Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

KLFs seem to associate with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of differentiation of cardiac myofibroblasts or a modified fatty acid oxidation, related to the formation of a dilated cardiomyopathy; myocardial infarctions, left ventricular hypertrophy and diabetic cardiomyopathies. MicroRNA have been involved in certain regulatory loops of KLFs as they may function as critical modulators of vascular smooth muscle cells in atherosclerosis, in heart failure and as markers of endothelial damage in acute myocardial infarction.

Cardiac hypertrophy typically follows myocardial damage, a process known to involve members of the Krüppel-Like Factors (KLFs) which have pro-hypertrophic and anti-hypertrophic roles. Our study delved into the molecular mechanisms underlying KLFs-cardiac hypertrophy interplay post myocardial infraction. We induced myocardial dam-age in rats using isoproterenol. Total RNA was extracted from the left ventricle and Quantitative Real Time RT-PCR was conducted to assess the expression of KLFs, cardiac commitment genes, inflammatory markers, and certain conduction-related genes. We devel-oped a computational approach to construct a proteomic network centered on KLFs. Initial results revealed early expression (2-3 days post-induction) of KLF3, KLF4 and KLF6, followed by the subsequent expression of KLF11 and KLF15 (5-8 days after induction). In the maturation stage, KLF12 and KLF13 regulators were found upregulated. IL-6 was gradually found to be upregulated through. Interaction analysis revealed KLF3, KLF8 and KLF12 interacted with cardiac electrical functions. RT-PCR confirmed up-regulation in cardiac genes linked to electrical function and scar maturation. Our findings underscore the central role of KLFs during the modulation of the cardiac hypertrophic response. Dysregulation of KLF expression resulted in damaged myocardium, participating in the progression of abnormal hypertrophy, highlighting their potential as therapeutic targets for heart diseases.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Background: Myocardial infarction is increasing at a young age. New tools are needed to evaluate the risk population of young patients. GDF-15 has been implicated in several key mechanisms of atherogenesis and also is associated with increased mortality and cardiovascular events in patients with coronary artery disease. Arterial stiffness parameters, including pulse wave velocity, can also be measured using peripheral arterial tonometry and can indicate the presence or progression of atherosclerotic changes. The aim of this study is to evaluate the GDF-15 level and arterial stiffness parameters in patients with premature myocardial infarction Method: Thirty patients who recovered from a myocardial infarction were consecutively included. Fifteen age-sex-matched subjects were included as controls. The patients’ serum GDF-15 concentration levels were measured using relevant kits. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were performed using a Mobil-O-Graph arteriography system. Results: GDF-15 concentration levels were significantly higher in the patients with premature myocardial infarction when compared to controls. PWV and AIx were similar between the groups. GDF-15 level was negatively correlated with high-density cholesterol (HDL) and positively correlated with uric acid levels in all study populations. Conclusions: GDF-15 levels may be a risk factor for patients with premature myocardial infarction. This pilot study may trigger further studies to elucidate the central role of GDF-15 in the pathophysiology of early atherosclerosis in the young population.

Background: Since cytokine receptor like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. Methods: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno associated virus (AAV) or AAV containing CRLF1 was determined by morpholog-ical, histological and microCT analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were deter-mined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes us-ing real time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Results: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondro-genic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and Cardiotrophin like Cytokine (CLC) stimulated catabolic events via STAT3 activation. Conclusion: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

This paper presents laboratory devices on which experimental measurements were carried out to prove the validity of the assumption about the reduction of vibrations transmitted to the conveyor belt structure generated by the impact forces of falling material grains in the places of transfer or on the hoppers of conveyor belts. In order to limit damage to the conveyor belts caused by the impact of the sharp edges of material grains, conveyor belts are supported by impact rollers or impact rubber rods in the places of transfers and on the hoppers of belt conveyors. The flattened ends of the impact rollers are inserted into the grooves of steel brackets installed on the supports of the fixed conveyor idlers of a conventional design. In this paper, a special modification of the fixed conveyor idler is presented, which consists of inserting plastic brackets into the structurally modified roller axle holders of the fixed conveyor idler. Measurements were carried out on the first laboratory device, which showed that the specially modified fixed conveyor idler resulted in a higher damping of up to 15% of the impact forces of the falling weight on the rubberized hoop of the impact roller shell compared to the conventional fixed conveyor idler design. Measurements carried out on the second laboratory device show that the effective vibration velocity values detected at the points where the impact roller axis fits into the fixed roller table holder, i.e. points B and D, are higher than when using plastic brackets, up to 6% for a 108 mm diameter roller, compared to steel impact roller brackets.

In mining machines with friction discs, but also in multi-rope traction elevators, it is necessary to distribute the applied tensile load, generated by the weight of the cage and counterweight, evenly in all cross-sections of the load-bearing ropes. Hydraulic devices used for this purpose can operate on the principle of Pascal's law. The article presents a structural design, a 3D model and an implemented solution of a laboratory device capable of simulating a practical method of evenly distributing the total weight of the load into partial tensile forces of the same size acting on a selected number of load-bearing ropes. The laboratory equipment uses two pairs of three steel cables of finite length for the simulations. During the experimental measurements, tensile forces derived from the tractive force of the piston rods, pushed into the bodies of the hydraulic cylinders by the pressure of the hydraulic oil supplied through the pipeline under the pistons of the hydraulic cylinders, were detected. The resulting amount of hydraulic oil pressure in the hydraulic circuit influenced by different values of the hydraulic oil pressures in the hydraulic cylinders and by the pressure in the supply pipe was experimentally studied on the laboratory equipment. Simulations were also carried out in order to detect the hydraulic oil pressure in the hydraulic circuit caused by the change in the different magnitudes of the tensile forces in the ropes From the experiments carried out, it follows that with the appropriate choice of hydraulic elements and the design of the hydraulic circuit, the weight of the load, acting as the total pulling force in the ropes, can be evenly distributed (with a deviation of up to 5%) to all cross-sections of the load-bearing ropes. If the exact values of the hydraulic oil volumes under the pistons of all hydraulic cylinders are not known, it is not possible to calculate the pressure values in the hydraulic circuit when the valves of the hydraulic pipes are gradually opened.

The article focuses on mining of non-energy mineral resources with minimum environmental impacts. It issues from research results of a project Competence Centre for Effective and Ecological Mining of Mineral Resources implemented at the Faculty of Mining and Geology at VŠB-Technical University of Ostrava, Czech Geological Survey, a company Watrad ltd., a state enterprise Diamo, a company RPS Ostrava plc and a company Sedlecký kaolin plc. The paper starts with a partial analysis of the existing legal norms related to mining and processing of mineral resources. Next, it analyses mineral resource mining options free of negative environmental impacts. The fundamental tool to assess potential environmental impacts of mining is the implementation of Environmental Impact Assessment (EIA) process for a given mineral resource. In the Czech Republic environmental impact assessment is carried out by course of Act 100/2001 Coll. Its important amendment is Act 39/2015 Coll. claiming, inter alia, that the environmental impact assessment is rigidly connected with other permits and procedures, such as the zoning process and building construction permits. The article describes the environmental impacts of mining of non-energy mineral resources, including the following factors: appropriation of land, impacts on surface water, ground water and soil, noise, influence on the landscape character, and air pollution. The paper also includes a case study summarizing information on the environmental factors that may play a role in potential underground mining of graphite in the deposit Český Krumlov - Městský Vrch and the deposit Lazec - Křenov.

Tissue-like phantoms are widely used as a model for mimicking the optical properties of live tissue. This paper presents the results of a diffusion reflection method as well as fluorescence lifetime imaging microscopy measurements of fluorescein-conjugated gold nanorods in solution as well as inserted in solid tissue-imitating phantoms. A lack of consistency between the fluorescence lifetime results of the solutions and the phantoms raises a question about the ability of tissue-like phantoms to maintain the optical properties of inserted contrast agents.

Mammals have two insulin-like growth factors (IGF) that are key mediators of somatic growth, of tissue differentiation and cellular responses to stress. Thus, the mechanisms that regulate the bioavailability of IGFs are important in both normal and aberrant development. IGF-I levels are primarily controlled via the growth hormone-IGF axis, in response to nutritional status, and also reflect metabolic diseases and cancer. One mechanism that controls IGF bioavailablity is the binding of circulating IGF to a number of binding proteins that keep IGF in a stable, but receptor non-binding state. But even before IGF is released from the cells that produce it, it undergoes an obligatory association with a ubiquitous chaperone protein, GRP94. This binding is required for secretion of a properly folded, mature IGF. This chapter reviews the known aspects of the interaction and highlights the specificity issues yet to be determined. The IGF-GRP94 interaction provides a potential novel mechanism of idiopathic short stature, involving the obligatory chaperone and not just IGF gene expression. It also provides a novel target for cancer treatment, as GRP94 activity can be either inhibited or enhanced.

Abstract: Brassinosteroids (BR) are essential plant hormones that play a crucial role in regulating plant growth and development, as well as their resistance to abiotic and biotic stresses, including pathogen infections. In the context of plant im-munity, BR influence various processes such as the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the re-inforcement of the plant cell structure. The aim of work is understand the role of BR in plant defense against abiotic and biotic stresses. BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, contributing to increased plant resistance to abiotic stresses. The study discusses various mechanisms of BR action on plant immunity, including the regulation of gene expression related to defense, activation of the plant defense system, in-teraction with other plant hormones, regulation of water and salt balance, and influence on photosynthetic processes. In the context of plant immunity, BR influence various processes, including the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the reinforcement of the plant cell structure. Additionally, BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, con-tributing to increased plant resistance to abiotic and biotic stresses. The paper emphasizes the importance of further research on the role and mechanisms of action of BR in plant immunity, which may contribute to the development of more effective strategies for the use of BR in agriculture, horticulture, and plant protection.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

According to some authors, the serum selenium level is strongly associated with the severity of liver diseases including liver cirrhosis. The aim of the study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines – interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in serum of 99 alcoholic liver cirrhosis patients divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among different pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TB), and Xiangcun black (XB) piglets (20 piglets per breed) were selected at 21 and 24 days of age (three days of post-weaning) to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF system-related components in different tissues. The plasma IGFBP-3 level in TB piglets was higher (P > 0.05) than in the XB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (P < 0.05) in the kidney but was higher (P < 0.05) in the spleen of XB and TB piglets. At 24 days of age, the IGF-1 expression was higher (P < 0.05) in the kidney of TB piglets than in the XB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XB and TB piglets were lower (P < 0.05) compared with the DR piglets. Weaning down-regulated (P < 0.05) the IGF-1 expression in the jejunum, spleen, and liver of piglets, while up-regulated (P < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman’s correlation analysis showed a negative correlation (P < 0.05) between plasma IGFBP-2 and IGFBP-5 and the organ index of piglets. Collectively, there were significant differences in IGF system components among different pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

Molecular analysis is an easier means to identify and isolate a specific gene which has imperative function for growth, body composition , fat deposition, metabolic and skeletal traits as well as the molecular genetics selection on individual genes is a very efficient method to genetically improve economically important traits in chickens. Insulin- like growth factor 1 ( IGF-1)is a member of a heterogeneous group of peptides with important growth.Transforming growth factorβ ( TGF-β) belongs to a large family of growth and differentiation factors that play a pivotal role in a great variety of biological activities including morphogenesis, development and differentiation. DNA was extracted from 48 chickens sampled from three strains Lohman (17) , Sinai (24) and Gimmizah (7) IGF-1 gene and TGFβ2 gene were amplified using PCR protocol. Electrophoresis was carried out on the products of PCR , bands viewed on transilluminator. The size of IGF-1 gene was 675 bp while the size of TGFβ2 gene was 188bp. Sharp bands were purified and sequenced and used the dendrogram to show the relationships between other vertebrate species

The 2-Acetyl-1-pyrroline (2-AP) is the most important volatile in determining the aroma of fragrant rice, however, the transcriptional regulation mechanism of 2-AP biosynthesis in fragrant rice is still unclear. In this study, the Osp5cs1 knockout mutant lines and OsP5CS1 over-expression lines were constructed by genetic transformation of indica rice cultivar i.e., ‘Zhonghua11’, which was knocked out OsBADH2 to produce fragrance in aromatic rice. The OsP5CS1 gene was also identified as a key gene in the 2-AP biosynthesis pathway of aromatic rice. The OsP5CS1 promoter was used as bait, and the transcription factor OsbZIP60-like was screened by yeast one-hybrid assays. The transcription factor OsbZIP60-like specifically bound to the OsP5CS1 gene. The dual luciferase reporting system found that OsbZIP60-like transcription factor promoted the transcriptional activation of OsP5CS1. Compared with the wild type, the OsP5CS1 gene expression was significantly down-regulated in Osbzip60-like mutant, and resulted in substantial reduction in 2-AP biosynthesis. Moreover, the OsP5CS1 gene expression was significantly up-regulated in OsbZIP60-like over-expressed plants, and the 2-AP concentrations were also increased whereas the Osbzip60-like mutants were found to be sensitive to Zn deficiency. Overall, the OsbZIP60-like transcription factor promoted the 2-AP accumulation. This study provides a theoretical basis for the transcriptional regulation mechanism of 2-AP biosynthesis and explores the function of OsbZIP transcription factor in fragrant rice.

The removal of sulfur from fossil fuels is one of the most important processes in modern refineries. It is accomplished via hydrodesulfurization (HDS) of the sulfur organic compounds in presence of heterogeneous catalysts. In the current work, heterogeneous catalysts containing cobalt and mo-lybdenum supported on mesoporous materials type SBA-15 and AlSBA-15 were synthesized for application in the HDS reactions of thiophene in n-heptane stream. The mesoporous materials were synthesized by hydrothermal method starting from TEOS, pseudobohemite, hydrochloric ac-id and water. Pluronic P123 was used as template. The best calcination conditions for removal of the organic template were optimized by thermogravimetry analysis (TG/DTG). The calcined SBA-15 and AlSBA-15 supports were submitted to co-impregnation with solutions of cobalt nitrate and ammonium heptamolybdate, aiming the production of 15% in mass of metal loading with atomic ratio of [Co/(Co+Mo)]=0.45. The obtained materials were dried and calcined for obtaining the mesoporous catalysts in the form of CoMo/SBA-15 and CoMo/AlSBA-15. The catalysts were char-acterized by XRD, TG/DTG, SEM and nitrogen adsorption. From XRD analysis, it was verified that after decomposition of the cobalt and molybdenun salts, were formed MoO3, Co3O4 and Co-MoO4 oxides on the supports, being attributed to these chemical species the activity for the HDS reactions. The activity of the obtained catalysts was evaluated in a continuously flowing tubular fixed-bed microreactor coupled on-line to a gas chromatograph, using n-heptane stream contain-ing 12070 ppm of thiophene (ca. 5100 ppm of sulfur) as a model compound. From the catalytic tests it was verified that the synthesized catalysts presented good activity for the reaction, and the main obtained products were cis- and trans-2-butene, 1-butene, n-butane and low amounts of iso-butane. The presence of 1,3-butadiene and tetrahydrothiophene (THT) were not detected. A mechanism of the primary and secondary reactions and subsequent formation of the olefins and paraffins, in the CoMo/SBA-15 and CoMo/AlSBA-15 mesoporous catalysts were proposed, con-sidering steps of desulfurization, hydrogenation, dehydrogenation, THT decyclization and isomerization.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

Waste glycerol can be subjected to various processing operations, including purification and re-fining, to obtain glycerol of appropriate purity. In addition, alternative methods of utilising waste glycerol are also being sought, e.g. by converting it into other valuable chemical products or biofuels. Therefore, various technologies are being developed to utilise this type of waste effectively and sustainably. The production of value-added products from waste glycerol is an important issue that determines the improvement of the economic viability of biofuel production and corresponds to the model of a waste-free and emission-free circular economy. This paper characterised the mechanisms and evaluated the efficiency of existing methods of microbiological utilisation of waste glycerol into liquid biofuels, including biodiesel, bioethanol and biobutanol, and identified further directions for the production of value-added products. In addition, a bibliographical analysis of publications re-lated to the production of liquid fuels and economically valuable products from glycerol was carried out, the progress of research and application work was assessed and directions for future research were identified.

Dominance hierarchies are ubiquitous in invertebrates and vertebrates, but little is known on how genes influence dominance rank. Our gaps in knowledge are specifically significant concerning female hierarchies and in insects. To start filling these gaps we studied the social bumble bee Bombus terrestris, in which social hierarchies among females are common and functionally significant. Dominance rank in this bee is influenced by multiple factors, including juvenile hormone (JH) that is a major gonadotropin in this species. We tested the hypothesis that the JH responsive transcription factor Krüppel homologue 1 (Kr-h1) mediates hormonal influence on dominance behavior in the bumble bee. We first developed and validated a perfluorocarbon nanoparticles-based RNA interference protocol for knocking down Kr-h1 expression. We then used this procedure to show that Kr-h1 mediates the influence of JH not only on oogenesis and wax production, but also on aggression and dominance rank. To the best of our knowledge, this is the first study causally linking a gene to dominance rank in social insects, and one of only a few such studies in insects or in female hierarchies. These findings are important for determining whether there are general molecular principles governing dominance rank across gender and taxa.

The aim of this work is research dedicated to the search for new bactericidal systems for use in cosmetic formulations, dermocosmetics, or the production of wound dressings. Over the last two decades chitosan due to its special biological activity, has become a highly indispensable biopolymer with very wide application possibilities. Literature reports on the antibacterial effects of chitosan are very diverse, but our research has shown that they can be successfully improved through chemical modification. Therefore, in this study, results on the synthesis of new Schiff bases chitosan – dCsSB-SFD and dCsSB-PCA obtained using two aldehydes: sodium 4-formylbenzene-1,3-disulfonate (SFD) and 2-pyridine carboxaldehyde (PCA) respectively. Chitosan derivatives synthesized in this way demonstrate stronger antimicrobial activity. Carrying out the procedure of grafting chitosan with a caproyl chain allowed obtaining compatible blends of chitosan derivatives with κ-carrageenan, which are stable hydrogels with a high swelling coefficient. Furthermore, covalently bounded PCL improved the solubility of obtained polymers in organic solvents. With this respect, the Schiff base-containing polymers obtained in this study, with special hydrogel and antimicrobial properties are very promising materials for the potential use as a controlled-release formulation of both, hydrophilic and hydrophobic drugs in cosmetic products for skin health.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

It was the aim of this study to examine whether the usage of the vaccine COXEVAC® (Ceva Santé Animale) could reduce the consumption of antibiotics in Q-fever-positive dairy farms. Additionally, the effects of other herd-level factors on the consumption of antibiotics were investigated. In this longitudinal cohort study, 36 farms with vaccination and 13 farms without vaccination participated. In all herds, Coxiella burnetii had been directly or indirectly diagnosed. To compare the treatment frequency of antibiotics between the vaccinated group and the non-vaccinated group, the consumption of antibiotics for each farm was collected using the veterinary documents about the application and delivery of antibiotics. To gather detailed information about herd data, nutrition, milking management, housing, and animal health, the farmers were interviewed with the help of a questionnaire. The results suggest that there might be an association between the vaccination against Q fever and a reduced consumption of antibiotics. Neither herd size nor milk yield level influenced the consumption of antibiotics in the study herds. Type of flooring and udder cluster disinfection while milking were associated with a lower and higher therapy frequency, respectively. Further studies are necessary to elucidate the cause-effect relationship between vaccination and the consumption of antibiotics.

In the current study, a two-dimensional numerical study is carried out to investigate the performance of a novel Double-chamber Parallel Flexible Valves micropump, which utilized the electrowetting-on-dielectrics (EWOD) effect to drive the microfluid flow. By observing the flow fields, the internal circulations are seen on both the left and right side of the pump. The generation of the backflow is discussed by tracking the movement of the vortices. Only slight flow fluctuation is seen in the micropump. Based on the simulation outcomes, the structural parameters including the width of the inlet/outlet, the width of the pumping channel and the diverging angle in the micropump are analyzed, the influence of these parameters on the pumping volume and the maximum pressure have been discussed. Eventually, a group of optimal parameter combinations is given according to the results to extend the operating potential of the micropump.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

High-precision conical threads are widely used in responsible joints in the drilling of oil and gas wells. Difficult underground drilling conditions due to the occurrence of significant mechanical loads and an aggressive environment in wells require the use of workable materials that are often difficult to machine. The huge need for such connections dictates the use of high-performance cutting tools, which means that high demands are placed on their effective geometric performance. The study describes the theoretical dependence of the profile precision of the tapered drill-string tool-joint threads of all standard sizes on the complex of a cutting tool geometric parameters and cutting tool setting accuracy. The experiments include an assessment of the geometric accuracy of the profile of the obtained NC23 thread connector, depending on the values of the installation angles and the declared tangential displacement of the standard threaded carbide insert.

Hyperlipidemia is an identified risk factor for metabolic syndrome, obesity and cardiovascular complications characterized by elevated levels of lipids in blood. The present study aimed to inhibit HMG-CoA reductase with 15-oxoursolic acid through in-vivo and in-silico assessments. HFD-induced hyperlipidemia in rats was developed with a marked increase in total cholesterol (58.34 ± 0.21 mg/dl), triglycerides (45.45 ± 0.39 mg/dl), LDL-c (66.12 ± 0.10 mg/dl), VLDL-c (19.34 ± 0.16 mg/dl), and a decrease in HDL-c (10.34 ± 0.18 mg/dl). The oral administration of 15-oxoursolic acid at a concentration of 30 mg/Kg b.w significantly reduced the serum concentration of total cholesterol (42.65 ± 0.54 mg/dl), triglycerides (32.33 ± 0.16 mg/dl), LDL-c (50.34 ± 0.15 mg/dl) and VLDL-c (13.15 ± 0.45 mg/dl) respectively and an increased in the serum HDL-c (18.56 ± 0.34 mg/dl). 15-oxo ursolic acid also caused a decrease in the coronary risk index and atherogenic risk index. In-silico studies of 15-oxoursolic acid with HMG-CoA reductase showed significant interaction capability with binding energy (-9.26805 Kcal/mol). It is concluded that 15-oxoursolic acid could significantly reduce the total cholesterol, triglycerides and LDL levels in HFD-induced hyperlipidemia rats which might lead to new medication with significant hypolipidemic potential.

This study explored the effects of cryogenic treatment on the microstructure, hardness, and wear-resistance of diamond-like carbon (DLC) by cryogenically treating NAK 80 mold steel coated with DLC. Raman spectroscopy analyzed the structure of the DLC film. Nanoindenter analyzed the hardness and Young’s modulus of the film, and their relationship determined the wear resistance. Wear test assessed the wear rate and friction coefficient of the DLC film. The results showed that cryogenic treatment increased the rate of carbide precipitation and refined the grain structure. Raman spectroscopy indicated that the Raman intensity rate (I_D/I_G) of treated DLC films was smaller than those without cryogenic treatment. When the sp3 bond increased, the hardness and wear-resistance of the DLC film also increased.

Insulin-like growth factor binding proteins (IGFBPs) are critical modulators of the metabolism. In adults, IGFBPs are associated with obesity and insulin resistance but the association of IGFBPs with metabolic homeostasis in children and adolescents is not fully characterized. In this study we investigated the association of plasma IGFBPs (IGFBP-1, 3 and 7) with weight status, central adiposity and cardiovascular disease markers Hs-CRP and Ox-LDL. A total of 420 adolescents (age 11-14 years) were randomly recruited from public middle schools in Kuwait. IGFBPs were measured using bead-based multiplexing while Hs-CRP and Ox-LDL were measured using ELISA. IGFBP-1 levels were significantly lower in obese and overweight participants compared to normal weight children. Only IGFBP-1 was negatively associated with waist circumference to height (WC/Ht) ratio. IGFBP-1 was negatively correlated with Hs-CRP while IGFBP-3 and IGFBP-7 were negatively correlated with Ox-LDL. These data demonstrate a robust negative association of IGFBP-1, but not IGFBP-3 or -7, with overweight and obesity, and the inflammation marker Hs-CRP. Central adiposity (WC/Ht ratio) was a stronger predictor of IGFBP-1 than BMI-for-age z-score. IGFBP-1 could thus be used as a sensitive predictive diagnostic tool for obesity and its subsequent effects in screening and monitoring of obesity-related metabolic complications in adolescents.

Every finite simple group P can be generated by two of its elements. Pairs of generators forP are available in the Atlas of finite group representations as (not necessarily minimal) permutation representations P . It is unusual but significant to recognize that a P is a Grothendieck’s dessin d’enfant D and that a wealth of standard graphs and finite geometries G - such as near polygons and their generalizations - are stabilized by a D. In our paper, tripods P − D − G of rank larger than two,corresponding to simple groups, are organized into classes, e.g. symplectic, unitary, sporadic, etc (as in the Atlas). An exhaustive search and characterization of non-trivial point-line configurationsdefined from small index representations of simple groups is performed, with the goal to recognize their quantum physical significance. All the defined geometries G's have a contextuality parameterclose to its maximal value 1.

Macrophages as a source and target of GDF-15

The aim of this work is to compare two softwares (MAUD and TOPAS) based on the Rietveld algorithm and to test the concept of tolerance factor using the dissolution at high temperature of yttrium into BaTiO₃. In general, both softwares give up different values of the crystalline parameters however the trends are similar in most cases but the analysis of the strain and crystallite size in the BaTiO₃ crystals suggests that, in this particular case, MAUD offered results more consistent with the expected behavior. Using the crystalline parameters calculated by Rietveld, the tolerance factor values were obtained and these data suggest even better stability in the crystalline structure than that expected using theoretical parameters. Tolerance factor concept also indicates that Ti⁴⁺ should be preferred.

The accumulation of brown algae from the genus Sargassum has been increasing over the years in coastal regions of the Caribbean, Africa, Brazil, and Mexico. This causes harmful effects to the ecosystem, health, economy, and climate due to gas emissions from its decomposition process. There is the possibility of this biomass being reused in civil construction, and few studies have been carried out on its application to common Portland cement mortar. As such, the objective of this study is to evaluate the potential of sargassum ash as a mineral addition to partial replacement of fine aggregates in Portland cement mortar. Characterizations of the raw materials were carried out through X-ray fluorescence spectroscopy, loss on ignition, particle size distribution, Brunauer–Emmett–Teller (BET), real density, X-ray diffraction, scanning electron microscopy, and dispersion spectroscopy of electrons. The mortars were prepared by partially replacing the fine aggregate (sand) with sargassum ash, at 0%, 5%, 10% and 20%. Mortar performance was evaluated through water absorption, apparent porosity, apparent specific mass, compressive strength after 7, 28, and 63 days after curing. Lastly, a life cycle assessment in accordance with ISO standards 14040:2006 and 14044:2006. The results showed that replacing sand with sargassum ash increases water absorption, apparent porosity, and decreases the apparent specific mass and compressive strength as replacement increases. Nevertheless, the compressive strength results after 63 days, for 5 and 10% replacement did not differ statistically from reference values. The life cycle assessment indicates that mortars with partial replacement of sand by sargassum ash showed positive environmental impacts when compared to reference values for most categories regardless of the scenario analyzed, especially for mortar with 10% replacement. As such, the use of sargassum ash at 10% does not alter compressive strength values after 63 days while reducing its environmental impact. The application of this biomass in civil construction materials provides a destination for this algae that has been causing several social, environmental, and economic problems.

This study investigates the mean annual water temperature trends at the confluence of the Sava and Danube Rivers, along with air temperature trends at the Belgrade meteorological station, spanning from 1956 to 2020. Results reveal a consistent increase in temperature across all three measuring stations, with the Danube experiencing a rise of 0.34°C/10 years, the Sava at 0.44°C/10 years, and Belgrade's air temperature increasing by 0.39°C/10 years. Employing the RAPS method, sharp rises in water temperature were pinpointed in 1989 for the Sava and 1990 for the Danube, while Belgrade's air temperature surge began in 1998. The highest intensity of air temperature increase within the recent period (1998-2020) was observed at the Belgrade observatory, reaching 0.76°C/10 years. Notably, the Sava exhibited a faster increase in water temperature over the last thirty years compared to the Danube. August marked the peak average water temperature for both rivers, while July recorded the highest average air temperature in Belgrade. Despite differing flow rates, both rivers exhibit similar hydrological regimes, with maximum flows occurring in April and minimum flows in August for the Sava, and October for the Danube. Seasonal temperature increases were most pronounced in summer, notably in August, with the smallest rises occurring during cold periods. Additionally, an inverse proportional relationship between mean annual water temperatures and discharges was observed at both river stations.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

We introduce two symmetric concepts to physics: “distance” (space and time in one) and “wavematter” (electromagnetic wave packet and matter in one). We claim that physics has chosen the wrong concept of time: It is not aware that the time of a moving object flows in a direction other than my time. We provide 15 proofs for our claim by solving 15 mysteries of physics graphically! For example, we prove that length contraction and time dilation are actually geometrical effects in a 4D manifold that we call “Euclidean spacetime” (ES). We prove that the discrepancy in calculating the Hubble constant stems from a systematic error in the redshift measurement. We prove that what I deem wave, deems itself matter, which solves wave–particle duality. We even untangle quantum entanglement without the issue of non-locality. We finally understand why alternative theories of Euclidean relativity have failed: They are all based on four dimensions of space rather than distance. A huge amount of energy was injected into ES at a point that we take as origin. Ever since has this energy been moving radially away at the speed of light. We live in the 3D hypersurface of an expanding 4D hypersphere. Hyperspherical coordinates have the great advantage that they reduce all that is ever happening to just one formula. So, it is the Theory of Everything in these coordinates: “Energy is covering radial distance which, divided by Euclidean time, is equal to the speed of light.” Acceleration and force like gravitation emerge from a rotation of objects in ES and a subsequent projection to 3D space. Matching the symmetry simplifies physics.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Suicide is a public health problem influenced by a variety of biological, psychological, social, and environmental factors. Recognizing the warning signs at each stage is crucial for prevention and helping those at risk. In this context, body awareness, especially interoceptive body awareness, emerges as a potentially relevant and underexplored factor. In this study, binary logistic regression and linear regression analyses were used to examine the relationship between interoceptive body awareness and suicidal orientation in Colombian university students. In addition, the bootstrap technique was used to resample and estimate the distribution of the data. The results support the idea that greater interoceptive awareness may protect against suicidal orientation by improving emotional regulation. An inverse relationship was found between interoceptive awareness and suicidal ideation. These findings are consistent with previous literature on the importance of body awareness for emotional well-being. Further longitudinal research is needed to explore this relationship in depth.

Nowadays, animal breeders look for effective innovations to care animal health. Use of probiotics, postbiotics, parabiotics and the other beneficial natural substances are dominated. Mundticin-like substance EM 41/3 is thermo-stable bacteriocin (postbiotic) with a broad antimicrobial spectrum. In this study its effect in broiler rabbits was assessed. Rabbits represent food-derived animal and they are also suitable animal model. The parameters tested were analyzed by validated methods. Administration of MLS EM 41/3 produced by non-autochthonous strain Enterococcus mundtii EM 41/3 lead to significant increase of parameter immunity-phagocytic activity, while it did not influence microbiota composition. It also did not influence blood biochemistry and no oxidative stress was noted. Moreover, higher growth parameters were noted and also stimulated hydrolytic activity. Finally, no negative influence on rabbit meat quality was noted. Postbiotic MLS EM 41/3 administration in feeding strategy seems to be contributing fact for rabbit health status maintaining.

Background: Fiber-reinforced composites (FRCs) have been proposed as an alternative to traditional metal alloys for the realization of frameworks in full-arch implant supported prostheses. The aim of the present in vitro study was to evaluate the deflection under load of seven prostheses endowed with frameworks made of different materials, including different types of fiber reinforced composites (FRCs). Methods: A master cast with four implant analogues in correspondence of the two lateral incisors and the two first molars was used to create full-arch fixed prostheses with the same shape and different materials. Prostheses were made in different materials (framework+veneering material): gold alloy+resin (Au+R), titanium+resin (Ti+R), FRC with multi-directional carbon fibers+resin (ICFRC+R), FRC with unidirectional carbon fibers+composite (UCFRC+C), FRC with glass fibers+resin (GFRC+R), FRC with glass fibers+composite (GFRC+C), resin (R, full-acrylic prosthesis). Flexural tests were conducted using Zwick/Roell Z 0.5 machine and the deflection of the lower surface of the prosthesis was measured in order to obtain load/deflection graphs. Results: Greater rigidity and less deflection were recorded for UCFRC+C, GFRC+C, followed by Ti+R, and Au+R. The greatest deformations were observed for resin alone, ICFRC+R and GFRC+R. The results were slightly different in the incisal region probably due to the greater amount of veneering material in this area. Conclusions: When used to realize full-arch frameworks, Au and Ti allow a predictable mechanical behavior with gradual deformations with increasing load. UCFRC also demonstrated good outcomes and less deflection than ICFRCs when loaded. The GFRC full-arch framework may be a valid alternative, however showed greater deflections. Further studies are needed in order to evaluated how different prosthesis design and material thickness might affect the outcomes.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

Pharmacists must acquire the necessary knowledge to provide better drug therapy to patients. In other words, educational programs need to facilitate behavioral changes among pharmacists. Therefore, this study aimed to evaluate how the behavior of pharmacists changed after attending a palliative care educational program. We conducted a web-based questionnaire survey examining the behavior of pharmacists regarding palliative care before participating in the program, two months after participating in the program, and eight months after participating in the program, to determine the behavior and changes over time. For all questions, scores were higher at two and eight months after attending the program than before attending the program (P &lt;0.05). In addition, no significant difference was observed between two and eight months after attending the program for all questions (P =0.504-1.000). The knowledge gained from the educational program was used to repeatedly intervene with patients with cancer, to address the various symptoms they experienced and maintain their behavior. The proven effectiveness of this program serves as a stepping stone for a nationwide rollout across Japan’s 47 prefectures.

Aim: To analysis the relationship between healthy adults right ventricular diameter (RVD) and geographical factors. Location: China’s 22 provinces, municipalities and autonomous regions. Methods: Using correlation analysis the relationship between RVD and nine geographic factors, build predictive models by factor analysis. Results: There is significant correlation between RVD and geographical factors, and the annual average temperature is most relevant geographical factors, a predictive model was built by factor analysis: Ŷ = 19.46 + 0.0007072X1 + 0.001034X2 -0.05412X3 -0.001405X4 -0.0006351X5 + 0.02903X6 + 0.01243X7 -0.01033X8 + 0.03816X9 ± 0.63. Then using Kriging interpolation interpolate the geographical distribution of Chinese healthy adult right ventricular diameter reference value in ArcGIS software. Main Conclusion: If geographic factors can be derived in anywhere of China, RVD can be calculated by the model, you can also get RVD from geographical distribution.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

This article is devoted to the results of in-depth analysis of the system of binary-oppositional structures in DNA n-plet alphabets and their algebraic-matrix representations. These results show that the molecular complementary replication of DNA strands is accompanied by the presence of an algebraic version of the principle "like begets like" in matrix representations of DNA alphabets having internal structures. This algebraic version is based on binary-oppositional structures in the genetic molecular system, which can be represented by binary numbers and corresponding matrices of DNA alphabets. The received results allow thinking that the phenomenon "like begets like" (or a complementary replication in a wide sense) is systemic in the genetic organization and is connected with algebraic features of biological organization. Correspondingly, the biological principle "like begets like" can be additionally modeled by algebraic-matrix methods and approaches. Such algebra-matrix modeling of the genetic coding system gives new ways for studying and understanding the key role of the named principle in genetic and other inherited physiological complexes. On this way, the author discovered general rules of stochastic organization of information binary sequences of genomic DNAs of eukaryotes and prokaryotes. The presented rules are connected with information dichotomies of probabilities and corresponding fractal-like trees of probabilities, which fundamentally differ from constructional dichotomies in biological bodies. The received phenomenological data and rules lead to new biological ideas.

In this study, a new type of temperature sensor device was developed. The circular electrode of the thermal sensitive sensor was modified with TMT and O₂ plasma to enhance the conductivity by forming a thin SnOxCy layer on the electrode surface. The Nano-Au particles were subjected to O₂ plasma pretreatment to form peroxide groups on the surface. The thermally sensitive sensor was made by mixing the above-treated Nano-Au particles with N-isopropylacrylamide (NIPAAm) to form solution and then UV-induced grafting polymerization of the NIPAAm-containing solution onto the electrode substrate. The composite hydrogels on the electrode introduce thermo-sensitive polymeric surface films for temperature sensing. Using ambient environment resistance test to measure the resistance, the LCST (lower critical solution temperature) of Nano-Au (MUA) mixed with NIPAAm hydrogel was found to be 32 °C. At ambient temperatures higher than LCST, the electrode resistance decreases linearly.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

Surgical navigation has evolved as a vital tool in maxillofacial surgery, offering precise and patient-specific data. This study explores the clinical applications and accuracy of intraoperative tool tracking in maxillofacial surgery. The research includes 37 patients with various pathologies who underwent surgery assisted by a surgical navigation system using tracked instruments. The study showcases two representative cases: one involving coronoid hyperplasia with mouth opening deficit and another addressing nose-orbital-ethmoidal-frontal ossifying fibroma resection. The results indicate that surgical navigation with tracked instruments provides high precision (<1.5 mm error), reduced surgical time, and less invasive approaches. The study highlights the potential for reproducible outcomes and increased safety, especially in complex cases. Despite some limitations, the synergy between surgical navigation and tracked instruments offers a promising approach in maxillofacial surgery, expanding its applications beyond current practices.

The SBA-15 loaded with methylene blue was successfully prepared by sample adsorption of methylene blue in SBA-15 and is characterized by an XRD, SEM, FTIR, and BET. The photocatalytic activity for methyl orange (MO) degradation was investigated under visible light irradiation under LEDs. Experimental results demonstrate that the SBA-15-MB exhibited higher photocatalytic activity than SBA-15 under visible light irradiation. The degradation efficiency of MO (50 ppm) by SBA-15-MB could reach 80% within 180 min under 25W LED visible light. The photocatalytic activity of SBA-15 could be attributed to the excitation of methylene blue by visible light, the transfer of electrons from methylene blue to SBA-15, and the production of radicals at the surface of SBA-15.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

This study examined the patterns of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) deposition in the small intestine and colon to evaluate the association between histopathological severity of EFEMP1 deposition and constipation and determine if amyloid transthyretin (ATTR) and EFEMP1 deposits can colocalize. In 40 older cases (≥80 years of age), EFEMP1 deposition in the small intestine initiated in the submucosal and subserous vessels, subserous interstitium, and serosa (early stage); progressing to the muscularis propria and peri-Auerbach plexus area (intermediate stage); and finally, spreading diffusely to areas, excluding the mucosa and muscularis mucosa (advanced stage). The colon had a similar pattern of progression. During the middle-to-advanced stages, amyloid formation was observed in some vascular and serous deposits. We identified a subgroup of cases in which EFEMP1 deposition was the only presumed cause of constipation. Additionally, we demonstrated the colocalization of ATTR and EFEMP1 deposition. Apple-green birefringence was detected under polarized light only in approximately one-half of the cases in the small intestine and one-third of the cases in the colon. These findings emphasize that EFEMP1 deposits may be associated with lower gastrointestinal pathological conditions. Given the challenges of histopathological diagnosis on Congo red-stained specimens, we recommend the combined use of elastic fiber staining and immunohistochemistry for EFEMP1 to prevent overlooking this deposition.

Abstract: Kiwifruit, a perennial horticultural crop known for its nutritional value, faces significant challenges due to biotic and abiotic stresses, affecting its yield and quality. Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we investigated the expression patterns of kiwifruit LRR-RLPs under various stress conditions, including pathogen stress, heat stress, waterlogging stress, and copper stress. Through genome and transcriptome analyses, we identified a total of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5' kiwifruit, respectively, classified into 9 subgroups based on phylogenetic relationships. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Using RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP genes in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

Agricultural drainage canals that connect upstream fish spawning areas to downstream rivers and lakes serve as crucial habitats for migrating fish. However, disconnections, such as drops and chutes, have been constructed in these canals due to agricultural modernization and flood control measures, hindering the movement of fish with limited swimming abilities. Portable fishways offer a promising solution to reconnect water bodies in agricultural canals, as they can be easily removed during high water discharges to avoid impeding the canals' drainage function. In addition to experimental assessments of fishway functionality, employing a hydrodynamic model to explore effective placement strategies for portable fishways is essential to maximize their effectiveness. This study presents a method to determine the best horizontal location of a portable fishway in an agricultural drainage canal using two-dimensional hydrodynamic simulations within the specified cases. The applicability of this method is demonstrated by addressing the positioning challenge of a portable fishway on a chute in an agricultural drainage canal in Japan. Results indicate that the proposed method allows for the selection of a suitable location, considering preferable hydraulic conditions both within the portable fishway and around its entrance.

The asymptotic dynamics of the classes of rational difference equations (RDEs) of third order defined over the positive real-line as $$\displaystyle{x_{n+1}=\frac{x_{n}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-1}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-2}}{ax_n+bx_{n-1}+cx_{n-2}}}$$ and $$\displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-1}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-2}}}$$ is investigated computationally with theoretical discussions and examples. It is noted that all the parameters $a, b, c$ and the initial values $x_{-2}, x_{-1}$ and $x_0$ are all positive real numbers such that the denominator is always positive. Several periodic solutions with high periods of the RDEs as well as their inter-intra dynamical behaviours are studied.

To date, viruses closely related to SARS-CoV-2 have been reported in four bat species: Rhinolophus acuminatus, Rhinolophus affinis, Rhinolophus malayanus, and Rhinolophus shameli. Here, we analysed 343 sequences of the mitochondrial cytochrome c oxidase subunit 1 gene (CO1) from georeferenced bats of the four Rhinolophus species identified as reservoirs of SARS-CoV-2-like viruses. Haplotype networks were constructed in order to investigate patterns of genetic diversity among bat populations of Southeast Asia. No strong geographic structure was found for the four Rhinolophus species, suggesting high dispersal capacity. The ecological niche of SARS-CoV-2 like viruses was predicted using the four localities of bat SARS-CoV-2-like viruses and the localities where bats showed identical or very similar CO1 haplotypes than virus-positive bats. The ecological niche of SARS-CoV-like viruses was deduced from the localities where bat SARS-CoV-like viruses were previously detected. The results show that the ecological niche of SARS-CoV2-like viruses includes several regions of mainland Southeast Asia whereas that of SARS-CoV-like viruses is mainly restricted to China. In agreement with these results, human populations in Laos, Vietnam, Cambodia, and Thailand appear to be much less affected by the Covid-19 pandemic than other countries of Southeast Asia. In the climatic transitional zone between the two ecological niches (southern Yunnan, northern Laos, northern Vietnam, and possibly Hainan and Taiwan), genomic recombination between highly divergent viruses is more likely to occur. Since recombinant viruses can threaten the benefit of vaccination campaigns, these regions should be under surveillance.

(S)-1-Methyl-2-oxoimidazolidine-4-carboxylic acid 1 is an analog of (S)-pyroglutamic acid, a key component of naturally occurring peptide hormones and synthetic pharmaceutical candidates. Reaction of (S)-2-amino-3-(methylamino)propionic acid with COCl2 and aqueous NaHCO3 followed by ion exchange afforded 1, which was recrystallized from acetonitrile and then characterized by IR, 1H NMR, 13C NMR, polarimetry, elemental microanalysis, high resolution mass spectrometry and single crystal X-ray diffraction. The acid 1 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.2275(4) Å, b = 8.3963(5) Å, c = 24.9490(14) Å. The X-ray crystal structure reveals that two distinct conformers of 1 occur at alternating positions within helices which are supported by hydrogen-bonding. Each molecule of 1 is linked to its two neighbors in the helix by a total of three hydrogen bonds and four molecules of 1 are contained within each turn of the helix. The pattern of hydrogen bonds illustrates a preference for the carboxylic acid group to act as a hydrogen bond donor and for the urea unit to be a hydrogen bond acceptor.

We propose a method for creating parallel Bessel-like vortical optical needles with an arbitrary axial intensity distribution via superposition of different cone-angle Bessel vortices. We analyze the interplay between the separation of individual optical vortical needles and their respective lengths and introduce a super-Gaussian function as their axial profile. We also analyze the physical limitations to observe well-separated optic needles, as they are influenced by mutual interference of the individual beams. To verify our theoretical and numerical results, we generate controllable spatial arrays of individual Bessel beams with various numbers and spatial separations by altering the spectrum of the incoming laser beam via the spatial light modulator. We demonstrate experimentally how to implement such beams using a diffractive mask. The presented method facilitates the creation of diverse spatial intensity distributions in three dimensions, potentially finding applications in specific microfabrication tasks or other contexts. These beams may have benefits in laser material processing applications such as nanochannel machining, glass via production, modification of glass refractive indices, and glass dicing.

Infertility is affecting around 20 % of couples in the age of procreation but however in some societies as many as one-third of all couples are unable to conceive. Different factors are contributing to male fertility declining such us endocrine disruptors environmental and professional exposures, oxidative stress and life style changes with risks of de novo epigenetics dysregulation. Since the fantastic development of new technologies of Omes and Omics , the contribution of inherited or de novo genomes and epigenome disorders contributions in male infertility are more elucidated and relevant. More than somatic genome investigation of infertile men (from chromosome to single or multiple gene point mutations) many others techniques become available in molecular andrology laboratory to investigate the genome and epigenome integrity, the maturation and the competency of the spermatozoa and its physiological environment. All those new methods of assessment are demonstrating the role of genetics and epigenetics disorders contribution on reproductive pathology and are helping the professional of assisted reproductive technology to propose different management strategy of male infertility to improve the clinical outcomes and minimize the risk of genetics or metabolic disorders at birth.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p&lt;0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

Intergenerational Justice entitles the maximum retention of Earth’s Biodiversity. The United Nations COP 15 committed to the protection of 30% of Earth’s terrestrial environments to provide Biospheric Sustainability. However, proactive amphibian sustainability needs support from amphibian Reproduction Technologies, Biobanking, and Conservation Breeding Programs [RBCs]. These technologies include the reliable practice of stimulation of reproduction and the collection of sperm and oocytes, refrigerated and cryopreserved sperm storage, in vitro fertilization. Emerging technologies promise the perpetuation of species solely from biobanked biomaterials. However, although exemplary national programs for amphibian RBCs are now established in the USA and Australia, these potentials are not fully realised resulting in unacceptable biodiversity loss. To fully realise these potentials an independent and democratic global organisation is proposed to, 1) focus on the bioregions with the highest amphibian biodiversity, 2) maximise regional inclusion in international initiatives, and 3) provide for maximum community engagement and financial resources. We present the first overall multidisciplinary review of amphibian RBCs, including their geopolitical, cultural, and scientific background, along with their development and application to economically, efficiently, and reliably, perpetuate amphibian biodiversity. We provide genetic models, the potential for diploid cell cryopreservation to perpetuate species, along with significant new information on methodologies and techniques, and standardise nomenclature for specificity in publications and media consistency.

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let’s delve into the mathematical intricacies of these sequences. We’ve previously devised a mathematical approach for defining a “healthy” sequence (10.14218/GE.2023.00079). This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt−1, it must be aperiodic, fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let’s explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI equation (10.3390/dynamics4010001). In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a “wild” dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find applications in cancer research.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

The measurement of discrimination in employment is a key variable in understanding dynamics in the nature of and change in ‘race relations’. Measuring such discrimination using ‘situation’ and ‘correspondence’ tests was influenced by John Rex’s sociological analyses, begun in in England in the 1960s, and replicated in Europe and America in later decades. This literature is reviewed, and the methodologies of testing for employment discrimination are discussed. Recent work in Britain and The Netherlands is considered in detail in the light of changing social structures, and the rise of Islamophobia. Manchester, apparently the city manifesting the most discrimination in Britain, is considered for a special case study, with a focus on one individual, a Muslim woman seeking intermediate level accountancy employment. Her vita was matched with that of a manifestly indigenous, white Briton. Submitted vitas (to 1,043 potential employers) indicated significant discrimination against the Muslim woman candidate. Results are discussed within the context of Manchester’s micro-sociology, and Muslim women’s employment progress in broader contexts, drawing on our work in Jordan and Palestine. We conclude with the critical realist comment that the “hidden racism” of employment discrimination shows that capitalist societies continue to be institutionally racist, and the failure to reward legitimate aspirations of minorities pushes ethnic minorities into a permanent precariat, with implications for social justice and social control, which denies minority efforts to “integrate” in society’s employment systems.

Separase is a key cysteine protease to separate sister chromatids through digestion of cohesion ring that inhibits chromosome segregation as trigger of metaphase–anaphase transition in eukaryotes and highly regulated its activity by binding with securin and cyclinB-CDK1 complex. Those bindings prevent proteolytic activity of separase until the onset of anaphase. Chromosome missegregation and aneuploidy are frequently observed in malignancies. However, there are some difficulties for biochemical examinations due to instability of separase in vitro and a few spatiotemporal resolution approaches monitoring live separase activity throughout mitotic processes. Here we have developed FRET-based molecular sensors including GFP variants with separase cleavable sequences as donor and covalently attached fluorescent dye as acceptor molecules applicable to conventional live cell imaging and flow cytometric analysis because of efficient live cell uptake. We investigated performance of equivalent molecular sensors localized or not localized inside nucleus under cell cycle control using flow cytometry. Synchronized cell cycle progression rendered significant separase activity detections in both molecular sensors. We obtained consistent outcomes with localized molecular sensor introduction and cell cycle control by fluorescent microscopic observations. We thus established live cell separase activity monitoring systems specifically or statistically that could lead to elucidate separase properties in detail.

The swelling behavior of titanium-modified austenitic stainless steel 15-15Ti was investigated by pre-implantation of He at room temperature followed by Ni irradiation at 580 °C to peak doses of 120, 240 and 400 dpa. Relatively smaller cavities were observed in the zone of helium implantation while large cavities appeared in the region near the damage peak. A correction formula of the dpa curve was proposed and applied for samples with large swelling. It is found that the steady-state swelling rate of 15-15Ti keeps at ~1% /dpa even to high doses. By comparing the swelling data of the helium-implanted and helium-free regions at same doses, 70 dpa and 122 dpa, the suppression of excessive helium on swelling can be deduced at such doses.

Background: The purpose of this study was to ascertain the reliability of two 15-sec sprint cycling tests in men and women to estimate the maximum rate of glycolysis or lactate production (VLa-Max). Methods: Eighteen men and twelve women completed two sprint sessions over 1-week. A 10-min warm-up preceded a 3 µl blood lactate (BLC) sample, after which a 15-sec sprint was completed; cyclists then rested passively while multiple lactate samples were taken until levels peaked. VLaMax was calculated as (Peak BLC – Pre BLC) * (15-sec – Talac)-1. Trial differences and reliability across trials were analyzed using a paired-sample t-test, Pearson correlation, ICC, and Bland-Altman analysis with α=0.05 for all tests; data are reported as mean ± sd. Results: Power (W) was similar across trails (773.0 ±143.5 vs. 758.2 ± 127.4; p = 0.333) and coefficient of varia-tion (CV) of 4.7%. VLaMax was similar (0.673 ± 0.024 vs 0.635 ± 0.237; p = 0.280), but only moder-ately reliably across trials with a CV, ICC, and R value of 18.6%, 0.661, and 0.67, respectively. Conclusions: A 15-sec VLaMax cycling sprint is moderately reliable being affected both by the lac-tate measurement and other variables used in the calculation. More research may offer ways to improve reliability.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responds to immunotherapy. The relationships between tumor DNA damage response, the immune system and immunotherapy have recently attracted attention. Accumulating evidence indicate that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsible to immunotherapy, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of gastric adenocarcinoma. The results showed that DRGS high score patients showed significantly better therapeutic outcomes compared to DRGS low score patients (P < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocytes infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival and may benefit more from ICB therapy, as compared to the low-score patients. Therefore, the DRGS and its scoring system may have implications in tailoring immunotherapy in gastric cancers.

The enormous increase in the volume of Earth Observations (EOs) has provided the scientific community with unprecedented temporal, spatial, and spectral information. However, this increase in the volume of EOs has not yet resulted in proportional progress with our ability to forecast agricultural systems.This study examines the applicability of EOs obtained from Sentinel2 and Landsat8 for constraining the APSIM-Maize model parameters. We leveraged leaf area index (LAI) retrieved from Sentinel2 and Landsat8 NDVI to constrain a series of APSIM-Maize model parameters in three different Bayesian multi-criteria optimization frameworks across 13 different sites across the U.S Midwest. A time variant sensitivity analysis was performed to identify the most influential parameters driving the LAI estimates in APSIM-Maize model. Then surrogate models were develop using random samples taken from the parameter space using Latin hypercube sampling to emulate APSIM’s behavior in simulating NDVI and LAI at all sites. Site-level, global and hierarchical Bayesian optimization models were then developed using the site-level emulators to simultaneously constrain all parameters and estimate the site to site variability in crop parameters. For within sample predictions, site-level optimization showed the largest predictive uncertainty around LAI and crop yield, whereas the global optimization showed the most constraint predictions for these variables. Lowest RMSE for within sample yield prediction was found for hierarchical optimization scheme (1423 Kg ha−1) while the largest RMSE was found for site-level (1494 Kg ha−1). In out-of-sample predictions within the spatio-temporal extent of the training sites, global optimization showed lower RMSE (1627 Kg ha−1) compared to the hierarchical approach (1822 Kg ha−1) across 90 independent sites in the U.S Midwest. On comparison between these two optimization schemes across another 242 independent sites outside the spatio-temporal extent of the training sites, global optimization also showed substantially lower RMSE (1554 Kg ha−1) as compared to the hierarchical approach (2532 Kg ha−1). Overall, EOs demonstrated their real use case for constraining process-based crop models and showed comparable results to model calibration exercises using only field measurements.

The features of a class of cubic curves with a shape factor are analyzed by means of the theory of envelope and topological mapping. The effects of the shape factor on the cubic curves are made clear. Necessary and sufficient conditions are derived for the curve to have one or two inflection points, a loop or a cusp, or to be locally or globally convex. Those conditions are completely characterized by the relative position of the edge vectors of the control polygon and the shape factor. The results are summarized in a shape diagram, which is useful when the cubic parametric curves are used for geometric modeling. Furthermore we discussed the influences of the shape factor on the shape diagram and the ability for adjusting the shape of the curve.

Previous research has proven that one of the fundamental requirements for ensuring increased profitability and economic competitiveness of offshore-based projects is co-locating different technologies within the same marine space. This paper presents a number of techno-feasibility analyses for floating offshore technologies for the Maltese Islands, located in the Central Mediterranean Sea. The first part compares the feasibility of offshore-based solar photovoltaic prices with those onshore, taking into consideration Malta’s land prices. The second part considers the use of a novel floating breakwater design that integrates energy storage. The breakwater is used to create a sheltered water area in deep waters for a multi-use marine park. Different revenue streams for the floating break water are considered, including renting the sheltered marine space out to operators of floating solar farms, aquaculture cages and vessel berthing facilities, and the provision of energy storage services. It is found that the combined income from the multiple revenue streams is still insufficient to justify the investment and that financially support from Government is essential to render the floating breakwaters viable.

In this paper, we consider the formation of quantum black holes (QBHs) through a genuine quantum process. We treat particles at the Planck energy as QBHs. The Hawking temperature and entropy of QBHs are estimated. We also show that a QBH has a discrete energy spectrum. By analogy with supersymmetric theory, the mass of the superpartner of a QBH is estimated.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

Suicide is a major public health concern in South Korea, and self-poisoning by pesticides is one of the common methods of suicide. Pesticide ban policies have been successful for suicide prevention; however, no studies have shown their effect according to occupational groups. The present study analyzed suicide and suicide by pesticide rates among South Korean workers age 15-64 in 2003-2017, their associations with occupational groups, and the impact of three major economic indices on these factors. Workers in the agriculture, forestry, and fishery industries have relative risks of 5.62 (95% CI: 5.54-5.69) for suicide overall and 25.49 (95% CI: 24.46-26.57) for suicide by pesticide. The real gross domestic product (RGDP) has a positive association with suicide overall only in the last five-year period investigated in this study, and the unemployment rate consistently has a positive association. The economic status and policy for suicide prevention affect suicide and suicide by pesticide rates differently among occupational groups and different time periods. Policy addressing suicidal risk for different occupational groups should be of concern in South Korea.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

There is a need to find methods to intensify the anaerobic digestion process. One possibility is the use of pre-treatment techniques. Many laboratory tests confirm their effectiveness, but in most cases, there is no verification work carried out on industrial plants. The aim of the research carried out under laboratory conditions and on a large scale was to determine the technological and energy efficiency of the use of hydrodynamic cavitation in the pre-treatment of a waste mixture from dairy farms. It has been shown that hydrodynamic cavitation significantly increases the concentration of organic compounds in the dissolved phase. In the most effective variants, the increase in the content of these indicators was over 90% for both COD and TOC. The degree of solubilisation achieved was 49±2.6% for COD and almost 52±4.4% for TOC. Under laboratory conditions, the highest effects of anaerobic digestion were achieved after 10 minutes of pre-treatment. The amount of biogas was on average 367±18 mL/gCOD and the amount of methane 233±13 mL/gCOD. Further large-scale optimisation trials showed that after 8 minutes of hydrodynamic cavitation, the biogas yield was 327±8 L/kgCOD with a CH4 content of 62.9±1.9%. With this variant, the net energy yield was 66.4±2.6 kWh/day, a value that was 13.9% higher than the original variant with 10 minutes of disintegration and 3.1% higher than the variant without pre-treatment.

This review article discusses the involvement of the Brain-Derived Neurotrophic Factor (BDNF) in the control of pain. BDNF, a neurotrophin known for its essential role in neuronal survival and plasticity, has garnered significant attention for its potential implications as a modulator of nociception and pain. This comprehensive review aims to provide insights into the multifaceted interactions between BDNF and pain pathways, encompassing both physiological and pathological pain conditions. I delve into the molecular mechanisms underlying BDNF's involvement in pain processing and discuss potential therapeutic applications of BDNF and its mimetics in managing pain. Furthermore, I highlight recent advancements and challenges in translating BDNF-related research into clinical practice.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

La integration (at various nominal contents) in SBA-15 prepared under acidic medium was intended from corresponding direct nitrate addition during mesoporous silica formation. Materials were impregnated with Pt (1.5 w%) and studied through several textural (N2 physisorption), structural (XRD, TG-DTG) and surface (FTIR, STEM-HAADF, SEM-EDS, NH3 and CO2 TPD) instrumental techniques. Pt-impregnated solids were tested in phenol hydrodeoxygenation (HDO, T=250 °C, 3.2 MPa, batch reactor, n-decane as solvent). Catalytic activity (in pseudo first order kinetic constant, kHDO basis) was related to Pt dispersion which was, however, not determined by nominal rare earth content. Determining actual composition of modified SBA-15 materials is crucial in reaching sound conclusions regarding their physicochemical properties, especially when La modifier is directly added during mesoporous matrices formation where efficient interaction among constituents could be difficult to get. Otherwise, results from some characterization techniques (N2 physisorption and FTIR, for instance) could be misleading and even contradictory. Indeed, extant modifier precursors when under SBA-15 synthesis conditions could affect the properties of prepared materials even though they were absent in obtained| formulations. Performing a simple compositional analysis could eliminate uncertainties regarding the role of various modifiers on characteristics of final catalysts. However, several groups have failed in doing so.

Urban accessibility represents one of the great challenges of the contemporary city, which is required to adopt sustainable development models in line with the UN Agenda 2030 objectives, recently confirmed by the health emergency. Urban accessibility and walkability are topics closely related to those aiming at a livable, healthy and inclusive city, based on a system of high-quality public spaces and on a network of services and infrastructures. However, these principles collide with the fragmentation of many urban contexts, built following vehicular accessibility needs. Within this framework, the city of Cagliari represents an interesting case study as it is affected by the disposal of public properties which appear as “enclaves” in the historic urban fabric. This research aims to evaluate if and in which terms the abandoned assets can facilitate the development of the 15-minutes city, as a city reducing the need to move over a certain time and space and therefore granting a more equal access to urban services to a wide range of citizens. This is done by proposing indexes defined as porosity, crossing and attractiveness, which constitute a combined index to improve the pedestrian accessibility in the “central places” of the contemporary city, where the walkability can also become a possible “free choice” for a new healthy lifestyle. These indexes were calculated for the most significant large disused public buildings in the historic center to guide future scenarios towards a 15 minutes city.

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

： Anti-MDA5 antibody bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) &amp;/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD especially with regards to the mortality rate are unknown. We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Thirty-nine (55%) patients presented with DM/PM but 32 (45%) didn’t. Twenty-two of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among 32 patients who didn’t have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio [OR]=1.816, P=0.032), presence of anti-Ro-52 antibody (OR=1.676, P=0.018), elevated C-reactive protein (CRP, OR= 4.354, P&lt;0.001) and carcinoembryonic antigen (CEA, OR=2.625, P=0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p=0.009), CRP (p=0.001), CEA (p=0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR=0.245, P=0.017) and multivariate (OR= 0.058, P=0.036) regressions, indicating that they may be a protective factor from RPILD (OR= 0.543, P=0.008) or fatality (OR= 0.707, P=0.012), which was also demonstrated in subgroup analyses. In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might be conversely a protective factor in anti-MDA5+ patients.

This study involved the fabrication of a set of Aluminum ion-grafted SBA-15 utilizing ethylene-diamine and trimethylamine ionic liquids. The primary objective was to examine the impact of the fabrication environment on the physicochemical characteristics of the catalysts. Comprehensive characterization of the Al-SBA-15 catalysts was conducted using various techniques, including XRD, FTIR, surface area, pyridine FTIR, 27Al-NMR, TGA, HRTEM, and FESEM, to analyze their physicochemical characteristics. Furthermore, the acidic characteristics were examined by con-ducting potentiometric titration in a nonaqueous solvent and employing FTIR spectroscopy to an-alyze the chemisorbed pyridine. The effectiveness of the fabricated acid materials was evaluated by testing their performance in the acetic acid esterification with butanol. The findings obtained reveal that the mesostructured of SBA-15 remains intact following the successful inclusion of Al3+ ions into the silica frameworks. Additionally, a remarkable enhancement in the existence of both Bronsted and Lewis acid centers is noted due to the grafting process of Al3+ ions. At temperatures of 80°C and 100°C, the reaction in Al-SBA-15(T-120) proceeds swiftly, reaching approximately 32% and 38% conversion, respectively, within a span of 110 minutes. The excellent catalytic performance observed in the esterification reaction can be attributed to two factors: the homogeneous distribution of Al3+ ions within the SBA-15 frameworks and the acidic character of Al-SBA-15. The findings further indicate that the grafting process for incorporating Al3+ ions into the silica matrix is more efficient.

Raman Spectroscopy has long been anticipated to augment clinical decision making, such as classifying oncological samples. Unfortunately, the complexity of Raman data has thus far inhibited its routine use in clinical settings. Traditional machine learning models have been used to help exploit this information, but recent advances in deep learning have the potential to improve the field. However, there are a number of potential pitfalls with both traditional and deep learning models. We conduct a literature review to ascertain the recent machine learning methods used to classify cancers using Raman spectral data. We find that while deep learning models are popular, and ostensibly outperform traditional learning models, there are many methodological considerations which may be leading to an over-estimation of performance: primarily, small sample sizes which compound upon sub-optimal choices regarding sampling and validation strategies. Amongst several recommendations is a call to collate large benchmark Raman datasets, similar to those that have helped transform digital pathology, which researchers can use to develop and refine deep learning models.

Spondyloptosis is a condition where there is complete dislocation of L5 over sacrum. It is a form of spinal dislocation in which one spinal segment is lodged in the anterior or posterior space of another or advanced spondylolisthesis [1]. Treatment is usually spinal fusion depending on the level of lesion [2]. This clinical case is of a 15 year old male with a history of fall from auto-rickshaw followed by a blunt trauma from a heavy iron rod falling over his abdomen. There was no history of loss of consciousness, but the patient had an excruciating pain over back immediately after the incident. Patient is now paraplegic with loss of sensation below L5 along with loss bladder and bowel control since the time of injury. The T1 weighted MRI of spine revealed grade 5 anterior lysthesis of L5 over S1 level with complete spinal cord transaction. The patient was operated to restore the vertebral alignment with pedicle screws and rods. After 3 months, patient is now treated for neuro-musculoskeletal , genitourinary and genitointestinal function with biofeedback, pelvic floor exercises and timed voiding [3]. When a patient has issues with urine retention, Valsalva manoeuvres, Crede's method, suprapubic tapping, and anal stretching are employed to help them void more effortlessly [4].

Background: Significant national and global costs were incurred from recent emerging infectious disease outbreaks, notably H1N1 highly pathogenic influenza, Zika and Severe Acute Respiratory Disease (SARS), both in the medical sphere and within the socioeconomic context around it. With forecasts expecting an increase in direct and indirect burden of novel infectious disease events, costs of future outbreak events are likely to be exacerbated. In this scope, it is critical for countries to identify this trend and work towards minimizing costs while continuing to improve prevention, treatment and mitigation. Objectives: The impacts of the West Africa Ebola crisis have largely focused on the response to the outbreak abroad. The aim of this paper was to determine the direct and indirect domestic costs of the Ebola Virus Disease (EVD) introduction into the United States (U.S.), compare the economic consequences of the epidemic with other disease outbreaks and identify the primary drivers of such costs to leverage more global health preparation to prevent, prepare for, and respond to disease threats more effectively. Methods: I conducted a literature review of 1) EVD cases documented by the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), 2) scientific articles identifying the costs of Ebola for the U.S. and countries around the world and 3) grey literature on treatments and public reactions. Extrapolating data from these sources, I then performed a cost-analysis of direct costs (preparation, treatment and contact tracing) and indirect costs (loss of productivity owing to disease, death, and risk avoidance behaviors) of the disease. Findings: The country spent between $300-$700 million in direct costs. Additionally, roughly $200-$340 million were forgone as results of loss of productivity from to disease, death or social risk avoidance behaviors. The cost-per-case for the United States was vastly higher than for any other country. Conclusions: High direct costs suggest that either the United States took disproportionate preparative measures to mitigate a potential American outbreak or were unprepared for a potential outbreak of this magnitude. The significant risk avoidance behavior estimates hint that forces having the ability to shape social attitudes and norms – namely traditional and online media – played a significant role in driving social behavior towards fear of exposure to others. The findings reinforce that outbreaks occurring in a single part of the world can have dramatic economic effects globally, even in areas with existing public health capacity and other preventive measures, highlighting the need for change in global health systems to shift from a passive responder and incorporate other societal actors to effectively reduce the ever-increasing costs of disease threats.

The most widely distributed bla_CTX-M gene on a global scale is bla_CTX-M-15. The dissemination has been associated with clonal spread and different types of mobile genetic elements. This study aimed to review and describe the genetic environments of bla_CTX-M-15 gene detected from Enterobacteriaceae in published literature from Africa. A literature search for relevant articles was done through PubMed, and Google Scholars electronic databases, 43 articles from 17 African countries were included in the review based on the eligibility criteria. Insertion sequences were reported as part of the genetic environment of bla_CTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including ISEcp1, IS26, orf447, IS903, and IS3 have been detected associated with the genetic environment of bla_CTX-M-15 in Africa. Seven different genetic patterns were seen in bla_CTX-M-15 genetic environment. Insertion sequence ISEcp1 was commonly located upstream of the end of the bla_CTX-M-15 gene while insertion sequence orf477 was located downstream. In some studies, ISEcp1 was truncated upstream of bla_CTX-M-15 by insertion sequences IS26 and IS3. Class 1 integron (Intl1) was most reported to be associated with bla_CTX-M-15 (13 studies), with Intl1/dfrA17–aadA5 being the most common gene cassette array. IncFIA-FIB-FII multi-replicons and IncHI2 replicon types were the most common plasmid replicon types that horizontally transfer bla_CTX-M-15 gene. Aminoglycoside modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with bla_CTX-M-15 gene on plasmids. This review revealed the predominant role of ISEcp1, Intl1and IncF plasmid in the mobilization and continental dissemination of the bla_CTX-M-15 gene in Africa.

Pigs are used as laboratory animals in preclinical studies on medical devices for cardiac surgery. On the one hand, the anatomy of the cardiovascular system of these animals has been well studied and acknowledged suitable for use and testing of new cardiovascular devices developed for humans. On the other hand, there are no morphometric characteristics of the aortic root and other parts of it in pigs with different weights. This can lead to difficulties in the work of researchers and even result in the death of experimental animals due to the discrepancy in the size of the implantable devices. Thus, such information is essential to improve the efficiency of surgical technologies used in the correction of aortic pathologies in its various sections. The purpose of our research is to study the anatomy of the aorta in mini-pigs, and to assess whether the size, age, and sex of animals affect the size of the main structures in their aorta. In addition, we attempted to compare the results obtained by the method of transesophageal echocardiography (TEE) and angiography. We studied 28 laboratory mini-pigs weighing from 40 to 105 kg, and then we compared our results with other studies and did not find any relationship between the external somatometric characteristics of animals and the size of their aorta. Each animal has an individual anatomy, so they are to be examined in terms of preoperative planning by any available method - echocardiography, angiography or multispiral computed tomography (MRI).

In pediatric burn care, achieving swift healing with minimal complications remains paramount. This investigation assesses polyhexamethylene biguanide (PHMB)'s role in managing superficial partial-thickness burns in children, focusing on the effects of various patient-specific factors on recovery. Through a retrospective analysis of 27 pediatric cases treated with PHMB, we explored the impact of age, burn size, dressing frequency, treatment delay, cold therapy application, and analgesic usage on the duration until reepithelialization. Notably, the majority of patients benefited from early cold therapy, yet only 1 in 3 patients received analgesics. The study reveals a mean healing time of 8.78 days, with the extent of the burn showing a strong correlation to recovery speed. Most treatments were managed outpatient, evidenced by a negligible average hospital stay. Impressively, the intervention recorded no complications. Our findings endorse PHMB as a promising treatment for second-degree burns in young patients, offering healing efficiency on par with or surpassing traditional methods, without increasing complication risks. This investigation underscores the necessity for continued exploration into the optimal application of prehospital interventions and the comprehensive benefits of PHMB in pediatric burn management, advocating for future research aimed at assessing long-term outcomes, including scar quality and patient satisfaction.

Time is a component quantity of various measurements and is also used on its own to sequence events, to compare the duration of events or the intervals between them, and to quantify rates of change of quantities in material reality or in the conscious experience [1]. The measuring equipment well might happen to be a clock. By making a presupposition that clock is Time, it is perceived experimentally that “Time exhibits wave-like properties”

. Background: Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. Methods: This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical, functional details (“Glasgow Outcome Scale – Extended”, “Functional Independent Measure”, Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. Results: 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability to be partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working –taking into account limitations due to the traumatic event, versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. Conclusions: Rehabilitation should adequately emphasize “vocational rehabilitation” because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.