In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. Conclusions: From a regulatory perspective, D-mannose maintains the current medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

Age-related declines in vitamin D receptor (VDR) expression have been implicated in the onset of sarcopenia. The increased expression of VDR in muscle is known to increase muscle mass, whereas VDR knockout in the muscle decreases muscle mass in rats. Similar to VDR, the age-related decline in protein deacetylase sirtuin (SIRT) expression is linked to the development of sarcopenia and age-related muscle dysfunction. This study aimed to investigate whether the VDR agonist 1,25-dihydroxyvitamin D3 (1,25VD3) exerts beneficial effects on muscles through interactions with sirtuins and, if so, the underlying molecular mechanisms. 1,25VD3 treatment increases the expression of VDR, SIRT1, and SIRT3 in C2C12 myotubes. Additionally, it stimulates the differentiation of C2C12 myoblasts into myotubes. Furthermore, 1,25VD3 significantly enhanced the expression of key myogenic markers, including myosin heavy chain (MyHC) proteins (MyHC I and II), MyoD, and MyoG, and increased the phosphorylation of AMPK and AKT. Conversely, VDR knockdown in myoblasts induces myotube atrophy by downregulating SIRT1 and SIRT3 expression. Furthermore, 1,25VD3 ameliorated muscle atrophy and apoptosis induced by IFN-γ/TNF-α co-treatment to C2C12 myotube. Moreover, 1,25VD3 downregulated the increased expression of muscle atrophy-associated proteins, including FoxO3a, MAFbx, and MuRF1 in IFN-γ/TNF-α induced atrophy model. Importantly, IFN-γ/TNF-α significantly reduced the mtDNA copy number in C2C12 myotube, whereas the presence of 1,25VD3 effectively prevented this decrease. These results indirectly suggest that 1,25VD3 has the potential to develop as a therapeutic or preventive agent for age-mediated muscle atrophy by enhancing the VDR/SIRT1/SIRT3 axis and inhibiting the FoxO3-mediated atrophy pathway.

The purpose of this research was two-fold: (a) to observe whether highly trained adolescent swimmers abide to vitamin D supplement recommendations; and (b) to monitor changes in circulating 25-hydroxyvitamin D (25(OH)D) that occur between the autumn and winter months. Twenty swimmers (age: 17 ± 2 years) from a UK high-performance swimming club volunteered to complete two blood spot cards to determine 25(OH)D concentration: the first in an autumn training phase (October) and the second during winter training (January). All swimmers were advised to consume vitamin D3 supplements across the assessment period; however, only 50% of swimmers adhered to this recommendation. Resultantly, a winter decline in 25(OH)D was observed in non-supplementing swimmers (79.6 ± 25.2 to 52.6 ± 15.1 nmol·L-1, p = 0.005), with swimmers either displaying an ‘insufficient’ (60%) or ‘deficient’ (40%) vitamin D status. In comparison, greater maintenance of 25(OH)D occurred in supplementing swimmers (92.0 ± 25.5 to 97.2 ± 38.3 nmol·L-1, p = 0.544), although variable outcomes occurred at the individual level (four increased, three maintained, three declined). These findings highlight possible risks of vitamin D insufficiency during the winter for swimmers in the UK, possibly requiring standardised supplement practices. Moreover, alternative educational strategies may be required for swimmers to transfer knowledge to practice in order to improve supplement adherence in future.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

Controlling water and food contamination by pathogenic organisms requires quick, simple, and low-cost methods. using affinity between mannose and type I fimbriae in the cell wall of Escherichia coli bacteria as evaluation elements compared to the conventional plate counting technique enables a reliable sensing platform for the detection of bacteria. In this study, a simple new sensor based on electrochemical impedance spectroscopy (EIS) for rapid and sensitive detection of Escherichia coli was developed. Biorecognition layer of the sensor was formed by covalent attachment of p-carboxyphenylamino mannose (PCAM) to gold nanoparticles (AuNPs) electrodeposited on the surface of glassy carbon electrode (GCE). The resultant structure of PCAM was characterized and confirmed using FTIR. The developed biosensor demonstrated a linear response with a logarithm of bacterial concentration (R2 = 0.998) in the range of 1.3 × 10 1~ 1.3 × 106 CFU.mL−1with the limit of detection of 2 CFU.mL−1 within 60 min. The sensor did not generate any significant signals with two non-target strains, demonstrating high selectivity of the developed biorecognition chemistry. Selectivity of the sensor and its applicability to analysis of the real samples was investigated in samples of tap water. Overall, the developed sensor has shown to be promising for the detection of E. coli pathogen in water due to its high sensitivity, short detection time, low cost, high specificity, and user-friendliness.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

D-Serine, a co-agonist of NMDA receptors has sparked a contentious debate within the scientific community regarding its status as a gliotransmitter or a neurotransmitter. This comprehensive review delves into the heart of this debate, offering a meticulous analysis of the existing evidence from various research methodologies. Immunostaining studies and cell-selective mutations provide compelling support for D-serine's neuronal origin, bolstering the serine shuttle model. In contrast, the gliotransmission hypothesis, proposing astrocytic synthesis and release, faces critical scrutiny as inconsistencies in supporting data emerge. In vivo microdialysis experiments unveil a neuronal contribution to D-serine release and its profound impact on synaptic plasticity, further strengthening the case for neuronal dominance. Counterarguments in favor of astrocytic D-serine release are systematically dissected, revealing inherent limitations and ambiguities. Collectively, the evidence corroborates D-serine's neuronal source and discounts the astrocytic hypothesis. This review underscores the need for scientific rigor when evaluating contentious topics and affirms the simplicity of the neuronal explanation, aligning D-serine with the serine shuttle model, thus advancing our comprehension of its pivotal role in synaptic function and cognitive processes. As the debate continues to evolve, this exploration encourages ongoing research to unravel the intricate mechanisms governing D-serine neurotransmission.

Cellulose nanocrystals (CNCs) are a kind of nano-inclusions that have experienced tremendous expansion in the material industry due to their outstanding mechanical qualities, sizable surface area, and capacity for functional tuning. Due to their vast potential, however, present practises fall short of fully using them. For example, employing CNCs in various matrices with various surface chemistries can be challenging; this problem tends to get worse if the focus is furthered on bio-based applications. This paper reviews the use of CNCs as fillers in natural and man-made polymers; we have explored in depth the production, characterisation, and of CNCs from various sources and their inclusion into various matrices. Surface alterations and the introduction of CNCs in biodegradable polymer can have a significant impact on several industrial behemoths such as tissue engineering and biomedical applications; therefore, pursue of current manuscript is extremely warranted. Throughout the manuscript various assembly techniques that involves alteration and adjustment of polymer network in building up a hydrogel with higher fracture energy and mechanical properties are also included. From rheological perspective the hydrogel processing is also discussed with some models routinely used in the literature to describe these hydrogels. Finally, bio-based hydrogels mechanically reinforced with CNCs such as Xanthan Gum, Alginate, protein, and polysaccharides were discussed.

The InSAR technique measures the displacement of an indicator using SAR image interference. The technique of interfering two SAR images among InSAR techniques is called Differential InSAR (D-InSAR). In the process of D-InSAR, the filtering technique is used in the Unwrapped Mask, usually using the GoldStein method. However, since the Goldstein method removes the noise on the path, it is difficult to derive the displacement value in the agricultural area where the relative coherence is low. In Korea, more than 50% of the whole country consists of mountainous regions and agricultural regions, so it is difficult to use the Goldstein technique polysynthetically. In this study, we set the test-bed for the urban area and the agricultural area based on Coherence, and introduce Goldstein and Boxcar Filter, one of the Goldstein and LSM techniques. Through this process, we want to draw the conclusion which is displacement values ​​in the agricultural area.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p<0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

Chronic oxidative stress in long-distance runners adversely affects conditioning. Therefore, it is important to objectively assess and monitor oxidative stress but measuring oxidative stress can be invasive or require skill to measure. Therefore, this study aimed to verify whether skin autofluorescence (SAF), a noninvasive, rapid, and easily calculable metric for calculating advanced glycation end products (AGEs), is useful as an oxidative stress biomarker. The subjects were 50 young Japanese male long-distance runners (aged 20.2 ± 1.2 years); 35 average male university students (aged 19.8 ± 1.1 years) served as controls. The interactions and relationships between SAF and plasma pentosidine and oxidative stress markers (reactive oxygen metabolite-derived compounds [d-ROMs], biological antioxidant potential [BAP], and the BAP/d-ROMs ratio) in runners were examined, and SAF in the runners and controls was compared. The results suggest that plasma pentosidine in runners is associated with oxidative stress markers and that plasma pentosidine can assess oxidative stress. However, SAF was not validated as an oxidative stress marker because it was not associated with oxidative stress marker. In future, clarifying the factors affecting SAF may clarify the relationship between SAF, plasma pentosidine, and oxidative stress markers.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

This paper introduces PatchFusion, an innovative approach for nonrigid tracking and reconstruction of deformable objects using a single RGB-D sensor. Existing methods face challenges in accurately capturing the rapid deformations of soft and flexible objects, thereby limiting their utility in diverse scenarios. Our approach overcomes this challenge by employing a dynamic patch-based framework that adapts to rapid inter-frame motions. Firstly, patch-wise rigid transformation fields for non-overlapping patches are solved via Iterative Closest Point (ICP) by incorporating geometric features as additional similarity constraints, thereby enhancing robustness and accuracy. Secondly, deformation optimization based on a nonrigid solver is applied to refine the coarse transformation fields. In order to enable simultaneous tracking and reconstruction of deformable objects, the patch-based rigid solver is designed to run in parallel with the nonrigid solver, serving as a plug-and-play module requiring minimal modifications for integration while enabling real-time performance. Following a comprehensive evaluation, PatchFusion showcases superior performance in effectively dealing with rapid inter-frame deformations when compared to existing techniques, rendering it a promising solution with broad applicability across domains such as robotics, computer vision, and human-computer interaction.

This review examines the challenges faced by the pig industry, with a specific emphasis on improving the health and growth of weaned pigs. It emphasises the immediate necessity of investigating alternative approaches to managing pig nutrition and health due to restrictions on the use of antibiotics and the prohibition of zinc oxide in weaned pig diets. The weaning phase is identified as a critical stage in piglet development, characterized by stressors that affect their gastrointestinal health, immune responses, and overall physiology. The primary challenge during weaning arises from transitioning piglets from a digestible milk-based diet to a less digestible cereal-based feed, causing nutritional stress. This manifests as reduced feed intake, leading to gastrointestinal disturbances, intestinal inflammation, and adverse effects on intestinal structure and microbiota. To address these challenges and optimise piglet development, various nutritional strategies have been explored. Notably, glucans, particularly β-glucans from fungi, cereals, algae, and yeast, show promise in alleviating weaning-related issues. Furthermore, it's important to highlight the critical roles played by vitamin D and selenium in piglet nutrition. These essential nutrients can be sourced naturally from enriched mushrooms that are specifically enriched with vitamin D and selenium, providing a valuable dietary option. In conclusion, effective nutritional strategies, including glucans, vitamin D, selenium, and enriched mushrooms, are beneficial for addressing weaning-related challenges.

Under the guidance of our previous achievements, and in order to extend this small molecular library. In current work, other 21 novel structures of thieno[2,3-d]pyrimidines containing isoxazole-moiety (1a-1u) were firstly synthesized and the cytotoxicity to A549, HCT116 and MCF-7 cell lines was evaluated using the MTT method. The results showed that most target compounds exhibited good to excellent cytotoxicity to A549, HCT116 and MCF-7 cell lines, especially 6-Methyl-4-{[3-(4-chlorophenyl)-isoxazol-5-yl-]-methoxy-}-thieno[2,3-d]-pyrimidine (1e) exhibited a broad-spectrum and the most potent cytotoxicity to A549, HCT116 and MCF-7 cell lines (IC50s: 2.79, 6.69 and 4.21×10^-3 μM, respectively) as compared with the reference drug gefitinib (IC50s: 17.90, 21.55 and 20.68 μM, respectively). 1e can be seen as the best drug candidates for development of anticancer drugs.

At-home rapid antigen test (RAT) kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are valuable public health tools during the present coronavirus disease (COVID-19) pandemic. They provide fast identification of coronavirus infection, which can help to reduce the transmission rates and burden on the healthcare system. However, they have lower sensitivity when compared with the reverse transcription polymerase chain reaction (RT-PCR) tests. One of the reasons for the lower sensitivity is due to the RAT color indicators being indistinct or invisible to the naked eye after the measurements. For this reason, we propose a systematic approach, through which we investigated anonymously provided at-home RAT kit results by using our in-house open source image processing scripts developed for affordable Raspberry Pi computer and Raspberry Pi HQ camera systems (available at https://github.com/kmiikki/ratcv). Therefore, we aimed at minimizing the human-related analysis errors for such kits. We believe that our framework can contribute to reduced the delayed quarantines of infected individuals and spreading of the current infectious disease.

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2),and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK 3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3 and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspase and GSK3β

Coronavirus Disease 2019 (COVID-19) exhibits a significant variation in presentation of symptoms ranging from mild to severe life-threatening symptoms, including death. COVID-19 infection susceptibility has been linked with various covariates, but studies in Qatar are limited. Data from Qatar Biobank (QBB) (n = 10,000; 18- to 79-year-old adults) were analyzed for associations between sociodemographic and lifestyle factors and susceptibility to COVID-19. Logistic regression was used to assess the associations between COVID-19 and age, gender, body mass index (BMI), smoking status, education level, dietary patterns, supplement use, physical activity, history of bariatric surgery, diabetes, and hypertension. In total, 10.5% (n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR]= 0.55; 95% CI: 0.44-0.68 and OR= 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction of the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥30 kg/m2), history of bariatric surgery and higher adherence to the modern dietary pattern– characterized by consumption of foods high in saturated fat and refined carbohydrates– were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The investigation involves the utilization of molecular modeling and computational chemistry tools, with a specific focus on Conceptual DFT. These techniques are applied to examine the chemical reactivity of Talarolide A and Talaropeptides A-D, shedding light on their potential for interacting with various biological targets. The research reveals insights into the chemical reactivity of Talarolide A and Talaropeptides A-D, uncovering active reaction sites and potential biological targets. Talarolide A demonstrates robust anti-inflammatory properties and antitumor activity against diverse cancer cell lines, while Talaropeptide A displays antimicrobial efficacy against both bacteria and fungi. The study underscores the significance of comprehending the chemical reactivity of natural marine products for advancing pharmaceutical development. By employing computational tools such as Conceptual DFT, this research uncovers crucial information about the active sites and potential targets of Talarolide A and Talaropeptides A-D. The findings contribute to the broader understanding of marine-derived peptides and their prospects as pharmaceutical agents, though further investigations are necessary to fully elucidate their pharmacological attributes.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Background/Aim: Rapid onset of facial ptosis can impact physical appearance and compromise the outcomes of facelift procedures. The level of vitamin D has a potential correlation with collagen formation and its deficiency with inflammatory processes that affect the breakdown of hyaluronic acid. This study aims to investigate the potential relationship between accentuated facial ptosis in women and low levels of vitamin D. Furthermore, it aims to explore preventive measures or strategies to slow down facial ptosis and enhance the longevity of facelift results. Materials and Methods: The study was focused on monitoring the vitamin D levels in women and men with advanced facial ptosis and comparing them with a control group. Results: Notably, a direct association between gender and serum vitamin D levels was observed, indicating less sustainable outcomes in women. Conclusion: Women face additional challenges in the aging process due to hormonal shifts after menopause or premenopausal, which are associated with osteoporosis and lower vitamin D levels.

(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: to achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3,704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.

This research aims to obtain empirical evidence of the influence of the masculinity of male CEOs on the of research & development, this research seeks to identify the influence of the face of mas-culinity of male CEO’s on the of research & development. The study used a quantitative approach with population and research samples using companies listed on the Indonesia Stock Exchange from 2016 to 2021. The study collected images of faces identified as male CEOs from data from the Indonesia Stock Exchange website and company as utilizing Google searches. The data analysis method in this study used Regression Ordinary Least Square (OLS) with Stata Software. Stata software is one of the regression completion procedures that has a high degree of flexibility in re-search that connects theories, concepts and data that can be done on variables in research. The findings empirically explain that the higher the face value of male CEO masculinity has an impact on reducing research & development costs, and vice versa the lower the face value of male CEO masculinity has an impact on increasing research & development. The practical implications of the research results can help the Indonesian Association of Accountants in developing Financial Accounting Standard No. 19 in Indonesia. The theoretical implications of the research results can explain the Theory of Agency and the Theory of Consistency of Behavior. The policy implications of the results of the study can provide empirical evidence that the higher the facial value of male CEO masculinity has an impact on reducing research & development, while also the lower the face value of male CEO masculinity has an impact on increasing research & development.

Abstract: The genus Acaryochloris is unique among phototrophic organisms due to the dominance of chlorophyll d in its photosynthetic reaction centres and light-harvesting proteins. This allows Acaryochloris to capture light energy for photosynthesis over an extended spectrum of up to ~760 nm in the near infra-red (NIR) spectrum. Acaryochloris sp. has been reported in a variety of ecological niches, ranging from polar to tropical shallow aquatic sites. Here, we report a new Acarychloris strain isolated from an NIR-enriched stratified microbial layer 4-6 mm under the surface of stromatolite mats located in the Hamelin Pool of Shark Bay, Western Australia. Pigment analysis, by traditional spectrometry/fluorometry, flow cytometry and spectral confocal microscopy identify unique patterns in pigment distribution that likely reflect niche adaption. For example, unlike the original A. marina species (type strain MBIC11017), this new strain, Acarychloris LARK001, shows little change in the chlorophyll d/a ratio in response to changes in light wavelength, displays a different Fv/Fm response and lacks detectable levels of phycocyanin. Indeed, 16S rRNA analysis supports the identity of the A. marina LARK001 strain as distinct from the A. marina HICR111A strain first isolated from Heron Island, previously found on the Great Barrier Reef, under coral rubble on the reef flat. Taken together, A. marina LARK001 is a new cyanobacterial strain adapted to the stromatolite matts in Shark Bay.

Background: Vitamin D was studied in regards to its possible impact on body mass reduction and metabolic changes in adults and children with obesity yet there were no studies assessing the impact of vitamin D supplementation during a weight management programme in children and adolescence. The aim of our study was to assess the influence of 26 weeks of vitamin D supplementation in overweight and obese children undergoing an integrated 12-months’ long weight loss programme on body mass reduction, body composition and bone mineral density. Methods: A double-blind randomized placebo-controlled trial. Vitamin D deficient patients ( <30 ng/ml level of vitamin D) aged 6-14, participating in multidisciplinary weight management programme were randomly allocated to receiving vitamin D (1200 IU) or placebo for the first 26 weeks of the intervention. Results: Out of the 152 qualified patients, 109 (72%) completed a full cycle of four visits scheduled in the programme. There were no difference in the level of BMI change. Although the reduction was greater in the vitamin D vs. placebo group (-4.28 ± 8.43 vs. -2.53 ±6.10) the difference was not statistically significant (p=0.319). Similarly the reduction in fat mass – assessed both using bioimpedance and DEXa was achieved, yet the differences between the groups were not statistically significant. Conclusions: Our study ads substantial results to support the thesis on no effect of vitamin D supplementation on body weight reduction in children and adolescents with vitamin D insufficiency undergoing a weight management programme. Trial registration no: NCT 02828228; trial registration date: 8 June 2016 registered in: ClinicalTrials.gov.

Organic light-emitting diodes (OLEDs) have garnered considerable attention in academic and industrial circles due to their potential applications in flat panel displays and solid-state lighting technologies, leveraging the advantages offered by organic electroactive derivatives over their inorganic counterparts. The thin and flexible design of OLEDs enables the development of innovative lighting solutions, facilitating the creation of customizable and contoured lighting panels. Among the diverse electroactive components employed in the molecular design of OLED materials, the benzophenone core has attracted much attention as fragment for synthesis of organic semiconductors. On the other hand, the benzophenone also functions as a classical phosphor with high intersystem crossing efficiency. This characteristic makes it as compelling candidate for effective reverse intersystem crossing, potentially leading to the development of thermally activated delayed fluorescent (TADF) emitters. These emitting materials witnessed a pronounced interest in recent years due to their incorporation in metal-free electroactive frameworks and the capability to convert triplet excitons into emissive singlet excitons through reverse intersystem crossing (RISC), consequently achieving exceptionally high external quantum efficiencies (EQEs). This review article comprehensively overviews the synthetic pathways, thermal characteristics, electrochemical behaviour and photo-physical properties of the derivatives based on benzophenone. Furthermore, we explore their applications in OLED devices, both as host materials and emitters, shedding light on the promising opportunities that benzophenone-based compounds present in advancing OLED technology.

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50nmol/L) should also ensure any benefits for multiple sclerosis.

Profiling technologies, such as proteomics, allow the simultaneous measurement and comparison of thousands of plant components without prior knowledge of their identity. The combination of these non-targeted methods facilitates a more comprehensive approach than targeted methods and thus provides additional opportunities to identify genotypic changes resulting from genetic modification, including new allergens or toxins. The purpose of this study was to investigate unintended changes in GM Bt maize grown in South Africa. In the present study, we used bi-dimensional gel electrophoresis based on fluorescence staining, coupled with mass spectrometry in order to compare the proteome of the field-grown transgenic hybrid (MON810) and its near-isogenic counterpart. Proteomic data showed that energy metabolism and redox homeostasis were unequally modulated in GM Bt and non-GM maize variety samples. In addition, a potential allergenic protein – pathogenesis related protein -1 has been identified in our sample set. These finding highlight the suitability of unbiased profiling approaches to complement current GMO risk assessment practices worldwide.

GbtXyl43A, a β-xylosidase that is isolated from Geobacillus thermoleovorans IT-08 and grouped in GH43 family. The substitution of 121Asp residue with Asn in GbtXyl43A caused decrease the enzyme activity. The aim of this study, determine the kinetic characteristics of wild-type GbtXyl43A and D121N variant using Vmax, KM, kcat, and kcat/KM. These parameters indicated catalytic mechanism of GbtXyl43A and its derivative. All of them were produced in Escherichia coli BL21 star. The purification of wild-type GbtXyl43A using affinity chromatography, but D121N variant also required anion-exchange chromatography. The specific activity of wild-type GbtXyl43A and D121N variant were 0.471 U mg-1 in purity level 55,44 and 0.012 U mg-1 in purity level 2,407, respectively. Both enzymes had same molecular weight, ~58 kDa. The kinetic parameters of wild-type GbtXyl43A were KM: 2.845 mM, kcat: 0.033 s-1, Vmax: 0.0033 mM min-1and kcat/KM: 0.0115 s-1mM-1. Furthermore, the KM, kcat, Vmax, and kcat/KM values of D121N variant were 4.565 mM, 1.01 × 10-4 mM min-1, 0.140 × 10-4 s-1, and 0.0307 s-1mM-1, respectively. The KM value of the D121N variant was higher than its wild type and showed the affinity of D121N variant was lower than GbtXyl43A

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

The appropriate concentration of vitamin D in the athlete’s body is essential for its proper functioning, especially in terms of muscular health, by enhancing recovery and oxygen consumption. Soccer players are required to perform frequent sprints and change of directions during training and competition. The aim of the present study was to establish whether the level of vitamin D (measured by 25-hydroxyvitamin D concentrations- 25(OH)D) in blood serum has any influence on speed (s) and change of direction (COD, s) performance. Material and methods: Twenty male soccer players from the top league in Poland participated in the study. All subjects' were evaluated for the serum concentration of 25(OH)D at the beginning of the preseason. . The linear sprint test was performed at 5m and 30m and COD (time and deficit), was evaluated at 30m at the beginning and after 6 weeks of preparatory period. Results: The results revealed that 50% of soccer players had an insufficient level or a deficit of 25(OH)D (≤ 30 ng/ml), with 20% having a significant deficiency of 30 ng/ml).There were no statistically significant correlations between the training effect for the variables ∆5m (before - after) and ∆30m (before - after). Statistically significant positive correlations were found between the training effect for the variables ∆COD (before - after) (R=0.62/p=0.003) and ∆deficit (before-after) (R=0.47/p=0.039). With a higher concentration of vitamin D in the blood, the training effect for COD and the deficit increased, which was visible in the faster performance of the COD test. No statistically significant differences were found for the mean values of the variables ∆5m (before - after) and ∆30m (before - after) in the group of subjects whose 25(OH)D concentration was 30mg /ml. Significant differences were noticed for the variables ∆COD (m=0.60 [s]) and ∆deficit (m=0.56[s]) in the group of subjects whose 25(OH)D concentration was 30mg /ml. The training effect was significantly higher for the group of subjects whose 25(OH)D concentration was above 30 mg/ml, which was observed by the faster performance of the COD test in this group of subjects. Conclusions: The serum concentration of vitamin D affects training adaptations of muscles. A lower concentration of Vitamin D seems to have a detrimental effect on the change of direction performance. Soccer players whose blood serum 25(OH)D concentrations were >30mg/ml achieved better results in the applied fitness tests.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n=148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Se-rum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤ 16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β= -0.018, 95% CI -0.033 to -0.003, P=0.022) and 0.048 SD (standardized β= -0.048, 95% CI -0.083 to -0.014, P=0.006), respectively. Additionally, the high serum 25OHD groups (> 95.9 nmol/L) had 0.038 SD (standardized β= -0.038, 95% CI -0.072 to -0.004, P=0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusion: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

Increased construction activities in Australia have led to the generation of a massive volume of construction and demolition (C&D) waste annually. Management of this volume of waste requires an effective waste framework. The literature reported that the current Australian waste framework does not meet expectations and needs immediate improvements. This study was therefore conducted to seek the key C&D stakeholders' opinion about various issues identified in this waste stream. The specific objectives of this study are identification of the main barriers to effective C&D waste management, the impact of current regulations and opportunities to enhance the current C&D waste management system. A survey was conducted in 2019 to capture the stakeholders' perception. 132 participants from various industries and government agencies based in various Australian jurisdictions took part in the survey. The key results showed that the main barriers towards an effective management system are "overregulation, tough acceptance criteria, and increased testing requirements", "lack of local market" and "culture, poor education and low acceptance". Furthermore, a low number of participants indicated that the current legislation encourages waste recovery activities. The main areas of improvements included "providing a guideline that determines the accepted level of contamination for reusing C&D waste”, "preparation of guidelines on requirements of using recycled C&D materials in different industries" and "setting target for reduction, reusing, and recycling C&D waste". The results can inform policy development and be used as evidence for a broader discussion to solve lasting issues in C&D waste management.

Obesity in children is associated with vitamin D (VD) deficiency and cardiometabolic abnormalities. To analyze the effects of VD supplementation in adolescents with obesity enrolled in a weight-loss program. Adolescents with obesity (n=26) and with normal weight (n=23; controls) were matched for age, sex, and puberty stage. The obesity group followed a 3-month weight-loss program that combined a reduced caloric intake with interval training physical activity and during which they received or not VD supplementation (4000 IU/d) (n=13/group; random assignation). The anthropometric parameters (BMI z-score, fat mass); serum levels of 25(OH)D, calcium and parathyroid hormone (PTH), cardiometabolic factors (triglycerides, HDL, and LDL cholesterol), fasting glucose and insulin, and homeostasis model assessment of insulin resistance index; diastolic, systolic and mean blood pressure, and inflammatory status (C-reactive protein, CRP) were measured at baseline and at the end of the 3-month program. At baseline, 25(OH)D concentration was lower and VD insufficiency (25(OH)D levels <50 nmol/L) rate was higher (73% vs 22%) in the obesity than in the normal-weight group. All cardiometabolic factors were altered in the obesity compared with the normal-weight group. After the 3-month weight-loss program, 25(OH)D levels was >50 nmol in all adolescents with obesity, but only in 46% of normal-weight adolescents. Moreover, the weight-loss program improved the cardiometabolic factors, inflammatory status (CRP) and physical performance, but VD supplementation did not have any additional effect. Analysis only of the adolescents with obesity and VD deficiency (25(OH)D <50 nmol/L) at baseline showed a significant correlation between the change in PTH and CRP (p=0.02) in the supplemented obesity group, while the increase in 25(OH)D only tended to be correlated with CRP decrease. Vitamin D supplementation could reduce VD insufficiency in adolescent with obesity, but does not have any additional effect on cardiometabolic factors when combined with a weight-loss program.

Antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPL). Preeclampsia (PE) complicates about 10-17% of pregnancies with APS. However, only early onset PE (< 34 weeks of gestation) belongs to the clinical criteria of APS. The similarities in the pathophysiology of early onset PE and APS emphasize an association of these two syndromes. Overall, both are the result of a defective trophoblast invasion and decidual transformation at early gestation. Women with APS are at increased risk for prematurity; the reasons are mostly iatrogenic due to placental dysfunction, such as PE or FGR. Interestingly, women with APS have also an increased risk for preterm delivery, even in the absence of FGR and PE and therefore not indicated but spontaneous. The basic treatment of APS in pregnancy is low-dose-aspirin and low-molecular- weight-heparin. Nevertheless, up to 20-30% of women develop complications at early and late gestation despite basic treatment. Several additional treatment options have been proposed, with Hydroxychloroquine (HCQ) being one of the most efficient. Additionally, nutritional interventions, such as intake of vitamin D have shown promising beneficial effects. Curcumin, due to its antioxidant and anti-inflammatory properties, might be considered as additional intervention as well.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

Thermal sterilization is generally avoided for 3-D printed components because of the relatively low deformation temperatures for common thermoplastics used for material extrusion-based additive manufacturing. 3-D printing materials required for high-temperature heat sterilizable components for COVID-19 and other applications demands 3-D printers with heated beds, hot ends that can reach higher temperatures than polytetrafluoroethylene (PTFE) hot ends and heated chambers to avoid part warping and delamination. There are several high temperature printers on the market, but their high costs make them inaccessible for full home-based distributed manufacturing required during pandemic lockdowns. To allow for all these requirements to be met for under $1,000, the Cerberus – an open source three-headed self-replicating rapid prototyper (RepRap) was designed and tested with the following capabilities: i) 200^oC-capable heated bed, ii) 500^oC-capabel hot end, iii) isolated heated chamber with 1kW space heater core and iv) mains voltage chamber and bed heating for rapid start. The Cereberus successfully prints polyetherketoneketone (PEKK) and polyetherimide (PEI, ULTEM) with tensile strengths of 77.5 and 80.5 MPa, respectively. As a case study, open source face masks were 3-D printed in PEKK and shown not to warp upon widely home-accessible oven-based sterilization.

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

Three different fields intersect in search of an understanding of the point-of-origin of modern-age diseases: 1) D-amino acids and their role under stress conditions; 2) evolutionary origin of the mitochondrion organelle in the eukaryotic cell; and 3) gut microbiota and human healthHere it is first suggested that D-amino acids function as universal signaling agents, after having evolved as prokaryotic communication, part of an organic communication process that governs the basic activities of all the cells and coordinates cell action.Mitochondria (symbiotic prokaryotic organelles), are creative source of D-amino acids as signaling agents in the central nervous system and in the neuroendocrine systems.Amino acids racemases catalyzes the conversion between the L-enantiomers ( protein building blocks) into D-enantiomers (signaling agents).It is suggested that hectic modern life may affect human health by causing stress to the gut microbiota. These affected, gut microbiota then secrete D-amino acids that enter the blood stream, as signaling agents, causing communication errors in the central nervous system, and in the neuroendocrine systems due to excessive quantity of D-amino acids.Treating gut microbiota with inhibitors of amino acids racemases or finding D-amino acid scavengers may be used in developing novel therapeutic strategies for diseases related to the central nervous system and neuroendocrine systems caused by stressed gut microbiota.

Phenotyping is the task of measuring plant attributes for analyzing the current state of the plant. In agriculture, phenotyping can be used to make decisions concerning the management of crops, such as the watering policy, or whether to spray for a certain pest. Currently, large scale phenotyping in fields is typically done using manual labor, which is a costly, low throughput process. Researchers often advocate the use of automated systems for phenotyping, relying on the use of sensors for making measurements. The recent rise of low cost, yet reasonably accurate, RGB-D sensors has opened the way for using these sensors in field phenotyping applications. In this paper, we investigate the applicability of 4 different RGB-D sensors for this task. We conduct an outdoor experiment, measuring plant attribute in various distances and light conditions. Our results show that modern RGB-D sensors, in particular, the Intel D435 sensor, provides a viable tool for close range phenotyping tasks in fields.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of RT-PCR and qRT-PCR found that the relative expression of PLD6 gene in the testicular tissues of 2-year-old Simmental calves was significantly higher than that of 6-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker VASA. Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piRNA binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and PIWIL2. In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.

We investigate entropy generation in unsteady three-dimensional axisymmetric MHD nanofluid flow over a non-linearly stretching sheet. The flow is subject to thermal radiation and a chemical reaction. The conservation equations were solved using the spectral quasi-linearization method. The novelty of the work is in the study of entropy generation in three-dimensional axisymmetric MHD nanofluid and the choice of the spectral quasilinearization method as the solution method. The effects of Brownian motion and thermophoresis are also taken into account when the nanofluid particle volume fraction on the boundary in passively controlled. The results show that as the Hartman number increases, both the Nusselt number and the Sherwood number decrease whereas the skin friction increases. It is further shown that an increase in the thermal radiation parameter corresponds to a decrease in the Nusselt number. Moreover, entropy generation increases with the physical parameters.

Pyracantha angustifolia has been used in traditional medicine to treat a range of diseases of the stomach and improve digestion, blood circulation, diarrhea, dysentery, and hemostasis. This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from P. angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, as well as ABTS and DPPH radical scavenging activities, and have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid beta-d-glucosylester (HG), and cimidahurinine (CD) had strong inhibitory effects of melanin production, TYR activity, and ABTS and DPPH radical scavenging activities. Western blot analysis showed that HG and CD suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.

Aging is the results of several complex and multifactorial processes, where several agents contribute to increase intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms, finely regulated and strictly interconnected, initiating or contributing to biological changes anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic affects. Vitamin D (VitD) is known to have positive impact not only on muscle and bone health, but also on several extra-skeletal districts, due to the widespread presence of VDRs (VDR). VitD and VDR could be molecules potentially targeting the hallmark of aging network. To date, evidence about the potential effect of VitD on the hallmark of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seems to confirm the modulatory effect of VitD on some hallmarks aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Cathode materials based on SrCoO3- perovskite-type oxides hold great potential, given the huge oxygen permeability exhibited by the cubic phase of this oxide, which must be stabilized though suitable cationic substitutions. We present here two novel materials of the series Sr1-xYxCoO3- (x= 0.1, 0.2), prepared by solid state reactions. The crystalline structure was explored by neutron powder diffraction. At RT, we identified a subtle tetragonal superstructure, yet preserving the wanted framework of vertex-sharing CoO6 octahedra. A noteworthy result of the neutron analysis is the presence of conspicuous amounts of oxygen vacancies, ordered in layers and responsible for the formation of the mentioned superstructure. The stability was investigated by thermal analysis, using thermogravimetry (TGA). The electrical conductivity gave a maximum value of 800 °C of 122 S·cm–1. To determine the resistance associated with the oxygen reduction reaction (ORR), electrochemical impedance spectroscopy as a function of temperature was carried out, finding a value for the activation energy of Ea= 0.82 eV. This is a much lower value than that usually obtained for cathodes with a high catalytic activity for the oxygen reduction reaction. In single-cell tests, the materials generated a power density up to 0.25 Wcm−2 at 800ºC, using pure H2 as fuel. All these features make this perovskite a suitable candidate as cathode material in intermediate-temperature SOFCs

Bioinformatics analysis of the sequences of orthologous zinc-containing peptidases of the M15_C subfamily revealed the presence of a conserved tryptophan residue near the active site, which is not involved in the formation of the protein core. Site-directed mutagenesis of this Trp114/109 residue using two representatives of the family, L-alanoyl-D-glutamate peptidases of bacteriophages T5 (Calcium-activated EndoT5) and RB49 (EndoRB49, without ion regulation) as an example, and further analysis of the 1H NMR spectra of the mutants showed that a decrease in the volume of the W → F → A residue leads to changes in the hydrophobic core and active center of the protein, and also decreased affinity for regulatory Ca2+ in the EndoT5 mutants. The inactive T5W114A mutant lacks the ability to bind the substrate. In general, the conserved Trp114/109 residue, due to the spatial restrictions of its side chain, significantly affects the formation of the catalytically active form of the enzyme and is critical for catalysis.

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

Relapses and resistance to therapeutic agents are major barriers for treatment of acute myeloid leukemia (AML) patients. This unfavorable circumstance emphasizes the need for new strategies targeting drug-resistant cells. As IDH mutation is present in the preleukemic stem cells and systematically conserved at relapse, targeting mutant IDH cells would be essential to achieve a long-term remission in the AML subgroup with IDH mutation. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutation, we showed that the presence of IDH mutation through the production of an oncometabolite (R)-2-HG induces vitamin D receptor related transcriptional programs, priming these AML cells to differentiate with pharmacological doses of ATRA or/and VD. This activation occurs in a CEBP-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutation and vitamin D pathway to differentiate in AML, revealing a novel therapeutic approach easily transferable/immediately applicable in clinics for this subgroup of AML patients.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

Background Bangladesh has been attracting international students on various subjects in recent times. Every year students from different parts of the world come to study undergraduate and postgraduate courses, mostly at private universities in Bangladesh. This study evaluates the depression status among international students who are studying dentistry in Bangladesh. Methods This cross-sectional survey was conducted among International undergraduate dental students who enrolled in the Bachelor of Dental Surgery program in nine public and private dental colleges in Bangladesh. A total of 206 students completed the survey, and CES-D 10 items Likert scale questionnaire was used for data collection. The Cronbach alpha for CES-D 10 scale items for this population is 0.812. Results The majority of the students (79.5%) are below 24 years of age, and students who cannot communicate well in Bengali (Bangla), about 60% of them have experienced depression. About 77.3% (p< 0.00) of the international students having financial difficulties exhibited depression. The international students who went through financial problems were two times more likely to suffer from depression (OR=2.38; p-value <0.01). Conclusion This study tried to highlight the struggles faced by international students in Bangladesh studying dentistry. It is evident from the findings that several factors influence students' mental well-being during demanding dental education years.

Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.

The impact of nutrition on immunity is an intense area of research. Malnutrition is linked to a higher risk of microbial infections, while severe infections usually lead to a nutritional imbalance in affected patients. The nutritional status has an impact on the severity of the ongoing SARS-CoV-2 infection. Studies conducted on small numbers of patients have shown the benefits of maintaining optimal vitamin (B12 and D) and mineral (zinc and magnesium) balance in reducing the intensity of COVID-19. Although consuming a balanced diet with a healthy lifestyle is always desirable, the importance of such practice is even more meaningful during the COVID-19 pandemic. Keeping an optimal balance of vitamins and minerals through healthy dietary habits helps to maintain a robust immune system that is essential to combat invading microbial pathogens, including SARS-CoV-2.

Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

The study evaluated the impact of supplementing ZH in combination with D3 on growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper x Katahdin cross lambs (37.3±5.72 kg) were utilized in a 29 d experiment in a complete randomized block design with a 2x2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg /kg PV-1) and two levels of D3 for 7 d (0 and 1.5x106 IU/d-1). ZH improved (P≤0.05) average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p≤0.03). However, ZH increased (p<0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (P≤0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus muscle (LM) by 1.7% (p=0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve meat tenderness produced by ZH supplementation.

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

Given the high number of vehicle-crash victims, it has been established as a priority to reduce this figure in the transportation sector. For this reason, many of the recent researches are focused on including control systems in existing vehicles, to improve their stability, comfort and handling. These systems need to know in every moment the behavior of the vehicle (state variables), among others, when the different maneuvers are performed, to actuate by means of the systems in the vehicle (brakes, steering, suspension) and, in this way, to achieve a good behavior. The main problem arises from the lack of ability to directly capture several required dynamic vehicle variables, such as roll angle, from low-cost sensors. Previous studies demonstrate that low-cost sensors can provide data in real-time with the required precision and reliability. Even more, other research works indicate that neural networks are efficient mechanisms to estimate roll angle. Nevertheless, it is necessary to assess that the fusion of data coming from low-cost devices and estimations provided by neural networks can fulfill the reliability and appropriateness requirements for using these technologies to improve overall safety in production vehicles. Because of the increasing of computing power, the reduction of consumption and electric devices size, along with the high variety of communication technologies and networking protocols using Internet have yield to Internet of Things (IoT) development. In order to address this issue, this study has two main goals: 1) Determine the appropriateness and performance of neural networks embedded in low-cost sensors kits to estimate roll angle required to evaluate rollover risk situations. 2) Compare the low-cost control unit devices (Intel Edison and Raspberry Pi 3 Model B), to provide the roll angle estimation with this artificial neural network-based approach. To fulfil these objectives an experimental environment has been set up composed of a van with two set of low-cost kits, one including a Raspberry Pi 3 Model B, low cost Inertial Measurement Unit (BNO055 - 37€) and GPS (Mtk3339 - 53€) and the other having an Intel Edison System on Chip linked to a SparkFun 9 Degrees of Freedom module. This experimental environment will be tested in different maneuvers for comparison purposes. Neural networks embedded in low-cost sensor kits provide roll angle estimations very approximated to real values. Even more, Intel Edison and Raspberry Pi 3 Model B have enough computing capabilities to successfully run roll angle estimation based on neural networks to determine rollover risks situation fulfilling real-time operation restrictions stated for this problem.

Reliable quantification of pulmonary arterial pressure is essential in the diagnostic and prognostic assessment of a range of cardiovascular pathologies including rheumatic heart disease, yet an accurate and routinely available method for its quantification remains elusive. This work proposes an approach to infer pulmonary arterial pressure based on scientific machine learning techniques and non-invasive, clinically available measurements. A 0-D multicompartment model of the cardiovascular system was optimized using several optimization algorithms, subject to forward-mode automatic differentiation. Measurement data were synthesized from known parameters to represent the healthy, mitral regurgitant, aortic stenosed and combined valvular disease situations with and without pulmonary hypertension. Eleven model parameters were selected for optimization based on 95 % explained variation in mean pulmonary arterial pressure. A hybrid Adam and limited-memory Broyden-Fletcher-Goldfarb-Shanno optimizer yielded the best results with input data including valvular flow rates, heart chamber volume changes and systematic arterial pressure. Mean absolute percentage errors ranged from 1.8 % to 3.78 % over the simulated test cases. The model was able to capture pressure dynamics under hypertensive conditions with pulmonary arterial systole, diastole, and mean pressure average percentage errors of 1.12 %, 2.49 % and 2.14 %, respectively. The relatively low errors highlight the potential of the proposed model to recover pulmonary pressures for diseased heart valve and pulmonary hypertensive conditions.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

The cause of sarcoidosis is unknown, and vitamin D is contraindicated to treat the condition. We therefore ask what causes sarcoidosis and why vitamin D can be dangerous for those so afflicted. We propose a contrary hypothesis: sarcoidosis is a physiological process of defense against cancer that requires the substrate vitamin D. We tested this hypothesis, finding many case reports involving sarcoidosis and cancer—further cases of cancer mimicry by sarcoidosis. Several reports describe spontaneous healing of cancer in the presence of sarcoidosis. In the context of the granulomas of sarcoidosis, monocytes are the site of vitamin D release. Furthermore, active vitamin D can control cancer cells by using the vitamin D receptors of the nucleus. That granulomas consistently do not caseate is explained as a confrontation with human molecules and the cancer cells’ complete absorption. The striking fact that granulomas of sarcoidosis mostly lack cancerous cells is interpreted as a result of a well-functioning sarcoidosis process. We view the typical sarcoidosis monocytic synthesis of active vitamin D as a successful defense against cancer: a theory we call the “endogenous program organizing cancer apoptosis” (EPOCA).

This study aims to test empirical research on the effect of financial resource ability, research and development (R &amp; D) on innovation orientation and competitive position. This study also examines the critical mediating role of innovation orientation and competitive position to achieving new products performance (NPP). This study used a quantitative research approach by comparing data from service industry and manufacture industry in Indonesia included in Indonesian-State-Ownership companies. The analysis unit in this study used middle managers and top managers who responsible for managing divisions within the Indonesian-State-Ownership companies. The number of respondents studied in this study was 287 sample. The purposive sampling technique was used in taking the research sample. This study indicated that financial resources abilities, research and development (R &amp; D) abilities positive effect on innovation orientation and competitive position. This study also testing the importance role of innovation orientation and a competitive position to enhancing new products performance (NPP).

Arginine shows Jekyll and Hyde behavior in several respects. It participates in protein folding via ionic and H-bonds and cation-pi interactions; the charge and hydrophobicity of its side chain makes it a disorder-promoting amino acid. Its methylation in histones; RNA binding proteins; chaperones regulates several cellular processes. The arginine-centric modifications are important in oncogenesis and as biomarkers in several cardiovascular diseases. The cross-links involving arginine in collagen and cornea are involved in pathogenesis of tissues but have also been useful in tissue engineering and wound-dressing materials. Arginine is a part of active site of several enzymes such as GTPases, peroxidases, and sulfotransferases. Its metabolic importance is obvious as it is involved in production of urea, NO, ornithine and citrulline. It can form unusual functional structures such as molecular tweezers in vitro and sprockets which engage DNA chains as part of histones in vivo. It has been used in design of cell-penetrating peptides as drugs. Arginine has been used as an excipient in both solid and injectable drug formulations; its role in suppressing opalescence due to liquid-liquid phase separation is particularly very promising. It has been known as a suppressor of protein aggregation during protein refolding. It has proved its usefulness in protein bioseparation processes like ion-exchange, hydrophobic and affinity chromatographies. Arginine is an amino acid, whose importance in biological sciences and biotechnology continues to grow in diverse ways.

Wear simulation aims to assess wear rates and their dependence on factors like load, kinematics, temperature, and implant orientation. Despite its significance, there's a notable gap in research concerning advancements in simulator control systems and the testing of clinically relevant waveforms. This study addresses this gap by focusing on enhancing the conventional proportional-integral-derivative (PID) controller used in joint simulators through the development of a fuzzy logic-based controller. Leveraging a single-input-multiple-output (SIMO) fuzzy logic control system, the study aimed to improve displacement control, augmenting the traditional Proportional-Integral (PI) tuning approach. Implementation and evaluation of a novel Fuzzy-PI control algorithm were conducted on the Leeds spine wear simulator. The study also included testing of daily-living (DL) profiles, particularly from the hip joint, to broaden the scope of simulation scenarios. While both the conventional PI controller and the Fuzzy-PI controller met ISO tolerance criteria for the spine flexion-extension (FE) profile at 1Hz, the Fuzzy-PI controller demonstrated superior performance at higher frequencies and with DL profiles due to its real-time adaptive tuning capability. The Fuzzy-PI controller represents a significant advancement in joint wear simulation, offering improved control functionalities and a more accurate emulation of real-world physiological dynamics.

This manuscript presented an autonomous home farm for predicting metrological characteristics that can not only automate the process of growing crops but also, due to a neural network, significantly increase the productivity of the farm. The developed farm monitors and manages the following indicators: illumination, soil PH, air temperature, earth temperature, air humidity, CO2 concentration, and soil moisture. The presented farm can also be considered as a device for testing various weather conditions to determine the optimal temperature characteristics for different crops. This farm as a result is completely autonomous grows tomatoes at home.

This study aims to analyse whether Chinese companies' R&amp;D investment affects management innovation performance. Also, this dissertation defines management innovation as diversification strategies such as technology and industry diversification and analyzes the impact of these diversification strategies. In particular, this paper analyzes whether R&amp;D investment leads to technology and industry diversification and whether technology diversification creates a mediating effect in the process of R&amp;D investment leading to industry diversification. The analysis results can be summarized as follows: First, R&amp;D investment showed a significant positive relationship with industry diversification. Second, R&amp;D investment shows a significantly positive relationship with technology diversification. Third, technology and industry diversification showed a positive relationship. Fourth, this study examined the mediating role of technology diversification, and it was confirmed that technology diversification plays a mediating role in the effect of R&amp;D investment on industry diversification. R&amp;D investment and business innovation play a key role in the sustainable development of enterprises, and the findings of this paper have important reference value for enterprises' R&amp;D investment decision-making. The results of this study provide the following implications that Chinese companies improve business innovation performance by increasing their R&amp;D investment, promoting innovative R&amp;D, and improving technology diversification and industry diversification strategies.

Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are endemic threats to cassava production. To fill the existing gaps in the understanding of the epidemiology of these diseases in Côte d’Ivoire, nationwide field surveys were conducted in 2016, 2017 and 2020. The leaf samples collected were analysed by PCR. CBSD was not detected in all fields visited. However, an increase of CMD incidence was observed from 45.95% in 2016 to 51.37% in 2020 while CMD severity remained moderate over the years with a mean value of 2.29. Low whiteflies number was observed in field and decreasing over the years. Molecular analysis allowed detection of East African cassava mosaic Cameroon virus (EACMCMV) in single as well as in mixed infection with African cassava mosaic virus (ACMV). Single EACMCMV infection, which was detected only in three agroecological zones of the eastern Côte d’Ivoire in 2016, spread throughout the country in 2017 and became more widespread in 2020 with a preponderance in the central and southern zones, whereas the ACMV+EACMCMV coinfection has spread to the entire zones studied. Knowing the dynamics of the evolution of these viruses across the country, better disease management strategies could be adopted to control the disease.

Limited studies have shown that exposure to arsenic is associated with serum vitamin D levels, but the results are still inconsistent. A cross-sectional study of 762 participants was conducted in Wenshui Country, Shanxi Province, which was identified as an area of water-borne arsenicosis. The results showed positive relationship between arsenic species (iAs, MMA, DMA) and serum 25(OH)D. Binary logistic regression analysis showed that the significant increases of 0.4% and 0.6% in the risk of vitamin D excess for every 1-unit increment in the Box-Cox transformed urinary tAs and DMA, respectively. After stratifying populations based on arsenic methylation metabolic capacity, each one-unit increase in the Box-Cox transformed tAs level was associated with increases of 0.064 (95%CI: 0.032 to 0.096) in serum 25(OH)D in the populations with iAs% above the median. In the populations with skin hyperkeratosis, urinary iAs was positively associated with serum 25(OH)D (β=0.592, 95%CI: 0.041 to 1.143). Overall, our findings support the positive relationship between urinary arsenic and serum 25(OH)D.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

Ketamine is a dissociative anesthetic and antidepressant with several biological targets. Among the many targets, ketamine, notably, has an antagonistic effect on molecular N-methyl-D-aspartate (NMDA) receptors and has been identified as a non-competitive inhibitor of these receptors. Although ketamine has a wide range of therapeutic uses in the clinical setting, it is often used recreationally due to its psychoactive and analgesic effects. Regardless of the indication, prenatal exposure to ketamine has been widely investigated. The misuse of this drug, particularly in pregnant women, has been a point of concern. The neurotoxic potential of ketamine positions it as a danger to a developing fetus. Furthermore, the ability of ketamine to cross the blood-placental barrier poses a threat to the health and maturation processes of the neonate. This paper reviewed published work that explores the mechanisms through which prenatal ketamine exposure can cause altered neurodevelopment, neurobehavior, and the physiological consequences that follow. By exploring investigations using multiple different subjects such as: rodents, non-human primates, and human subjects, this paper develops a full picture of the existing data to generate a strong foundation for improved and informed public health policies.

Water reuse for irrigation is increasingly recognized as an essential and economical strategy in areas with water scarcity. A simple, low-cost, low-maintenance, and highly efficient Pond-In-Pond (PIP) treatment system can be used for wastewater reuse. PIP is a treatment technology in which two types of ponds -- anaerobic and aerobic -- are combined into a single pond and consist of a deeper inner section entirely submerged within the outer pond. Previous studies on PIPs and PIP-like systems have reinforced the potential for reuse through promising performance results with BOD removal over 80% and a reduction in land area requirements by approximately 40%. Yet, no prior efforts have been made to understand the performance mechanism of such systems. This study makes use of two, 2-D modeling tools in developing a fundamental understanding of PIP flow dynamics and the expected performance. The modeling results showed that the PIP configuration offers improved flow diversion along with reduced flow velocity. Additionally, the PIP retained approximately 17% more (p<0.05) particles than the traditional pond with most of the particles concentrated within the inner pond. Lower velocity and the higher solids retention in the PIP thus allowed for better treatment performance compared to traditional ponds. The findings from this study can be used as preliminary data for future in-depth investigations of the PIP system leading toward effective and optimal designs. This will help address the major societal concern of water scarcity with low-cost and effective wastewater treatment.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults, and evaluated the effect of a digital lifestyle program on the nutritional status and nutrition health behaviors of these individuals. A micronutrient panel was measured in 348 participants, alongside a dietary assessment. One-hundred users subsequently underwent a remeasurement. We identified at least one nutritional imbalance in 301 individuals (86.5%). 80% improved and normalized B6, 67% improved folate, 70% improved B12, and 86% improved vitamin D. Iron abnormalities were corrected in 75% of participants. In conclusion, this study found micronutrient deficiencies of easily obtainable vitamins through diet or supplementation such as B vitamins and vitamin D were more prevalent than expected in a Dutch population. This can partly be explained by an insufficient consumption of food groups rich in B vita-mins. Our preliminary results in those remeasured after a digitally-enabled lifestyle intervention show these imbalances can be corrected with adequate behavioral support in a “food as medicine” approach complemented with supplementation where needed.

Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.

In this paper, we first define the concepts of r-fuzzy soft α-open (semi-open and δ-open) sets on fuzzy soft topological spaces based on the article Aygunoglu et al. (Hacet. J. Math. Stat., 43 (2014), 193-208), and the relations of these sets with each other are established. In addition, we introduce the concepts of fuzzy soft δ-closure (δ-interior) operators, and study some properties of them. Also, the concept of r-fuzzy soft δ-connected sets is introduced and studied with help of fuzzy soft δ-closure operators. Thereafter, we define the concepts of fuzzy soft α-continuous (β-continuous, semi-continuous, pre-continuous and δ-continuous) functions, which are weaker forms of fuzzy soft continuity, and some properties of these functions along with their mutual relationships are discussed. Moreover, a decomposition of fuzzy soft α-continuity and a decomposition of fuzzy soft semi-continuity is obtained. Finally, as a weaker form of a fuzzy soft continuity, the concepts of fuzzy soft almost (weakly) continuous functions are defined, and some properties are specified. Additionally, we explore the notion of continuity in a very general setting called, fuzzy soft (L, M, N, O)-continuous functions and a historical justification is introduced.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption; disruptions in this complex can affect bone metabolism. Methods: This study analyzed the changes in RANKL, OPG and 25(OH)D levels, the RANKL/OPG ratio, and other bone turnover markers (BTM) from diagnosis to complete remission in children with acute lym-phoblastic leukemia (ALL). This is a prospective observational cohort study. This study was carried out in the Instituto Mexicano del Seguro Social in Mexico City. Thirty-three patients (4-17 years) with newly diagnosed B-cell ALL were included. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A pe-ripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p=0.001) and osteocalcin (p

This article shows that the recently proposed latent D-scoring model of Dimitrov is statistically equivalent to the two-parameter logistic item response model. An analytical derivation and a numerical illustration are employed for demonstrating this finding. Hence, estimation techniques for the two-parameter logistic model can be used for estimating the latent D-scoring model. In an empirical example using PISA data, differences of country ranks are investigated when using different metrics for the latent trait. In the example, the choice of the latent trait metric matters for the ranking of countries. Finally, it is argued that an item response model with bounded latent trait values like the latent D-scoring model might have advantages for reporting results in terms of interpretation.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Several observational studies have indicated the potential associations between calcium, vitamin D(Vit-D) and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subjected to residual confounding factors and reverse causation. Therefore, we aim to explore the bidirectional causal effects between serum calcium, Vit-D, PTH and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratio (OR) with their 95% confidence intervals (CIs). The results of the inverse-variance-weighted method did not re-veal any causal relationship shared between genetically predisposed calcium (OR = 0.92, 95% CI: 0.80-1.06, P = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83-1.19, P = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a de-creased level of PTH (beta: -0.19, 95%CI: -0.34 to -0.04, P = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms by which IBS affects serum PTH need to be further investigated.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

Phospholipase Dα1 (PLDα1) belongs to phospholipases, a large phospholipid hydrolyzing protein family. PLDα1 has a substrate preference for phosphatidylcholine leading to enzymatic production of phosphatidic acid, a lipid second messenger with multiple cellular functions. PLDα1 itself is implicated in biotic and abiotic stress responses. We present here a shot-gun differential proteomic analysis on roots of two pldα1 mutants compared to the Col-0 wild type. Our data suggest new roles of PLDα1 in endomembrane transport, mitochondrial protein import and protein quality control and glucosinolate biosynthesis. Thus, we identified proteins involved in endocytosis, endoplasmic reticulum-Golgi transport and attachment sites of endoplasmic reticulum and plasma membrane (V-type proton ATPases, protein transport protein SEC13 homolog A, vesicle-associated protein 1-2, vacuolar protein sorting-associated protein 29, syntaxin-32, all upregulated in the mutants), mitochondrial import and electron transport chain (mitochondrial import inner membrane translocase subunits TIM23-2 and TIM13, mitochondrial NADH dehydrogenases, ATP synthases, cytochrome c oxidase subunit 6b-1, ADP,ATP carrier protein 2, downregulated in the mutants) and glucosinolate biosynthesis (3-isopropylmalate dehydrogenases 1, 2 and 3, methylthioalkylmalate synthase 1, cytochrome P450 83B1, Glutathione S-transferase F9, indole glucosinolate O-methyltransferase 1, adenylyl-sulfate kinase 1, all upregulated in mutants). Our results suggest broader biological roles of PLDα1 as anticipated so far.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy is scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy defibrillator (CRT-D) is preferred in patients that meet the established criteria. The need for cardiac pacing is 3-fold higher in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

Background: BNT162b2 represents the authorized mRNA vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS–CoV–2) causing Covid–19. Methods: We conducted a prospective, single–center observational study with 273 employees of a medical facility to determine the efficacy and safety of the BNT162b2 third dose in relation to sex and BMI, and explore the possible determinants of neutralizing IgG and 25–hydroxy (25–OH) vitamin D levels. Results: At the median follow–up of 4.7 months, 38 of the participants had Covid–19 following vaccination. The incidence of adverse events (AEs) was significantly higher in females vs. males (p < 0.0108) and subjects with a high BMI of ≥ 30 kg/m2 vs. low BMI (p < 0.0117). The values of IgG were significantly enhanced in males vs. females (p < 0.0004), participants with high BMI vs. low BMI (p < 0.0003), a high number of ≥3 AEs vs. low number of AEs (p < 0.0003), and following infection with Covid–19 vs. without Covid–19 (p < 0.0005). Multivariate analysis (MVA) showed sex, BMI, number of AEs, and Covid-19 to be of predictive significance. On the contrary, 25–OH vitamin D concentrations in individuals with high vs. low BMI were significantly reduced (p < 0.0144) but this was not evident in MVA. Conclusions: This study confirmed the high efficacy of BNT162b2 in real–world scenario and revealed that its safety was affected by sex and BMI. Higher IgG levels suggesting better protection against infection were present in males, participants with high BMI, a high frequency of AEs, and those who overcame Covid-19 following vaccination.

COVID-19 is a pandemic triggered by the coronavirus SARS-CoV-2 whose peak occurred in the years 2020 and 2021. The main target of the virus is the lung and infection is associated to an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 mice and then the evaluation of vitamin D (VitD) ability to control this process. The assays used to estimate the severity of lung involvement included total and differential number of cells in the BALF, histopathological analysis, quantification of T cell subsets and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates and flow cytometric analysis of cells recovered from lung parenchyma. IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in COVID-19 patients. This inflammatory process was significantly decreased by IN delivery of vitD, but not by its IP administration, suggesting that this hormone has therapeutic potential in COVID-19 if locally applied.

Background: Vitamin D and calcium are important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and other vitamins (A, C and K) are also involved. Vitamin D and other minerals, in fact, play an important role in calcium homeostasis and calcium absorption. Hip fractures incidence is higher in western countries, where calcium is frequently included in human diet, while the occurrence of these fractures is lower in developing countries, where diets are often poor in calcium. This situation is known as the “calcium paradox”, and may be partially explained considering phosphate toxicity, that can induce a disorder of mineral metabolism. It is important to maintain adequate dietary calcium-phosphate balance in order to perform a healthy life, reducing the risk of osteoporotic fracture in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the vitamin D precursor naturally found in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is originated by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as a provitamin D3. Dietary intake of vitamin D3 is very important when skin is exposed for short times to ultraviolet B light (UV-B) one of the three kinds of invisible light rays together with UV-A and UV-C. This can be considered the usual situation in northern latitudes and in winter season, or the typical condition for older people and/or for people with very white delicate skin. Actually, the recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teen-agers and adults, including women during pregnancy and lactation, to 15 μg for people over 65 years.

This work focuses on expressing the TSP with Time Windows (TSPTW for short) as a quadratic unconstrained binary optimization (QUBO) problem. The time windows impose time constraints that a feasible solution must satisfy. These take the form of inequality constraints, which are known to be particularly difficult to articulate within the QUBO framework. This is, we believe, the first time this major obstacle is overcome and the TSPTW is cast in the QUBO formulation. We have every reason to anticipate that this development will lead to the actual execution of small scale TSPTW instances on the D-Wave platform.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.