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.

Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N²-thiophencarbonyl- and N²-tosyl anthranilamides 1-20 and six amidino N²-thiophencarbonyl- and N²-tosylanthranilamides 21-26 were synthesized and evaluated prothrombin time (PT) and activated partial thromboplastin time (aPTT) using human plasma at concentration 30 μg/mL in vitro. From these results, compounds 5, 9, and 21-23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21-23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21-23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced U46619 in vitro and ex vivo. N-(3'-Amidinophenyl)-2-((thiophen-2''-yl)carbonyl amino)benzamide (21) was most active.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

The research sought to investigate the long term characteristics of wind in the Kisii region (elevation 1710m above sea level, 0.68^oS, 34.79^o E). Wind speeds were analyzed and characterized on short term (per month for a year) and then simulated for long term (ten years) measured hourly series data of daily wind speeds at a height of 10m. The analysis included daily wind data which was grouped into discrete data and then calculated to represent; the mean wind speed, diurnal variations, daily variations as well as the monthly variations. The wind speed frequency distribution at the height 10 m was found to be 2.9ms^-1 with a standard deviation of 1.5. Based on the two month’s data that was extracted from the AcuRite 01024 Wireless Weather Stations with 5-in-1 Weather Sensor experiments set at three sites in the region, averages of wind speeds at hub heights of 10m and 13m were calculated and found to be 1.7m/s, 2.0m/s for Ikobe station, 2.4m/s, 2.8m/s for Kisii University stations, and 1.3m/s, 1.6m/s for Nyamecheo station respectively. Then extrapolation was done to determine average wind speeds at heights (20m, 30m, 50m, and 70m) which were found to be 85.55W/m², 181.75W/m², 470.4W/m² and 879.9W/m² respectively. The wind speed data was used statistically to model a Weibull probability density function and used to determine the power density for Kisii region.

Poly(2,6-dimethyl phenyl oxide) (PPO) is known for its low dissipation factor. To achieve insulating materials with low dissipation factor for high-frequency communication application, a monomer-type benzoxazine (P-APPO) and a main-chain-type benzoxazine (BPA-APPO) were prepared from an amine end-capped oligo (2,6-dimethyl phenylene oxide) (APPO). The APPO was prepared from a nucleophilic substitution of a phenol-end capped oligo (2,6-dimethyl phenylene oxide) (a commercial product, SA 90) with fluoronitrobenzene, and followed by catalytic hydrogenation. After self-curing or curing with a dicyclopentadiene-phenol epoxy (HP 7200), thermosets with high-T_g and low-dissipation factor can be achieved. Furthermore, the resulting epoxy thermosets show better thermal and dielectric properties than those of epoxy thermoset cured from its precursor SA90, demonstrating it is a successful modification in simultaneously enhancing the thermal and dielectric properties.

Aims: Chronic coronary syndrome is associated with several risk factors, such as dyslipidemia and hypertension. AIP has been demonstrated to be a biochemical risk factor for coronary artery disease (CAD). This study aimed to determine whether AIP is an effective parameter for estimating obstructive CAD. Methods and Results: A total of 345 patients (mean age 62,2±10,3; 63% male) who underwent coronary angiography were included in this study. Obstructive CAD is defined as having one or more vessels with a stenosis of≥50%. Depending on the presence of obstructive CAD, all patients were divided into two groups. The AIP was significantly higher in the obstructive coronary artery group (AIP; 0,49±0,26 vs. 0,58±0,27, p=0,002). In univariate analysis, AIP was significantly associated with obstructive coronary artery disease [OD:3,74 (CI95% 1,62-8,64), P=0,020]. The AIP was further adjusted for confounding risk factors in three multivariate analysis models. Therefore, all three models showed a significant association. According to ROC analysis, 0.49 is the cut-off value for AIP, and a value above 0.49 indicates 50% coronary artery stenosis Conclusions: AIP may be used in the assessment of cardiovascular risk in patients with stable angina pectoris, and it may also be used to estimate obstructive CAD.

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-like family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which reveal significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~ 90 potential genes that participate in the regulation of the hypertrophic environment (or CVD's Environment). Also, the GO analysis showed genes containing the motif CACCC were enriched for multiple CVD’s, in combination with STRING analysis these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFA) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFA regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFA. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

Large quantities of real-time particle data are becoming available from low-cost particle monitors. However, it is crucial to determine the quality of these measurements. The largest network of monitors in the United States is maintained by the PurpleAir company, which offers two monitors: PA-I and PA-II. PA-I monitors have a single sensor (PMS1003) and PA-II monitors employ two independent PMS5003 sensors. We determine a new calibration factor for the PA-I monitor and revise a previously published calibration algorithm for PA-II monitors (ALT-CF3). From the PurpleAir API site, we downloaded 83 million hourly average PM2.5 values in the PurpleAir database from Washington, Oregon, and California between January 1, 2017 and September 8, 2021. Daily outdoor PM2.5 means from 194 PA-II monitors were compared to daily means from 47 nearby Federal regulatory sites using gravimetric Federal Reference Methods (FRM). We find a revised calibration factor of 3.4 for the PA-II monitors. For the PA-I monitors, we determined a new calibration factor (also 3.4) by comparing 26 outdoor PA-I sites to 117 nearby outdoor PA-II sites. These results show that PurpleAir PM2.5 measurements can agree well with regulatory monitors when an optimum calibration factor is found.

An important moment in the establishment of forestry seed orchards is the formation of their optimal composition, avoiding inbreeding depression in the outgoing seed material which occurs due to crossbreeding between closely related plus trees, the clones of which comprise the orchards. It is possible to minimize the negative effect of inbreeding by considering the hereditary aspect of the heterogeneous seed orchard material. The purpose of our work is to provide a comparative assessment of the formation and lignification of xylem in annual shoots of the plus trees of Scots pine. We investigated the formation and lignification of xylem in the annual shoots of the plus trees of Scots pine (Pinus sylvestris L.), found in natural forests in the Nizhny Novgorod region of the Russian Federation. Their vegetative progeny were cultivated in the clone archive stationed in the same region. Analyzing the one-type of the 1-year shoots, the time that the shoots were cut from the branches corresponded to the presence of plants in the characteristic phenological phases of seasonal development. A histochemical study of xylem was conducted, using the qualitative reactions of phloroglucinol to lignin. The power of xylem development was estimated by counting, in the radial direction, the cell rows from the core to the cambium in the microscope’s field of view. A significant differentiation of plus trees was revealed in a complex of signs characterizing the level of xylem development and the degree of xylem cell lignification in the tissues of annual shoots. Phenotypic differences in the physiological state of plus trees appeared given a leveled ecological background, indicating their genotypic determinism. This was confirmed by an analysis of variance. The share of the influence of differences between the proper plus trees was between 25.16% ± 8.91% and 53.98% ± 5.48% of the total phenotypic variance of the signs of the seasonal state of xylem. Factor analysis was used to reduce the number of considered indicators of xylem physiological state. The results allowed a cluster analysis to be carried out on the basis of the normalized values of the initial xylem features as well as the principal components derived from them. The association of plus trees was done on the basis of the similarity of the multidimensional estimates of xylem seasonal condition. The objects that were the most remote from the others were identified. This information provides a reasonable approach to the formation of an assortment of Scots pine seed orchards.

Cadmium (Cd) is a major heavy metal pollutant and a significant cause of abiotic stress in the environment. Organisms have developed various pathways to protect themselves against Cd stress. MYB protein is a large transcription factor family in plants. Many members of the family have been found to regulate developmental processes and stress responses. However, the function and mechanism of MYB116 are far from clear. In a recent study, we found that MYB116 of Chinese cabbage enhances Cd tolerance in yeast. BrMYB116 is transiently inducible by Cd treatment in Chinese cabbage. When expressed in yeast cells, it enhances tolerance against Cd stress and reduces Cd accumulation in the cells. Further analysis shows that BrMYB116 protein enhances Cd tolerance in yeast cells by activating one target gene that encodes the facilitator of iron transport 3 (FIT3). ScFIT3 is activated through specific binding with its promoter. More importantly, the expression of ScFIT3, leads to a substantial reduction of Cd accumulation in both yeast and Chinese cabbage. This finding implies that a similar network may exist in other biological systems, which presents a promising avenue for enhancing Cd tolerance in plants and developing Cd-resistant crops.

Focusing geophysics to improve recovery factor of hydrocarbon reservoirs adds value and contributes toward ZERO carbon footprint by increasing the recovery factor by of 30-40 % and thus reducing the cost/carbon emission per produced barrel. Thus, the Enhanced Oil Recovery (EOR) market is expected to grow more than 3.5% annually. This will be even more fueled by the Green-House-Gas (GHG) reduction and subsequent CO2 injection into the reservoirs as they are being produced. Presently, geophysics only ac-counts for a small percentage of this market, thus its growth is inevitable since more deterministic observation lead higher operating efficiency. Imaging the fluids (hydro-carbon, water, and CO2) is a key component to optimized production and injection. We designed a novel electromagnetic (EM) acquisition system that combines mul-ti-physics fluid imaging and acquires surface and borehole data with high fidelity. Borehole calibration is needed to upscale reservoir data and parameters to measurement scale. Multiple electromagnetic methods are used as well as microseismics in one layout for Exploration and Production (E & P) problems. Multi-components in electromagnetics allows resolving oil and water-bearing zones equally well while achieving the best ac-curacy suitable for repeat measurements. Because sedimentary basins are intrinsically anisotropic, considering 3-dimensional anisotropy is essential from measurement and 3D modeling viewpoint. Thus, the results have the better subsurface images. Here, we combine hardware design, methodology, 3D modeling, processing, and interpretations into an integrated technology and demonstrate the success with verifiable case histories.

Parkinson’s disease (PD) is the most common cause of movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. It is increasingly recognized as a complex group of disorders presenting widely heterogenous symptoms and pathology. Except for the rare monogenic forms, the majority of the PD cases result from an interaction between multiple genetic and environmental risk factors. The search for these risk factors and the development of preclinical animal models are in progress hand in hand, providing mechanistic insights into the pathogenesis of PD. This review summarizes the studies that capitalize on modeling sporadic (i.e. non-familial) PD using Drosophila melanogaster and discuss their methodology, new findings and future perspective.

(1) Background: Angiotensin II, a major culprit in cardiovascular disease, activates mediators that are also involved in pathological cardiac remodelling. We aimed at investigating the effects of two of them: aldosterone (Ald) and transforming growth factor-beta-1 (TGF-β1 ), on cardiac remodelling in an in vivo model. (2) Methods: Six-week-old male wild-type (WT) and TGF-β1 -overexpressing transgenic (TGF-β1 -TG) mice were infused with subhypertensive doses of Ald for 2 weeks, and/or treated orally with eplerenone from postnatal day 21. Heart’s ventricles were examined: by morphometry, immunoblotting to assess intracellular signalling pathways, RT qPCR to determine hypertrophy and fibrosis marker genes. (3) Results: TGF-β1 -TG mice spontaneously developed cardiac hypertrophy and interstitial fibrosis, exhibited higher baseline phosphorylation of p44/42 and p38 kinases, fibronectin and ANP mRNA expression. Ald induced a comparable increase in ventricular heart weight-to-body-weight ratio and cardiomyocyte diameter in both strains, but less pronounced increase in interstitial fibrosis in transgenic compared to WT mice (23.6% vs 80.9%, p<0.005). Ald increased phosphorylation of p44/42 and p38 in WT but not TGF-β1 -TG mice. While eplerenone-enriched chow partially prevented Ald-induced cardiac hypertrophy in both genotypes and interstitial fibrosis in WT controls, it completely protected from additional fibrosis in transgenic mice. (4) Conclusions: Ald appears to induce cardiac hypertrophy independently of TGF-β1 , while in case of fibrosis downstream signalling pathways of these two factors probably converge

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

To screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled. Differentially expressed genes (DEGs) were identified. Enrichment analyses performed and the online resources, GOBO and Kaplan-Meier Plotter, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. qRT-PCR and western blot were used to validate the expression of CD274 and IL8 in cell lines and immunohistochemical detected the MIF and VEGFA on tissue microarrays. The results showed that CD274 and IL8 were both upregulated in basal-like cell lines. That MIF expression was dramatically increased in patients with breast cancer metastases (p<0.05) and that VEGFA expression positively correlates with breast cancer pathologic grade (p<0.05).During the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors CD274, IL8, MIF and VEGFA are upregulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here we report that among eighteen representatives of the multifunctional S100 protein family only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatic analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect efficacy of anti-TNF treatment in various diseases.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

In this brief communication, we propose the concept that capillary regression may represent a primary pathogenic process underlying COVID-19 infection, particularly in the serious and life-threatening manifestations of the disease. We suggest that the marked elevations of pro-inflammatory mediators that are observed in these seriously ill patients may directly induce capillary regression and endothelial cell (EC) loss. Recent autopsy studies are demonstrating EC loss leading to widespread microthrombi and associated tissue damage. Recent work has indicated that interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNFα), and thrombin, individually and in combination, can potently cause capillary tube regression in experimental models in vitro and in vivo. Other pro-inflammatory mediators including interferon gamma (IFNγ), interleukin-4 (IL-4), and interleukin-13 (IL-13) were also shown to be pro-regressive and could be relevant mediators in COVID-19 patients. Interestingly, combinations of pharmacologic agents were identified that reduced capillary regression and protected capillary tube networks against these pro-inflammatory mediators. Such an approach might be an important therapeutic option going forward to treat key disease states where capillary regression plays a major underlying pathogenic role. Finally, if capillary regression is occurring in response to these pro-inflammatory mediators during COVID-19 infection, we suggest that combinations of blocking agents directed to these key pro-regressive mediators might be necessary to appropriately treat patients.

In insects, Adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified role of Adipokinetic hormone (AKH) in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-producing cell (APC) transcriptome to identify potential regulatory elements controlling APC activity, and found that a number of receptors show consistent expression levels, including all known dopamine receptors and the Pigment Dispersing Factor receptor (PDFR). We tested the consequences of targeted genetic knockdown and found that AKH expression of RNAi elements corresponding to each dopamine receptor caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation whereas expression of a tethered PDF in APCs resulted in a significantly shorter lifespan. These manipulations caused various changes in locomotor activity under starvation. We used live-cell imaging to evaluate the acute effects of the ligands for these receptors on APC activation. Dopamine application led to a transient increase in intracellular calcium in a sugar-dependent manner. Furthermore, co-application of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones act antagonistically. We also found that PDF application led to an increase in cAMP in APCs, and that this response was dependent on expression of the PDFR in APCs. Together these results suggest a complex circuit in which multiple hormones act on APCs to modulate metabolic state.

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl) propanamides were designed and synthesized, combining benzisothiazole and 4-thiazolidinone in one frame. The aim of the study was to verify their effectiveness to contrast the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, advanced glycation products (AGEs), inflammatory cytokines and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level (IC₅₀ = 40 nM).

Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet-leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we characterized TF-positive extracellular vesicles (EVs) and their cellular origin in 12 patients suffering from severe COVID-19 (time course, 134 samples overall) and 25 healthy controls. EVs exposing phosphatidylserine (PS) were characterized by flow cytometry. Their cellular origin was determined by staining with anti-CD41, anti-CD45, anti-CD235a, and anti-CD105 as platelet, leukocyte, red blood cell, and endothelial markers. We further investigated the association of EVs with TF, platelet factor 4 (PF4), C-reactive protein (CRP) and high mobility group box-1 protein (HMGB-1). COVID-19 patients showed higher levels of PS-exposing EVs compared to controls. The majority of these EVs originated from platelets. A higher amount of EVs in patient samples were associated with CRP, HMGB-1, PF4, and TF, as compared to EVs from healthy donors. In COVID-19 samples, 16.5% of all CD41+ EVs displayed the leukocyte marker CD45, and 55.5% of all EV aggregates (CD41+CD45+) co-expressed TF, which reflects the interaction of platelets and leukocytes in COVID-19 on an EV level.

Shown is the derivation of Lorentz-Einstein k-factor in SRT as an amplitude-term of oscillation-differential equations of second order.This case is shown for classical Lorentz-factor as solution of an equation for undamped oscillation as well as the developed theorem as a second solution for advanced SRT of fourth order with an equation for damped oscillation-states.This advanced term allows a calculation for any velocities by real rest mass.Also accelerated coordinate -frames are discussed.

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.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

The initial development of seahorse juveniles is characterized by low digestion capabilities. Stable isotope analysis is an effective tool in studies of trophic food webs and animal feeding patterns. The present study provides new insights for the understanding of growth and food assimilation in early developing seahorses following a laboratory diet switch. The study was performed in early life stages of the seahorse Hippocampus reidi by assessing the influence of diet shift on changes and turnovers in carbon (δ13C) and nitrogen (δ15N) stable isotope in juveniles. Newborn seahorses were fed for 60 days following two feeding schedules (A6 and A11) based initially on copepods Acartia tonsa and subsequently on Artemia nauplii (since days 6 and 11, respectively). After prey shift, we determined δ13C and δ15N turnover rates as functions of change in either body mass (fitting model G) and days of development (fitting model D), contributions of metabolism and growth to those turnover rates, and diet-tissue discrimination factors. Survival, final dry weight and final standard length for diet A11 were higher compared to diet A6. The shift from copepods to Artemia lead to fast initial enrichments in δ13C and δ15N. Afterwards, the enrichment was gradually reduced until reaching the isotopic equilibrium with diet. In most cases, both fitting models performed similarly. The isotopic analysis revealed that 100% of tissue turnover was attributed to growth in diet A11, whereas 19-25% was endorsed to metabolism in diet A6. Diet-tissue discrimination factors were estimated for the first time in seahorse juveniles, resulting in higher estimates for diet A11 (2.9 ± 0.7‰ for δ13C; 2.5 ± 0.2‰ for δ15N) than in diet A6 (1.8 ± 0.1‰ for δ13C; 1.9 ± 0.1‰ for δ15N). This study highlights the relevance of feeding on copepods and their effect on isotopic patterns and discrimination factors in seahorse juveniles after a dietary shift. Regarding the application of the results achieved to feeding schedules in the rearing of H. reidi, a long period of feeding on copepods during the first days of development is highly recommended.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Hypoxia is one of the most common pathological conditions which results from ischemic injury, trauma, inflammatory conditions, tumors, The adaptation of the body to hypoxia is a phenomenon that is of great importance both in normal conditions and in Most of the cellular response’ reactions to hypoxia is associated with a family of transcription factors called hypoxia-inducible factors (HIF). They induce the expression of a wide range of genes that help cells adapt to a hypoxic HIF functions are currently being extensively studied. In 2019, William G. Kaelin and Gregg Semenza from the USA and Sir Peter J. Ratcliffe from the UK received the Nobel Prize in Physiology or Medicine for the discovery of the basic mechanisms of adaptation to hypoxia and investigation of the role of HIF factor in the regulation of the hormone erythropoietin Based on its pivotal physiological importance, the HIF factor attracts more and more attention as a new potential target for treating a large number of diseases associated with Most of the experimental work dealing with the HIF factor is focused on its role in liver and However, increasing amount of experimental results clearly demonstrates that the HIF factor-based response represents an universal adaptation mechanism for all kinds of tissues, including the nervous system where HIF is critical for regulating neurogenesis, nerve cell differentiation, and neuronal This review provides actual overview about the complex role of HIF-1 in the adaptation of nerve cells to hypoxia with the focus on its potential role by various neuronal

The density functional theory was used to explore the structural, electronic, dynamical, and thermoelectric properties of a VIrSi Half-Heulser (HH) alloy. The minimum lattice constant of 5.69 ( ̊A) was obtained for VIrSi alloy. Besides, the band structure and the projected density of states for this HH alloy were calculated, and the gap between the valence and conduction bands was noted to be 0.2 eV. Also, the quasi-harmonic approximation was used to predict the dynamical stability of the VIrSi HH alloy. At 300 K, the Seebeck Coefficient of 370 and -270 μV.K−1., respectively, was achieved for the p and n-type doping. From the power factor result, the highest peak of 18 X 1011W/cm.K2 is obtained in the n-type doping. The Figure of Merit (ZT) result revealed that VIrSi alloy possesses a high ZT at room temperature, which would make VIrSi alloy applicable for thermoelectric performance.

Peyronie's disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, understanding of the detailed mechanisms and risk factors involved in development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including genetic involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide better understanding regarding involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as provide insight into disease prevention and novel therapeutic interventions.

Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after varies of respiratory viruses infection such as influenza A virus (IFV), respiratory syncytial virus (RSV) and human rhinovirus (hRV). Our analyses reveal that infection of multiple kinds of respiratory viruses or influenza vaccines greatly increased ACE2 expression, suggesting that respiratory viruses infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.

Strong evidence indicates that insulin resistance contributes to the development of Alzheimer´s disease by promoting inflammation, oxidative stress, and blood vessel damage. Conversely, neuroinflammation induces insulin resistance by targeting insulin signaling molecules: the insulin receptor substrates 1 and 2 (IRS1/2). In addition, neuroinflammation is strongly linked to reduced levels of brain-derived neurotrophic factor (BDNF) expression. BDNF is a key factor for neuronal survival, and its expression is compromised in neurodegenerative disorders. In this study, we show that, in a triple-transgenic (3xTg) mice model of Alzheimer’s disease, the BDNF and IRS2 but not the IRS1 mRNA expression levels were reduced in the hippocampus, together with higher levels of TNFα, compared with wild-type mice. Subgroups of control and 3xTg mice received short and long treatments of Abscisic Acid (ABA), a phytohormone with anti-inflammatory and insulin-sensitizing capabilities. We found that the short ABA treatment can increase the IRS1 and IRS2 mRNA expression both in wild-type and 3xTg mice, concomitant with reducing pro-inflammatory cytokine TNFα in 3xTg mice. However, earlier, and thus longer treatments are required to rescue the BDNF mRNA levels. Our data strongly confirm that ABA administration is a potential treatment to prevent Alzheimer´s disease, via lowering neuroinflammation, potentially rescuing insulin signaling molecules and BDNF mRNA expression.

Endothelial integrity plays a major role in homeostasis and is responsive to the numerous endogenous factors released. While its functional role in vascular tone is well described, its role in the pathophysiology of cardiovascular disease is of interest as a potential therapeutic target. We performed a systematic review to provide an overview of new therapeutic and diagnostic targets for the treatment of coronary artery disease related to endothelial dysfunction. Databases of PubMed, Ovid’s version of MEDLINE, and EMBASE were interrogated with appropriate search terms. 28 studies met inclusion criteria and were included in the final systematic review. We identified inflammation, pulmonary hypertension, diabetes mellitus and Fabry disease as pathophysiological mechanisms and explored the therapeutic options related to these conditions including medications such as Canakinumab. Endothelial dysfunction has a key role in several different pathophysiological processes which can be targeted for therapeutic options. Ongoing research should be targeted at making the transition to clinical practice. Further research is also needed on understanding the amelioration of endothelial dysfunction with the use of cardiovascular medications.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

In a changing climate, extreme weather events such as heat waves will be more frequent and could affect grain weight and the quality of crops such as wheat, one of the most significant crops in terms of global food security. In this work, we characterized the response of Triticum turgidum spp. durum wheat to a short-term heat-stress (HS) treatment at transcriptomic and physiological levels during early grain filling in glasshouse experiments. We found a significant reduction in grain weight and size from HS treatment. Grain quality was also affected, showing a decrease in starch content in addition to increments in grain protein levels. Moreover, an RNA-seq analysis of durum wheat grains allowed us to identify 1590 differentially expressed genes related to photosynthesis, response to heat, and carbohydrate metabolic process. A gene regulatory network analysis of HS-responsive genes uncovered novel transcription factors (TFs) controlling the expression of genes involved in abiotic stress response and grain quality, such as a member of the DOF family predicted to regulate glycogen and starch biosynthetic processes in response to HS in grains. In summary, our results provide new insights into the extensive transcriptome reprogramming that occurs during short-term HS in durum wheat grains.

Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a systemic disease rather than a mere disorder of the lungs. Central (respiratory) and peripheral (limb) muscle weakness are among the main pronounced systemic effects of COPD. While the disease primarily affects the lower limb muscles and contributes to gait impairment, COPD is also associated with an increasing risk of falls in patients (COPDp). Previous studies have reported higher rates of falls among COPDp (1.17 to 1.20 falls/person-year), amounting to four times higher than an age-matched healthy group. Potential fall risk factors include muscle weakness, impaired daily activities, cognitive dysfunction, and gait and balance impairment. Although COPDp often manifest many of these risk factors, there remains a gap in literature regarding falls during walking in this population. This study aimed to 1. analyze the literature to identify the risk factors of falling in COPDp, and 2. investigate the underlying mechanisms by which these risk factors can lead to increased prevalence of falling. The results suggest that in addition to the known risk factors of falling, low back pain and mental fatigue should also be considered as relevant risk factors in the treatment process of these patients. Moreover, respiratory problems, which are common in this population, have demonstrated pronounced effects on energy expenditure, gait, and other types of activities of daily living (ADLs), leading to reduced intensity, disrupted coordination of the trunk-pelvic structure with the lower limbs during gait, and altered motor control performance due to activation of muscles in an inefficient synergic manner. These problems potentially lead to the increased vulnerability of these patients to external disturbances and higher incidence risk of falls and injuries. Cognitive problems, which are typically due to reduced oxygen received by the brain, as well as general inflammation caused by COPD, also play a significant role in gait disruption and balance. Future research is warranted to determine the prevalence of falls in COPDp by examining the response of these patients to Medio-Lateral (ML) and Anterior-Posterior (AP) disturbances during gait in association with traditional and recommended fall risk factors.

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., pro-NGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. Besides pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

Selection of appropriate friction factors is paramount for accurate prediction of key flow characteristics in gas–liquid two-phase flows. In this work, experimental investigation of vertical air and oil (with viscosities up to 200 mPa s) flow in a 0.060-m ID pipe is reported. Superficial air and oil velocity ranges utilized are from 22.37 to 59.06 m/s and 0.05 to 0.16 m/s respectively. The influence of estimation of interfacial friction factor on accurate determination of film thickness, void fraction and pressure gradient was investigated using a two-fluid model. The results indicated that the two-fluid model is capable of accurately predicting flow characteristics. Further, it reveals that the best performing correlations are the Belt et al. and Ambrosini et al. correlations.

Both brain-derived neurotrophic factor (BDNF) and glucocorticoids (GCs) have multiple roles in the various aspects of neurons, including cell survival and synaptic function. BDNF and its receptor TrkB express in the central nervous system (CNS) neurons extensively, and contribution of BDNF/TrkB system in neuronal function is evident, thus, its downregulation has been considered to be involved in the pathogenesis of Alzheimer’s disease (AD). GCs, a stress-related molecule, and glucocorticoid receptor (GR) are also considered to be associated with AD, in addition to mental disorders such as depression. Importantly, a growing body of evidence suggest a close relationship between BDNF/TrkB-mediated signaling and GCs/GR system in the CNS. Here, we introduce current studies on the interaction among neurotrophic system and stress in CNS neurons, and discuss their involvement in the pathophysiology of AD.

Lumpy skin disease (LSD) vaccination and epidemiological distribution remain unknown in some parts of Ethiopia including the Sidama regional state. With this, an assessment of LSD vaccine-related problems and serological study was performed in selected districts of Sidama regional state representing three agroecological zones from September 2021 to June 2022. A cross-sectional study of qualitative and quantitative studies was used. The result showed a few portion of respondents know about LSD (29.2%), and vaccinate their cattle (23.3%). 20.8% of the respondents stated LSD occurrence in their vaccinated cattle while focus group discussion with the professionals stated the possible reasons related to electric power disruption that impacted LSD vaccine cold-chain. The other study was on sero-epedimiology of LSD which showed an overall animal and herd level sero-prevalence of 40.8% and 81%, respectively. Higher and lower sero-prevalence was observed in lowland (48%) and highland (28%) areas, respectively. Furthermore, risk factor analysis showed the existence of a significant association between management systems, breed, and body condition score (BCS) of cattle. In conclusion, both qualitative and quantitative study results showed the need for intervention in terms of community-based awareness creation about LSD clinical signs, vaccination advantages, and options for electric power supply together with the frequently updated information on LSD prevalence.

Purpose of this article is to project from the point of view of the scientific data concerning PAF and as a new approach by involving PAF, in order to contribute to clarification and proposal a possible mechanism of action of the coronavirus SARS-CoV-2 and to give a possible explanation for its observed side effects-complications of Covid-19 disease. The article is not intended to suggest any specific drugs, but clarifying the mechanism is the first step in illuminating the direction of prescribing the targets of medication that may be appropriate for the prevention, treatment, and cure of Covid-19 disease. More specifically, the purpose of this article is to provide unequivocal evidence indicating that: 1 It would not be unexpected for PAFR to participate in the entry of coronavirus SARS-CoV-2 into the cell. 2 There is interdependence and relationship of the receptors ACER and PAFR, which means the involvement of PAF in the processes related to coronavirus SARS-CoV-2 as well as to its effects exercised by the coronavirus SARS-CoV-2. 3 The receptors ACER, PAFR and TLRs are also involved in inflammation as well as in virus binding to stabilize and enter into the cell, and so they are "communicating vessels" with PAF being " a missing link" 4 Consequently there is a correlations of COVID-19 disease manifestations and biological characteristics with those caused by PAF, which shows the involvement of PAF in COVID-19 disease.

Huntington's disease (HD) is a rare genetic neurodegenerative disorder that causes motor disorders, neuropsychiatric symptoms and a progressing deterioration of cognitive functions. Complex issues resulting from the hereditary nature of HD, the complexity of symptoms and the concealed onset of the disease have a great impact on the quality of life of family carers. The caregivers are called as “forgotten people” in HD family, also in genetic counseling. This study aims to explore the reliability and validity of the Huntington’s Disease Quality of Life Battery for carers (HDQoL-C) within a Polish population. 90 carers recruited from the Enroll-HD study in Polish research centres of the European Huntington`s Disease Network completed a polish translation of the HDQoL-C. Data was subjected to Principle Components Analysis and reliability measures. The Polish version of the shortened versions of the HDQoL–C is similarly valid compared to the original English version and suitable for use within this population. The HDQoL-C has previously demonstrated a wide range of benefits for practitioners in capturing and understanding carer experience and these benefits can now be extended to Polish speaking populations.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

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

“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, alters tryptophan metabolism with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of IDO induced kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut induced autoantibodies related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. Aldosterone and paroxysmal orthostatic tachycardia syndrome (POTS) paradoxes are highlighted in the context of GPCR and gut dysbiosis, and the role of Candida is explored. The triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

Non-alcoholic fatty liver disease (NAFLD), a frequent complication of metabolic syndrome and visceral obesity, is characterized by marked accumulation of lipids in hepatocytes, accompanied by oxidant stress. In a substantial minority of cases, this progresses to steatohepatitis, which in turn can lead to life-threatening hepatic fibrosis and/or hepatocarcinogenesis. This essay analyzes the molecular biology underlying fat accumulation and oxidant stress in NAFLD, and identifies targets that can be addressed by nutraceutical or dietary measures. Nutraceuticals with potential for prevention or control of NAFLD – as suggested on theoretical grounds, and borne out by experience in rodent studies and/or clinical trials - include ferulic acid, melatonin, methylnicotinamide, tetrahydrocurcumin, nicotinamide riboside, carnosic acid, urolithin A, quercetin, high-dose biotin, citrulline, astaxanthin, long-chain omega-3 fatty acids, berberine, lipoic acid, silibinin, N-acetylcysteine, taurine, capsaicin, spermidine, spirulina, and carnitine. Some of these agents can also address the NLRP3 inflammasome activation and transforming growth factor-β signaling that play a role in driving the transition to steatohepatitis and fibrosis. In addition, soy isoflavones, via estrogen receptor-beta agonism, have anti-fibrotic potential, and supplemental glycine may blunt the contribution of Kupffer cells to the progression of NAFLD. Whole-food plant-based diets of modest protein content, owing to their impact on hormones such as fibroblast growth factor 21 and adiponectin, as well as on the obesity and metabolic syndrome underlying NAFLD, may also be protective in this syndrome. There is considerable potential for complex medical foods or nutraceutical supplementation regimens of rational design to aid prevention and control of NAFLD.

Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, and neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer’s disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on mechanisms behind exercise induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer’s disease pathology. Mechanisms include elevations in peripheral BDNF-inducing hormones such as osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are unclear but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline.

Anastomosing rivers are wetland systems with multiple channels, and there are many constraints limiting in-situ observations of their hydrodynamics. Therefore, there are few reports on the hydrodynamic data of such rivers. In order to obtain the hydrodynamic parameters of the river channels without hydrological observations in the anastomosing rivers, this study proposes an expression method namely expression of channel morphological parameters (ECMP) for hydrodynamic calculations. The calculation formula of the ECMP method based on the shape factor, scale factor, and gradient factor of the flow cross-section as independent variables. This method can be used to calculate the average velocity, discharge, specific stream power, gross stream power and other hydrodynamic parameters of the flow cross-section at different water levels, only requiring the measurement of morphological parameters such as the average depth, width-depth ratio, and gradient of the flow (channel) cross-section. The applicability of the ECMP method was verified using measured hydrological data. The results show that the ECMP method is a practical calculation method with high computational accuracy and convenient application for calculating river hydrodynamic parameters. It has great application value in study on fluvial geomorphology and hydrodynamics, as well as in the reconstruction of ancient river hydrology and hydrodynamics.

Since financial institutions faced to fatal scenario like subprime mortgage crisis and COVID-19, the factor-based asset allocation methodology is noticed. Asset-only approach which make to consider restrictive risk volatility as individual assets had limitation of macro factor risk. For instance, an institution which allocated assets by asset-only approach cannot deal with the inflation crisis. We review the problem of the traditional modern portfolio approach that is used by Korean financial institutions. For reasonable investment of institution, we notice improved factor-based allocation approach. The first result of this paper is that Mean-variance approach as considered only return of asset recorded lower performance than multi factor-based portfolio in macro factor crisis. Second, we notice allocation model which can minimize probability passing the liability risk exposed macro factors to investment risk exposed macro factors. There are three steps in multi-macro factor-based asset allocation approach: discovering macro factors and mapping asset classes to individual macro factor. Second, define liability account and mapping as considering income and pay out of institution. Third, minimize correlation of fac-tor-based asset risk with liability volatility. Furthermore, using covariance return of assets to allocate makes Pareto improvement and supports to break Home-bias problems.

Curcumin is a natural dietary polyphenol which that possesses potent anti-aging and neuroprotective properties through various mechanisms and signaling pathways. This study aimed to investigate the effect of curcumin on factors involved in neurogenesis and angiogenesis in the aged brain. Old female Wistar rats were divided into three equal groups (n=7): control, sham, and curcumin (received curcumin, i.p., 30 mg/kg and 5 days/week for 8 weeks) rats. Curcumin treatment caused a significant increase in the vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF) and anti-apoptotic protein BCl-2 in the brains of aging rats but no significant effect on anti-apoptotic Bax protein. Additionally, curcumin attenuated brain lipid peroxidation and decreased transforming growth factor β1 (TGF-β1). These results suggested that curcumin possesses neuroprotective effects against brain aging, which were mediated by improvment in neurogenesis and angiogenesis. Also, curcumin could alleviate brain aging which may be due to attenuating oxidative stress, inhibiting apoptosis and down-regulating TGF-β1, which in turn enhances VEGF and BDNF. Therefore, curcumin has potential therapeutic value in the treatment of neurological apoptosis, neurogenesis and angiogenesis changes caused by brain aging.

A via ferrata (from the German “klettersteig”, hereinafter VF) is a sports route located on forest and mountains vertical rock walls equipped with steps, chains, artificial dams, bridges and other fixed elements and which have a steel cable (safety cable) all the way along allowing users to secure their progress and avoid possible falls [1]. This article aims to analyse the state of the art of the VF sector in Spain, especially in terms of the regulations of obligatory compliance, in addition to defining the basic characteristics of the installations to ensure that these are safe for users, providing a previously non-existent summary of the most important recommendations regardless of the country where they are installed.

To verify the concept of the metasurfaced reverberation chamber (MRC) which was proposed. This paper reports on measurements in the reverberation chamber (RC) performance by using a 1-bit random coding metasurfaced stirrer. The measurement results are validated and compared with that from two mechanical stirrers (horizontal stirrer and vertical stirrer). Figures of merit such as quality factor (Q factor), number of samples, standard deviation, angle autocorrelation, average K-factor, total scattering cross section (TSCS) and the enhanced back scattering coefficient (eb) are presented. Results indicate the feasibility of the MRC technique in the operation frequency of the RC. And it is possible to enlarge the test volume of the RC by using the 1-bit random coding metasurface stirrer.

This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement to synthesizes the existing literature with a goal to review current conceptual frameworks of mental health of forced migrants for further practice research priorities in social work. The search was done between January 2015 to January 2021. As a result, 29 studies met inclusion criteria. Medicalizing mental health issues by relying solely on the effectiveness of medicine was a controversial risk factor that negatively affected the daily life activities of refugees and reduced their willingness for seeking professional mental health services. Empowering vulnerable minorities by giving them back their power and agency to be able to speak for themselves and raise voices of trauma and recovery was the missing protective factor for sustainable mental health practice. The benefits of group-based interventions are highlighted in which communities and individuals address mental health issues as well as isolation through building collective identities and support networks. Information and communication technologies (ICTs) can add more strength to any kind of mental health intervention. Finally, the benefits of applying ecological perspective for the mental health of refugees, and its implications for a sustainable intercultural practice are discussed. Social workers in this model are the representatives of at-risk groups, thus need more agency and creativity in reflecting client’s concrete needs.

The Rybczynski theorem describes the trade effect within production analyses between factor endowments and outputs. The Stolper-Samuelson theorem focuses on cost analyses between factor reward and commodity price. This paper examines the trade effect of changes of factor endowments on prices, based on general equilibrium. The study shows that changes of factor endowments cause domestic output changes (the Rybczynski effect), which affect output prices and factor prices (the Stolper-Samuelson effect). It is like a chain of effects that the Rybczynski’s trade effect triggers the Stolper-Samuelson’s trade effect. The analysis of this paper shows that a small increase of a factor endowment of any country rewards another factor and the commodity using the latter factor intensively. It displays a tuneful circle. Trade brings a well-balanced development to the world.

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, the metastatic breast cancer leaves a poor prognosis. In an era of personalized medicine, there is an urgent need for a better knowledge of the biology leading to the disease, which can lead to the design of always more accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the Fibroblast Growth Factor Receptor (FGFR) pathway, triggered by specific ligands. The FGFRs/FGFs axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of the FGFRs mutations leading to tumour formation and summarizes the state-of-the-art of therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

CD44 glycoprotein is ubiqutously present and situated at the extracellular surface of cell. Its role as an adhesion recptor was modified depending upon the state of post addition of glycomoeties under varied microenvironment. Many alternative spliced variants of CD44 were expressed by human cells depending upon the attainment during mutifunctional signal disposition. The function of splice factors, and hnRNPA family (Heterogenous ribonucleoproteins A) were dicussed in context to CD44 alternative variants. Glioma cell cline U87 MG were used in this study to search more about the affect of hnRNPA1 and hnRNPA2/B1 knockdown in CD44 V6 and CD44V10 expression. We found in preliminary study that splice factor knock down reduces the alternative splice variants of CD44 such as V6 & V10. Therefore, potential of this study to elaborate further the mechanism in vivo model, to validate the alternative spliced variant in context to interaction with extracellular microenvironment.

Glutathione (GSH) is an antioxidant that our cells utilize to prevent damage done by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals [1]. Due to its immune role in tuberculosis (TB), GSH is hypothesized to play an important part in the immune response against M. tb. Furthermore, one of the hallmark structures of TB is granuloma formation, which involves many types of immune cells. T cells specifically are a major component and are involved in the release of cytokines and activation of macrophages. GSH acts as an important function in macrophages, natural killer cells, and T cells in modulating their activation, their metabolism, the proper cytokine release, the proper redox activity, and free radical levels. For more susceptible patients with HIV and Type 2 Diabetes, the demand for higher GSH levels is increased. This review compiles reports demonstrating the benefits of GSH in improving the immune cell responses against M. tb infection and the use of GSH as adjunctive therapy for TB.

Precipitation gauges are critical for measuring precipitation rates at regional and global scales and are often used to calibrate precipitation rates estimated from other instruments such as satellites. However, precipitation measured at the gauges is affected by gauge-undercatch that is often larger for solid precipitation. In the present work, two popular gauge-undercatch correction factors are assessed: one utilizes a dynamic correction model and is used in the Global Precipitation Climatology Centre (GPCC) Monitoring product and the other one employs a fixed climatology and is used in the Global Precipitation Climatology Project (GPCP) product. How much the choice of correction factors can impact the total estimate of precipitation was quantified over land at seasonal, annual, regional, and global scales. The correction factors are also compared as a function of the environmental variables used in their development, among those are near-surface air temperature, relative humidity, wind speed, elevation, and precipitation intensity. Results show that correction factors can increase the annual precipitation rate based on the gauges by ~9.5 % over the global land (excluding Antarctica), although this amount can vary from ~6.3% (in boreal summer) to more than 10% (in boreal winter), depending on the season and the method used for gauge-undercatch correction. Annual variations of correction factors can also be large, so the use of the fixed climatology correction factors requires caution. Given their magnitudes and differences, selection of appropriate correction factors can have important implications in refining the water and energy budget calculations.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

The continuous development in the field of industrial automation and electric mobility has led to the need for more efficient electrical machines with high power density. The improvement of electrical machines slot filling factors is one of the measures to satisfy these requirements. In recent years, this topic has aroused greater interest in the industrial sector, since the evolution of the winding technological manufacturing processes allows an economically sustainable realization of ordered winding arrangements, rather than random ones. Moreover, the manufacture of electrical machines windings must be preceded by an accurate design phase in which it is possible to evaluate the maximum slot filling factor obtainable for a given wire shape and for its dimensions. For this purpose, this paper presents an algorithmic approach for the evaluation of maximum slot filling factors in electrical machines under ideal geometric premise. In particular, this algorithm has a greater degree of flexibility with respect to the algorithm approaches found in the literature, since the study has been extended to round, rectangular and hexagonal wire sections. Furthermore, the slot filling factor calculation was carried out both for standard and non-standard slots. The algorithmic approach proposed can be considered as an additional useful tool for the fast design of electrical machine windings.

Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.

Zinc, an essential trace mineral, plays a crucial role in over 300 enzymes that are vital for major metabolic pathways. Zinc deficiency can cause various symptoms and sometimes lead to serious conditions, especially after surgery. Therefore, recognising the prevalence and predictors of zinc deficiency before surgery is essential for preventing associated symptoms. Although zinc deficiency is linked to several diseases, its association with orthopaedic disorders remains unclear. This retrospective study aimed to explore the prevalence and predictors of zinc deficiency in orthopaedic inpatients prior to surgery. This retrospective case-control study aimed to investigate the prevalence and predictors of zinc deficiency in orthopaedic inpatients. Patients admitted to the Department of Orthopaedic Surgery at Teikyo University Chiba Medical Center between 15 February 2022 and 31 August 2022 were included. The case-control design categorised patients into zinc deficiency (case) and non-deficiency (control) groups based on serum zinc concentrations (< 60 µg/dL). The data retrieved from the centre’s database included demographics, comorbidities, reasons for hospitalisation, fracture details, medication use, and laboratory values. Statistical tests included Fisher’s exact test for categorical variables and a two-sample t-test for continuous vari-ables. To identify factors associated with zinc deficiency, multivariate analysis ( backward stepwise regression model) was performed for items that were significantly different from the univariate analysis. A total of 156 orthopaedic patients were included in this study. Forty-seven patients (30.1%) had a zinc deficiency. The fracture rate was significantly higher in the case group than in the control group (68.1 % vs. 33.9 %; p < 0.001); spinal disease was significantly less common in the case group than in the control group (2.1 % vs. 31.2 %; p < 0.001); and OA was significantly less common in the case group than in the control group (8.5 % vs. 22.9 %; p = 0.04). The case group had signif-icantly higher rates of fragility and hip and pelvic fractures than did the control group. Spinal disease was less common in the case group than in the control group. Laboratory findings revealed significantly lower mean serum zinc (46.2 µg/dL) in the case group than in the control group (76.3 µg/dL), accompanied by lower albumin and haemoglobin concentrations. Hypoalbuminemia and anaemia were more prevalent in the case group than in the control group. Multivariate logistic regression identified age ≥ 60, anaemia, hip fracture, and hypoalbuminaemia as independent predictive factors for zinc deficiency, while spinal disease was associated with decreased risk. This study identified zinc deficiency in 30.1% of orthopaedic inpatients based on serum zinc concen-trations. Furthermore, age ≥ 60, anaemia, hip fracture, and hypoalbuminaemia were determined as independent predictive factors for zinc deficiency.

IT auditing quality has been defined by results obtained in the process. Meanwhile, multiple studies have been done to enhance it therefore, it continues to be a topic interest and research so it is worth mentioning that its quality relies on trained competent auditors and experts able to develop a process correctly, adapting to clients and to manage auditing inherent risks According to results from the IT audit, low quality and security levels have been identified in terms of the human, technical and contextual factors, affecting audit quality. The objective of this investigation is to identify metrics and to determine their own corresponding factor applying an exploratory type of research. In order to achieve such aim, a targeted survey was designed and implemented at the Institute of Internal Auditors of Ecuador since they have the knowledge and expertise in the field. A factor analysis statistics technique was applied to data gathered to verify that it relates to the identified factors as dimensions are reduced, thus the most impacting metrics may assess the quality of IT audits. Analysis results yielded a mean score for each one of the assessed metrics, concluding that the technical factor is the most significative since it relates roles and task performance during the auditing process as well as control proce-dures. Finally, most auditing quality-related issues are mainly the outcome of an inferior management auditing process, therefore it is crucial that collegiate groups and professionals in the field validate the auditing process.

Background: Dengue incidence has grown dramatically around the world in recent years. It transmitted by Aedes mosquitoes. Many factors contributed to the vector densities such as environmental and sociological factors. Objective: This study is aimed at determining the environmental and sociological factors contributing to dengue cases. Methods: The study used questionnaire survey involving 379 respondent with dengue history. Result: The study showed that there is significant association between the time departs to work and mobility of respondents (95%CI = 2.779 and 5.594, p < 0.0001). Similarly, there is significant association between the time of arrival to work and mobility of respondents (95%CI = 1.617 and 2.155, p < 0.0001). Moreover, the type of housing and the surrounding vegetation were the environmental factors that showed significant values; p = 0.023, and p = 0.017. Conclusion: The study indicated the factors contributed are patient who lived in independent houses and the time of mobility patient.

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

The first FDA-approved drugs were small, chemically-manufactured and highly active molecules with possible off-target effects. After this first successful wave of small drugs, biotechnology allowed the development of protein-based medicines such as antibodies. Conventional antibodies bind a specific protein and are becoming increasingly important in the therapeutic landscape. A very prominent class of biologicals are the anti-TNF drugs that are applied in several inflammatory diseases that are characterized by dysregulated TNF levels. Marketing of TNF inhibitors revolutionized the treatment of diseases such as Crohn’s disease. However, these inhibitors also have undesired effects, some of them directly associated with the inherent nature of this drug class such as immunogenicity, whereas others are linked with their mechanism of action. Recently, researchers tried to design innovative drugs with reduced side effects aiming to make them more effective and safer. Molecules with more specificity e.g. that target one specific TNF format or receptor, or that neutralize the TNF signaling pathway in specific cells, are generated. Alternatively, TNF-directed biologicals without the typical antibody structure are manufactured. Here, we review the complications related to the use of conventional TNF inhibitors, together with the anti-TNF alternatives and the different (neurodegenerative) diseases that might benefit from selective approaches.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

Banana (Musa spp.) is an important crop to the economies of many developing countries. In the north of Argentina, a sub-tropical region, banana plants grow in a suboptimal environment that limits yield because only one harvest per year is achieved. The objective of this work was to characterize the agroecological aptitude of Formosa, Argentina, for banana production, through the behavior of three varieties of international use: Willians, Jafa and Gran Enano, evaluated during five consecutive campaigns. The three-way data analysis technique called Multiple Factor Analysis (MFA) was used for evaluating varieties’ performances across cycles of production. The results allowed inferring the existence of genotype x environment (GEI) interaction, corroborated by two-way factorial ANOVA. In order to determine how this suboptimal environment affects the development of each genotype of this perennial crop, Dual Multiple Factor Analysis (DMFA) was applied to jointly analyze the correlation structure among traits contributing to the performance of each variety at each campaign. The correlation structures between variables were different in each population and varied among campaigns. All traits showed a great variation across years and genotypes, the fruit peel thickness being the most discrepant throughout the campaigns. However, Formosa appeared as a promising subtropical agroecological environment to produce banana because varieties’ performances were acceptable for large scale production systems. In addition to evaluating the adequate aptitude for cultivating banana in Formosa considering the significant effect of GEI, this research makes a methodological contribution by proposing the use of three-way data analysis MFA and DMFA in Agronomy Science.

This study aimed to assess the presence of metal contamination in the sediments of the Narmada River by considering seasonal variations. In this context, samples were gathered from six stations along the river in 2021–22. To assess the various metals including Li, Na, Mg, Al, Ca, Fe, Cu, Zn, Co, and Ni by utilizing ICP-MS. Sediment contamination was assessed by utilizing indices like contamination factor (CF), pollution load index (PLI), geo-accumulation factor (Igeo), and enrichment factor (EF). The observed order of metals concentration revealed that metals Fe>Al>Mg>Ca>Na>Cu>Zn>Co>Ni>Li. The seasonal variation reveals metals Al, Fe, Cu, Zn, and Ni exhibit the highest concentrations during the monsoon and metals Li and Co, the highest concentration in the post-monsoon, while metals Na, Mg, and Ca, exhibit their peak concentration during the pre-monsoon. The findings from CF, PLI, Igeo, and EF indicate that there were low to moderate contaminations, metal pollution exists, uncontaminated to moderate contaminations, and minor enrichment. The cluster analysis revealed the source of contamination was anthropogenic, marine, and fertilizer activities. Additionally, Correlation matrix was employed to establish connections between metals. The findings of this research are to understand the metal contamination and potential carcinogenicity in the sediment of Narmada River.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

Cellular oxidation is responsive to external and internal stimulation and is generated via signal molecules in defense mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Oxidative stress is not necessarily harmful per se; it depends on the balance between oxidation and antioxidation cascades, which are induced according to stimuli and can maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and ROS production, using IV as an example. We introduce the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS production and various effects of IV infection. We also summarize the potential anti-IV agents that act by targeting oxidative stress.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

Most of the damage to Vleg cars was caused by material fatigue. The objectives of the fatigue analysis on Xenia 2011 car wheels with the Finite Element Method using Solidworks are: 1) Knowing the fatigue analysis process on car wheels, 2) Knowing the results of the fatigue analysis on car wheels. The research method used is the Finite Element Method (FEM) method; the re-search steps include model data retrieval from the Wheel code, 3D model creation process, static simulation process according to SAE J 328 standard, mesh variations, fatigue simulation, and finally, standardization of results fatigue simulation regarding the SAE J 328 standard. The re-sults of the fatigue analysis on the Xenia 2011 car wheels obtained an age of 1000,000 cycles when compared with the minimum average of SAE J 328 of 600,000 cycles, this product design is clas-sified as a high cycle, which means it will experience a prolonged failure, and this design has a maximum alternating stress value of 627.4702 MPa, a strain of 0.007105, a displacement of 7.148 mm and a SOF of 0.087890 with a load factor used of 2.5, so overall this Xenia car can be loaded with a load of 1775 kg, if it is more than that, then Wheels will experience cracking.

The Lin28B gene is involved in the initiation of puberty, but its regulatory mechanisms remain unclear. Therefore, in this study, we aimed to study the regulatory mechanism of the Lin28B promoter by cloning the Lin28B proximal promoter for bioinformatics analysis. Next, a series of deletion vectors were constructed based on the bioinformatics analysis results for dual-fluorescein activity detection. The transcriptional regulation mechanism of the Lin28B promoter region was analyzed by detecting mutations in transcription factor-binding sites and overexpression of transcription factors. The dual-luciferase assay showed that the Lin28B promoter region -837 to -338 bp had the highest transcriptional activity, and the transcriptional activity of the Lin28B transcriptional regulatory region decreased significantly after Egr1 and SP1 mutations. Overexpression of the Egr1 transcription factor significantly enhanced the transcription of Lin28B, and the results indicated that Egr1 and SP1 play an important role in regulating Lin28B. These results provide a theoretical basis for further research on the transcriptional regulation of sheep Lin28B during puberty initiation.

Background: Currently, completed suicide, suicide ideation, suicide behavior, and suicide attempts are major public health problems worldwide. Major Depressive Disorder (MDD) is one of the most common mental disorders associated with an increased risk of suicide. Since the relationship between suicide and cholesterol levels is still controversial, in this study, we explore the association between SNPs rs754203 and rs4900442 of CYP46A1 with suicide risk in Mexican patients with major depressive disorder. Methods: We evaluated 188 unrelated suicide completers and compared them to 144 non-suicidal individuals (controls) and 126 MDD patients. Genotypes were analyzed using the Real Time-polymerase chain reaction method and two allele-specific probes to detect specific SNP targets. A chi-square test was used to identify a possible risk genotype or allele type for suicide. Results: Statistical analysis showed significant differences between completed suicide and controls in their allelic and genotypic frequencies in rs754203 SNP. The genotype G/G of CYP46A1 rs754203 was significantly associated with suicide. Also, the G allele was associated with an increased risk of suicide (OR= 1.370, 95% CI= 1.002-1.873). No differences in either genotype distribution or allele frequencies of CYP46A1 rs4900442 were observed. Conclusions: The results of the current study report the first association between G allele carriers (A/G + G/G) of rs754203 and increased risk for suicide, especially in males.

The purpose of this paper is to develop an index system for measuring the compliance of high-rise residential buildings with fire requirements and also to develop an index system for measuring the fire response efficiency, which is linked to the index of compliance with fire requirements. The higher the compliance rate, the greater the chance of a successful response. The two systems de-pend on the automation of the firefighting system management processes using the techniques of the fourth industrial revolution and developed based on the consultation of subject matter experts in the field. The main elements of the indexes were identified, which were based mainly on several variables, including the fire administrative system, the firefighting system, the residents, the loca-tion of the high-rise residential buildings from the fire extinguishing station, and the height of the high-rise residential building. The two systems can contribute to improving emergency prepared-ness in high-rise residential buildings in the Emirate of Sharjah and are also considered as a measurement index for compliance with fire requirements in the Emirate of Sharjah.

Every year around 800 000 people commit suicide, this represents one death every 40 seconds. In the search for possible biological biomarkers associated with suicide and/or psychiatric disorders, serum cholesterol levels have been extensively explored. Several studies have indicated that cholesterol and associated proteins, especially apolipoproteins (Apos), may play an important role in the diagnosis, prognosis, and susceptibility of suicide. Here, we describe the current knowledge and findings in the relationship between apolipoproteins and suicide.

Salmonella enterica serovar Newport bacteriophage 7-11 shares 41 homologous ORFs with Escherichia coli phage phiEco32 and both phages encode a protein similar to bacterial RNA polymerase promoter specificity  subunit. Here, we investigated the temporal pattern of 7-11 gene expression during the infection and compared it to the previously determined transcription strategy of phiEco32. Using primer extension and in vitro transcription assays we identified eight promoters recognized by host RNA polymerase holoenzyme containing 7-11  subunit SaPh711_gp47. These promoters are characterized by a bipartite consensus GTAAtg-(16)-aCTA and are located upstream of late phage genes. While dissimilar from single-element middle and late promoters of phiEco32 recognized by holoenzyme formed by the phi32_gp36  factor, the 7-11 late promoters are located at genome positions similar to those of phiEco32 middle and late promoters. Two early 7-11 promoters are recognized by RNA polymerase holoenzyme containing host primary σ70 factor. Unlike the case of phiEco32, no shut off of σ70-dependent transcription is observed during 7-11 infection and there are no middle promoters. These differences can be explained by the fact that phage 7-11 does not encode a homologue of phi32_gp79, an inhibitor of host and early phage transcription and an activator of transcription by the phi32_gp36-holoenzyme.

The article discusses the issues related to the safety of transport of dangerous goods by road. Research on accidents in transport unambiguously points to the human factor, which is most responsible for causing the accident. Determining the causes of driver unreliability in the hu-man-vehicle-environment system requires thorough research. Unfortunately, in this case, experimental research with human involvement is limited in scope. This leaves modeling and simulation of the behavior of the human factor, i.e., the driver transporting dangerous goods. The human being, due to its complexity, is a challenging element to parameterize. The literature presents various attempts to model human actions. In their work, the authors used heuristic methods, specifically fuzzy set techniques, to build a human factor model. In these models, human actions were specified using a verbal or linguistic description. The specificity of fuzzy sets allows to "naturally" limit the "precision" in describing human behavior. The model was built based on the author's questionnaire and expert research, based on which individual features were selected. Then, the traits were assigned appropriate states. The output parameter of the model is λL - the intensity of human error. The obtained values of the intensity of the accident caused by the driver's error were implemented into the author's method of risk assessment. They constituted one of the factors determining the probability of an accident in the transport of dangerous goods, which allowed to determine the optimal route of transport of these goods characterized by the lowest risk of an undesirable event on the route. The article presents the model's assumptions, structure, and features included in the model, which have the most significant influence on shaping the intensity of human error. The results of the simulation studies showed a diversified effect of the analyzed characteristics on the driver's efficiency.

We are using information from a paper deriving a Lorentz-violating energy-momentum relation entailing an exact mo_mentum cutof as stated by G. Salesi . Salesi in his work allegedly defines Pre Planckian physics, whereas we restrict our given application to GW generation and DE formation in the first 10^-39s to 10^-33s or so seconds in the early universe. This procedure is inacted due to an earlier work whereas referees exhibited puzzlement as to the physical mechanism for release of Gravitons in the very early universe. The calculation is meant to be complementary to work done in the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, and also a calculation for Black hole destruction as outlined by Karen Freeze, et. al. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes but we claim that this destruction is directly linked to a Lorentz violating energy-momentum G. Salesi derived, which we adopt, with a mass m added in the G. Salesi energy momentum results proportional to a tiny graviton mass, times the number of gravitons in the first 10^-43 seconds

Annually, millions of people (including children) across the world face minor to severe impact from natural or human-induced disasters. Diverse models have been conceptualized and adopted at global scale to increase resiliency of children from disasters focusing on preparedness, response and recover. As children spend most of their lives at school or at home, this paper discusses on factors contributing towards improving or degrading resiliency of children from disasters. Giving low priority to institutional resilience, this paper highlights the behavioral aspects of children which becomes their strength on demonstrating appropriate practices to mitigate disaster risks on self at school, home and community. While doing so, attributes from Ajzen’s Theory of Planned Behavior has been linked with the components of resilience to explain the causative factors. Adopting desk review, this paper describes behavioral attributes of children and emphasizes on need of having multi-dimensional framework to enhance resiliency of children.

A technique devised some years ago permits to study a theory in a regime of strong perturbations. This translate into a gradient expansion that, at the leading order, can recover the BKL solution. We solve exactly the leading order equations in a spherical symmetric case and we show that the 4-velocity in such a case is multiplied by an exponential warp factor when the perturbation is properly applied. This factor is always greater than one. We will give a closed form solution of this factor for a simple case. Some numerical examples are also given.

Ageing may be characterized by progressive loss of cognitive function as well as decrease in physical activities, in addition to change in appearance. Previously, we reported that intracerebroventricular transplantation of a human neural stem cell (NSC) line (F3) over-expressing choline acetyltransferase (F3.ChAT) gene, an enzyme responsible for acetylcholine synthesis, markedly improved cognitive function and physical activity of aged animals by enhancing acetylcholine and growth factors (GFs) and neurotrophic factors (NFs). In the present study, 10-month-old F344 rats were intravenously transplanted with F3 or F3.ChAT NSCs (1 x 106 cells) once a month to 21st month of age when the cumulative mortality reached 20%, and physical activity and learning/memory function were investigated, in addition to the analyses of brain acetylcholine concentration, and cholinergic and dopaminergic system restoration. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both the cognitive (passive avoidance and water-maze performances) and physical (locomotor and rota-rod activities) functions, in parallel with the elevation of acetylcholine levels in cerebrospinal fluid and in muscles, in which F3.ChAT cells were superior to F3 parental cells. Stem cell transplantation down-regulated CCL11, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, and preserved brain and muscular capillaries, recovering muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage of multiple organs including muscles and the brain. The results indicate that NSCs over-expressing ChAT gene improve cognitive function and physical activity of ageing animals by protecting and recovering functions of multiple organs including cholinergic and dopaminergic systems as well as muscles from oxidative injuries through secretion of acetylcholine and GFs/NFs, increased antioxidant elements, and enhanced blood flow.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

Ral-interacting protein 76 (RLIP76) is a potential factor with vascular endothelial growth factor (VEGF) in the corpus luteum and tumor angiogenesis. RLIP76, VEGF, and hypoxia-inducible factor-1 (HIF-1) are proteins that activate angiogenic functions in tumor and endothelial cells. RLIP76 is a main factor in tumor growth, and VEGF is a major endothelial cell protein for angiogenesis. Also, RLIP76 regulates a small GTPase (R-Ras, oncogene) in cell survival, spreading, and migration. HIF-1 is important in the corpus luteum, tumor angiogenesis, and tumor growth. VEGF and HIF-1 regulate the angiogenic function of RLIP76, and RLIP76 controls vascular growth in endothelial and tumor cells. RLIP76, R-Ras, VEGF, and HIF-1 may be useful in the research of corpus luteum and cancer therapy and the study of mechanisms of tumor angiogenesis. This review will help to elucidate the roles of RLIP76/R-Ras and VEGF via HIF-1 in corpus luteum and tumor angiogenesis, tumorigenesis, and the specific regulation of RLIP76 in luteal, tumor, and endothelial cells. Thus, we reviewed the angiogenesis of the corpus luteum and tumor in the ovarian and tumor microenvironment.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

Jujube (Ziziphus jujuba Mill.) stands as a pivotal fruit tree with significant economic, ecological, and social value. Recent years have witnessed remarkable strides in multi-omics-based biological re-search on jujube. This review began by summarizing advancements in jujube genomics. Subse-quently, we provided a comprehensive overview of the integrated application of genomics, tran-scriptomics, and metabolomics to explore pivotal genes governing jujube domestication traits, quality attributes (including sugar synthesis, terpenoids, and flavonoids), and responses to abiotic stress, and discussed the transcriptional regulatory mechanisms underlying these traits. Further-more, challenges in multi-omics research on jujube biological traits were outlined, and we pro-posed the integration of resources such as pan-genomics and sRNAome to unearth key molecules and regulatory networks influencing diverse biological traits. Incorporating these molecules into practical breeding strategies, including gene editing, transgenic approaches, and progressive breeding, holds the potential for achieving molecular-design breeding and efficient genetic en-hancement of jujube.

This study aimed to examine the association of blood triglyceride levels with fasting blood glucose levels and type 2 diabetes (T2D) prevalence in Chinese adults with normal triglyceride levels (<1.7 mmol/L), using linear regression and binary logistic regression, respectively. This cross-sectional study included 16,706 Chinese adults, among which 1,067 had T2D. Triglycerides were positively associated with fasting plasma glucose after multivariate adjustment (β=0.034, P<0.001). One natural log unit increase in blood triglycerides was associated with a 61% higher multivari-ate-adjusted risk of T2D (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.19-2.17; P=0.002). The positive associations remained when participants who were treated with lipid-lowering or an-ti-diabetic drugs were excluded. The optimal cut-off of triglycerides for T2D was 1.09 mmol/L (obtained using Receiver Operating Characteristic curve analysis). Participants with triglycerides of ≥1.09 mmol/L had a 28% higher risk of T2D (OR, 1.28; 95% CI, 1.07-1.53; P=0.006) compared to those with triglycerides below the cut-off. In conclusion, this study showed that, in people with normal triglyceride levels, triglycerides at the upper normal range correlated with increased T2D diagnosis risk, with an optimal cut-off of 1.09 mmol/L. Therefore, adults with high “normal” triglyceride levels (1.09-1.69 mmol/L) may need to be closely monitored for the development of T2D.

The Myb family of transcription factors (TFs) is a large and functionally diverse group found in all eukaryotes, but its role in fungi remains poorly understood. Here, we characterized a Myb family TF called MoMyb13 in the rice blast fungus, Magnaporthe oryzae. MoMyb13 has two Myb domains and has orthologues only in ascomycete fungi. Localization experiments confirmed that MoMyb13 is located in the nuclei, as expected for a TF. Phenotypic analysis showed that MoMyb13 mutants exhibited reduced growth, whitened colony appearance and no conidia formation. Importantly, these mutants completely lost pathogenicity, despite being able to form appressoria at their hyphae ends, suggesting that these appressoria were non-functional for causing infection. Furthermore, the mutant colonies lost hydrophobicity and had significantly reduced expression of the hydrophobin MPG1. However, overexpression of MPG1 in the mutants restored their hydrophobicity, but not pathogenicity. Stress assay showed that the mutants were more sensitive to SDS, CR and H2O2, but more tolerant to NaCl and SOR. In summary, our study revealed the essential role of the MoMyb13 in the growth, conidiation, hydrophobicity, stress response and pathogenicity of M. oryzae, and provides valuable insights into the working mechanism of Myb TFs in fungi.

This paper undertakes an in-depth exploration of a primary strategy aimed at mitigating the volumetric risk in wind power generation within Greece, which originates from the variability of wind speeds. The proposed strategy hinges on portfolio theory, serving as the foundation for creating diverse generation portfolios, thus facilitating the strategic distribution of available capacity across space. Optimization techniques and quadratic programming are harnessed to derive the minimum variance portfolio along with alternative optimal allocation plans. In parallel, Factor Analysis techniques are deployed to discern prevalent sources of variability that exert influence on wind generation dynamics within Greece. Our assessment encompasses an appraisal of the diversification efficacy inherent in an array of distinct portfolios. This analysis is conducted through the application of Principal Component Analysis (PCA) techniques. Furthermore, we expound upon key spatiotemporal attributes characterizing the Greek landscape, elucidating their potential contributions to the site-selection process.

Sweetpotato is an important miscellaneous grain crop in China, which is threatened by a variety of diseases and insect pests in the process of cultivation and production. sweetpotato stem rot is one of the common sweetpotato diseases, which seriously affects the yield and quality of sweetpotato. However, there are few studies on the mechanism of resistance to stem rot in sweetpotato. In this study, transcriptome sequencing analysis was carried out on the samples at different stages (T1, T2, T3) of stem rot pathogen infecting Xushu 48, and 44839 (T1-VS-T2), 81436 (T1-VS-T2) and 61932 (T2-VS-T3) differentially expressed genes (DEGs) were obtained. The DEGs were mainly concentrated in Alanine, aspartate and glutamate metabolism (ko00250), Carbon fixation in photosynthetic organisms (ko00710) and Amino sugar and nucleotide sugar metabolism (ko00520) and some candidate genes related to plant pathogen infection, such as receptor-like protein kinase (RLK5, RLK7), LRR receptor-like serine/threonine-protein kinase (SERK1), bHLH137, ERF9, MYB73 and NAC053, were screened. The results of this study provide genetic resources for the research on stem rot resistance of sweetpotato and provide theoretical basis for sweetpotato resistance breeding.

: Background: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcriptional factor nuclear factor κB (NFκB) is activated by cytokines, such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NFκB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NFκB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. Materials and Methods: Evaluation of safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSCh) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover. The efficacious concentration of Decoy determined from the rNSCh was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the level of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. Results: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life 63% and decreasing matrix metalloprotease 3 (MMP3) by 70.7% (P = 0.027). Conclusions: Decoy may be a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

This article presents a new design of supporting tethers through the concept of force distribution. The transmitted force applied on tethers will be distributed on the new tether design area resulting in low acoustic energy transferred to anchor boundaries and stored energy enhancement. This technique achieves an anchor quality factor of 175,000 compared to 58,000 obtained from con-ventional tether design representing 3-fold enhancement. Also, the unloaded quality factor of the proposed design improved from 23,750 to 27,442 representing 1.2-fold improvements.

bZIP transcription factors, basic leucine zipper, play significant roles in plants’ growth and development processes, as well as in response to biological and abiotic stress. Hypericum perforatum is one of the world's top three best-selling herbal medicines, mainly used to treat depression. However, there is no systematic identification or functional analysis of the bZIP gene family in H. perforatum. In this study, 79 HpbZIP genes were identified. Based on phylogenetic analysis, the HpbZIP gene family was divided into ten groups, designated A-I, and S. The physicochemical properties, gene structures, protein conserved motifs, and Gene Ontology enrichments of all HpbZIPs were systematically analyzed. The expression patterns of all genes in different tissues of H. perforatum (root, stem, leaf, and flower) were analyzed by qRT-PCR, revealing the different expression patterns of HpbZIP under abiotic stresses. HpbZIP69 protein is localized in the nucleus. According to the results of the yeast one-hybrid (Y1H) assays, HpbZIP69 can bind to the HpASMT2 (N-Acetylserotonin O-methyltransferase) gene promoter ( G-box cis-element ) to activate its activity. Overexpressing HpbZIP69 transgenic Arabidopsis lines enhanced tolerance to drought. The content of MDA and H2O2 content was significantly decreased, and the activity of superoxide dismutase (SOD) was considerably increased under the drought stress. These results may aid in additional functional studies of HpbZIP transcription factors and cultivating drought-resistant medicinal plants.