus infection, with the heart ventricle showing the most extensive infection. Furthermore, the detection of the virus at different adipose tissues associated with the internal organs of the salmon, suggests a specific affinity of SAV3 to adipocyte’s components. The innate immune response to SAV3 in the pseudobranch after infection dominated over the adaptive responses, yet it did not mitigate the infection in that tissue. The early detection of SAV3 in the pseudobranch after infection, along with the persistent low infection over the experimental course, suggests a pivotal role of the pseudobranch in SAV3 pathogenesis in Atlantic salmon.

Natural products, especially biologically active compounds derived from plants, have been and continue to be invaluable in anticancer research and therapeutic discoveries. Rice bran arabinoxylan compound (RBAC) is a heteropolysaccharide extract of defatted rice bran obtained through enzymatic treatment with Lentinus Edodes mycelium. RBAC exhibited antitumour properties by arresting in vivo tumour growth in several murine models. In vitro experiments showed RBAC to promote apoptosis in cancer cells by increasing the susceptibility of CD95 (Fas/APO-1) ligands and downregulating Bcl-2 proteins to trigger the permeabilisation of the mitochondrial membrane. RBAC may restore immune dysfunction in cancer patients, most notably by upregulating natural killer cell activity and modulating cytokine production to enhance inflammatory and cytotoxic responses. As such, RBAC acts on the immune system to enhance chemopreventative activity and block tumourigenesis. In treatment, RBAC works synergistically with other natural products and chemotherapeutic agents, such as daunorubicin and paclitaxel, by enhancing drug transport to increase DNA damage in tumours and reduce proliferation. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence, and prolonged survival time. RBAC has been shown to augment the endogenous antioxidant system to prevent oxidative stress and thus protect against the harmful side effects of radiation therapy. RBAC also has chemoprotective effects, with animal and human studies showing reduced toxicity and side effects from chemotherapy, leading to improved health-related quality of life. Meta-analysing the best available evidence indicates that RBAC treatment increases the odds of survival among cancer patients by 4.02 times (95% CI: 1.67, 9.69) in the first year and 2.89 (95% CI: 1.56, 5.35) times in the second year after commencing treatment, compared to those not treated with RBAC. Notwithstanding, additional research is needed to characterise, quantify, and standardise the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to further substantiate the treatment efficacies.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS.Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm³. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume.Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS. Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm3. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

In this paper, we study the effect of parasitic channel on electrical characteristics and power consumptions of vertically stacked gate-all-around (GAA) silicon nanosheet (NS) MOSFETs of the bulk and silicon-on-insulator (SOI) substrates. Through deliberate control of the bottom parasitic channel coverage, we systematically assess its influence on DC, AC, and RF characteristics including power consumption. The observed findings highlight a significant differentiation among the bottom parasitic channels: GAA (i.e., control sample with 100% coverage), omega-shaped gate NS (70% and 80% coverages), and FinFET (60% coverage). Compared with the device with a 60% coverage channel, the device with a 100% coverage channel possesses 3520% and 8030% normalized leakage current improvement for both NFET and PFET under the bulk substrate, respectively. Compared with bulk-substrate devices, the SOI-substrate devices further significantly improve the leakage current. Due to enhanced off-state current leakages in the 100% covered bulk-substrate device, the static power demonstrates a notable improvement (about 98.1%), compared to 60% covered devices. Hence, the utilization of a 60% covered channel will result in a degradation of both device and circuit performance. The observation of GAA NS MOSFET indicates that an increase in the bottom parasitic channel coverage ratio leads to a positive impact on power consumption and leakage currents. The examination presented here is useful in the fabrication of stacked GAA NS MOSFETs.

Load shifting is one of the demand side management (DSM) strategies to support the efficiency in the electricity grid during the peak hours demand. Load shifting at the appliance level is interesting to review since the appliance usage is one of the main inputs in the load profile analysis. More review studies in load shifting at the appliance level are required as it is a specific issue of load profile research body, and still limited studies are available at this moment. It is also essential to focus on the appliance usage patterns to better understand the impacts and characteristics of the individual appliance. The existing studies in load shifting have applied common structured literature reviews, and our study addresses the transparency of each stage and sub-stage of the selection of the final list studies. The finding shows that efficiency has been achieved in the installed capacity reduction, cost including emission reductions, and peak consumption reduction. The most applied method in the load shifting at the appliance level is by developing the load shifting optimisation algorithms. This work contributes to provide a transparent process of applying a systematicity literature review, where it becomes a source of knowledge and grounded theory. It contributes to a limited and specific research of load shifting at the appliance level by highlighting and discussing the key findings for the readers. In specific, it contributes to improve energy efficiency by presenting the load shifting methods at the appliance level and identifying the controllable and uncontrollable appliances. This detail review study at the appliance level can make valuable contributions to support decision and policy-making by illuminating new dynamic system in load shifting area in specific, and demand side management in general for energy efficiency.

Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression. SRC-3 is a member of this family that interacts with, and enhances the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy. The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness. Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.

Background: Prostate cancer remains a significant global health concern, and understanding the molecular drivers of this disease is crucial for developing effective diagnostic and therapeutic strategies. Steroid Receptor Coactivator-3 (SRC-3), a member of the SRC family, has emerged as a key player in prostate cancer pathogenesis. This review comprehensively examine the role of SRC-3 in prostate cancer, encompassing molecular mechanisms, clinical implications, and therapeutic opportunities. Methods: A systematic literature search following PRISMA guidelines was conducted in PubMed, PMC, and other relevant databases to identify studies that investigate SRC-3 in prostate cancer. A total of 67 articles were selected based on predetermined inclusion criteria. Results: 785 articles were retrieved from databases using specific keywords and MeSH terms related to SRC-3 and Prostate Cancer. After removing 461 duplicates, 260 articles were excluded based on title and abstract review. Subsequently, a comprehensive screening by three researchers resulted in 47 relevant articles for this systematic review. We summarize its contributions to AR-mediated transcriptional regulation, tumor growth, and metastasis. Evidence suggests that SRC-3 expression correlates with prostate cancer aggressiveness, disease recurrence, and poor patient outcomes. Its potential as a diagnostic biomarker and therapeutic target is explored, offering insights into personalized medicine approaches. Conclusions: SRC-3 plays a pivotal role in prostate cancer, influencing disease progression and clinical outcomes. Understanding the molecular intricacies of SRC-3 in prostate cancer offers new opportunities for precision medicine and innovative therapeutic approaches. This review provides a comprehensive overview of SRC-3's involvement in prostate cancer, emphasizing its clinical relevance and potential as a therapeutic target, ultimately contributing to improved patient care in the era of personalized oncology.

Background Candida auris is an emerging multidrug-resistant fungal pathogen that represents a serious threat to healthcare settings currently. Objective: Its objective was to determine the prevalence of C. auris in the hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts. and medical files of all suspected? and confirmed cases of C. auris cases reported at King Khalid University Hospital, Riyadh between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infection in our facility. We established our initial prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed cases positive for C. auris during the study period, 33 (62%) were males. Their ages ranged between 15 and 98; most positive cases occurred in 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and Urine samples yielded the greatest number of positive cases while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence could serve as our baseline/benchmark to compare with regional and international benchmarks.

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.

The patient was a 44-year-old woman with suspected Stevens-Johnson syndrome due to Baktar® (sulfamethoxazole trimethoprim) medication received at our outpatient dermatology clinic. Histopathological examination of the epidermis, dermis, and subcutaneous adipose tissue samples showed numerous necrotic keratinocytes in the epidermis. Apoptotic nuclei were visualized as diaminobenzidine brown deposits with immunoperoxidase staining for cleaved caspase-3. Cleaved-caspase3-positive findings were consistent with eosinophilic material that appeared to be necrotic cells within the epidermis. Therefore, these eosinophilic materials must be apoptotic bodies. Generally speaking, and especially in Japan, these materials are considered necrotic keratinocytes. To our best knowledge, no studies have used apoptotic immunohistochemical markers to examine whether these structures are apoptotic.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.