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.

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.

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.

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.

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.

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.

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.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

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.

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.

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.

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.

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

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.

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.

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.

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.

We obtain two generalizations of a known theorem of A. Alam and M. Imdad (Fixed Point Theory Appl. 17 (2015) 693–702) showing that some standard proofs can be obtained involving only Cauchy sequences of the successive approximations instead of the usual successive approximations sequences. Suitable examples prove the effective generalization of our results in metric spaces not necessarily complete.

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

Kinect is a device that has been widely used in many areas since it was released in 2010. Kinect SDK was announced in 2011 and used in many other areas than its original purpose, which was a controller for gaming. In particular, it has been used by a number of artists in digital media art since it is inexpensive and has a fast recognition rate. However, there is a problem. Kinect create 3D coordinates with a single 2D RGB image for x, y value - single depth image for z value. And this creates a significant limitation on the installation for interactivity of media art. Because the Cartesian XY coordinate and the spherical Z coordinate system are used in combination, depth error depending on the distance is generated, which makes real-time rotation recognition and coordinate correction difficult above coordinate system. This paper proposes a real-time calibration method of Kinect recognition range expansion for useful application in the digital media art area. The proposed method can recognize the viewer accurately by calibrating a coordinate in any direction in front of the viewer. 3,400 datasets witch acquire from experiment were measured as five stances: the 1m attention stance, 1m hands-up stance, 2m attention stance, 2m hands-up stance, and 2m hands-half-up stance, which were taken and recorded every 0.5 sec. The experimental results showed that the accuracy rate was improved about 11.5% compared with front measurement data according to Kinect reference installation method.

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.

The rapidly evolving field of artificial intelligence (AI) continues to witness the introduction of innovative open-source pre-trained models, fostering advancements in various applications. One such model is Llama 2, an open-source pre-trained model released by Meta, which has garnered significant attention among early adopters. In addition to exploring the foundational elements of the Llama v2 model, this paper investigates how these early adopters leverage the capabilities of Llama 2 in their AI projects. Through a qualitative study, we delve into the perspectives, experiences, and strategies employed by early adopters to leverage Llama 2's capabilities. For the purpose of data analysis, the capabilities inherent in the Llama 2 model were employed to conduct keyword extraction from the context of the early adopters' case studies. The findings shed light on the model's strengths, weaknesses, and areas of improvement, offering valuable insights for the AI community and Meta to enhance future model iterations. Additionally, we discuss the implications of Llama 2's adoption on the broader open-source AI landscape, addressing challenges and opportunities for developers and researchers in the pursuit of cutting-edge AI solutions. The present study constitutes an early exploration of the Llama 2 pre-trained model, holding promise as a foundational basis for forthcoming research investigations.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

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.

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.

Côte d’Ivoire has substantially neglected crop residues from farms in rural areas. This study aims to provide strategies for the sustainable conversion of crop residues to hydrogen. Using existing data and theoretical approaches, up to 16,801,306 tons of crop residues of 11 crop types were available in Côte d’Ivoire in 2019. A theoretical hydrogen potential of 1,296,424.84 tons was estimated from the crop residues. Technically, 907,497.39 tons of hydrogen is expected annually. Three scenarios of hydrogen project implementation developed indicated that the Ivorian industries can be supplied with 9,026,635 gigajoules of heat. Moreover, 17,910 cars and 4,732 buses can be supported in the transport sector. It is estimated that 817,293.95 tons of green ammonia for farmers can be supplied. Five million, seven hundred twenty-seven thousand, nine hundred ninety-two (5,727,992) households are expected to have access to 1,718.40 gigawatts of electricity. Due to these changes in transport, energy, industry, and agricultural sectors, a reduction of 1,644,722.08 tons of carbon dioxide per year can be achieved theoretically. With the scenarios, some 263,276.87 tons of hydrogen are exportable to other countries. Conversion of crop residues to hydrogen is a promising opportunity with environmental and socio-economic impact. Therefore, this study requires further extensive research.

Vitamin D is crucial for athletes' health and performance. Although the exact vitamin D requirements for athletes have not been established, maintaining 25(OH)D levels of at least 40 ng/ml is considered beneficial. This study aimed to determine whether an individual loading dose formula for vitamin D supplementation is suitable to meet a target value of 40 ng/ml and is more effective than standardized supplementation. In a 10-week supplementation study during the winter months in Germany, 90 athletes with insufficient vitamin D levels (25(OH)D<30ng/ml) were randomly assigned to receive either a universal dose of 2000 IU/day of vitamin D or a loading dose of 4000 IU/day, followed by a maintenance dose of 1000 IU/day. Total 25(OH)D concentration was measured from dried blood spots at three time points: at baseline, at the computed date of 40ng/ml, and after the 10-week period. Additionally, a vitamin D-specific questionnaire was issued. On the day when 25(OH)D blood concentrations of 40 ng/ml were calculated to prevail, the individualized group had a significantly higher 25(OH)D level than the standardized group (41.1+-10.9 ng/ml vs. 32.5+-6.4 ng/ml, p<0.001). This study demonstrated that the examined formula is suitable for athletes to achieve a 25(OH)D concentration of 40 ng/ml. This indicates that a personalized approach is more effective than a one-size-fits-all approach in restoring adequate vitamin D levels in athletes.

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.

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding 8 patients with pre-ESD levels of D-dimer >1.5 μg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but because the sedative effect of midazolam shows marked inter-individual variability, a “corrected midazolam dose” was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in subgroup analysis of the 103 patients who received midazolam. In subgroup analysis using the corrected midazolam dose as an explanatory variable, only corrected midazolam dose correlated with a change in D-dimer ≥ 1.0 μg/mL in multivariate analysis (odds ratio [OR]=1.5, 95% confidence interval [CI] 0.43–0.95; P=0.030). Corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT.

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.

Missing observation is a common problem in scientific and industrial experiments, particularly in a small-scale experiment. They often present significant challenges when experiment repetition is infeasible. In this research, we propose a multi-objective genetic algorithm as a practical alternative for generating optimal mixture designs that remain robust in the face of missing observation. Our algorithm prioritizes designs that exhibit superior D-efficiency while maintaining a high minimum D-efficiency due to missing observation. The focus on D-efficiency stems from its ability to minimize the impact of missing observations on parameter estimates, ensure reliability across the experimental space, and maximize the utility of available data. We study problems with three mixture components where the experimental region is an irregularly shaped polyhedral within the simplex. Our designs have proven to be D-optimal designs, demonstrating exceptional performance in terms of D-efficiency and robustness against missing observations. We provide a well-distributed set of optimal designs derived from the Pareto front, enabling experimenters to select the most suitable design based on their priorities using the desirability function.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

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 leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

The use of vitamin D (VitD) supplements has become widespread in the last decade due not only to the dissociation between the blood levels recommended as "optimal" and those shown by the healthy population, but also to its presumed beneficial effects on multiple disorders. This work evaluated the levels of 25-hydroxyvitamin D [25(OH)D] in a healthy population of European origin living in a region with high solar irradiation. In serum samples from a population-based study conducted in the Canary Islands, levels of 25(OH)D were analyzed. In 876 individuals who had no history of kidney or malabsorption disorders and who had not been treated with calcium and/or VitD supplementation, the median 25(OH)D level was 26.3 (5th;95th percentile, 14.3;45.8)ng/mL. Notably, 65.4% of the population had 25(OH)D blood levels below 30ng/mL, 23.4% below 20ng/mL and 6.4% below 15ng/mL. Based on the lack of evidence supporting causality between 25(OH)D levels below what is recommended as optimal (≥20ng/mL, or even ≥30ng/mL) and major skeletal and non-skeletal diseases, and in light of the distribution of the concentration of this vitamin in healthy adults living under optimal conditions of solar irradiation, it seems reasonable to consider 25(OH)D levels below 20ng/mL and close to 15ng/mL as adequate for the general population.

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

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.

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.

Lichen secondary metabolites are generally considered as repellent compounds for lichen feeders. Nevertheless, if the only food available consists in lichens rich in secondary metabolites, lichenophages such as Notodiscus hookeri, a gastropod native from the Possession Island, seem able to implement strategies to overcome the toxicity of these metabolites. Thus, the balance between phagostimulant nutrients and deterrent metabolites appears to play a key role in their feeding preferences. To further understand lichen-gastropod interactions, we studied the feeding behavior of Notodiscus hookeri fed exclusively with Usnea taylori, a lichen rich in usnic acid and arabitol. Snail feeding choice experiments with intact lichens vs acetone-rinsed lichens were carried out to study the influence of secondary metabolites. Simultaneously, usnic acid and arabitol were quantified and localized within the lichen thallus using HPLC-DAD-MS and in situ imaging by mass spectrometry to assess whether their spatial distribution induce preferential snail grazing. Then, no-choice feeding experiments were devised using usnic acid and arabitol embedded in artificial diet, separately or together. This case study demonstrated that the nutritional activity of N. hookerii was governed by the chemical quality of the food and primarily by nutrient availability (arabitol), despite the presence of deterrent metabolites (usnic acid).

Big Data classification has recently received a great deal of attention due to the main properties of Big Data, which are volume, variety, and velocity. The furthest-pair-based binary search tree (FPBST) shows a great potential for Big Data classification. This work attempts to improve the performance the FPBST in terms of computation time, space consumed and accuracy. The major enhancement of the FPBST includes converting the resultant BST to a decision tree, in order to remove the need for the slow K-nearest neighbors (KNN), and to obtain a smaller tree, which is useful for memory usage, speeding both training and testing phases and increasing the classification accuracy. The proposed decision trees are based on calculating the probabilities of each class at each node using various methods; these probabilities are then used by the testing phase to classify an unseen example. The experimental results on some (small, intermediate and big) machine learning datasets show the efficiency of the proposed methods, in terms of space, speed and accuracy compared to the FPBST, which shows great potential for further enhancements of the proposed methods to be used in practice.

In this paper, we investigate the effects of certain variants of the commutative laws on properties of several families of algebras which are in general not commutative, such as groups, linear algebras, or actually quite anti-commutative, such as $BCK$-algebras and $d$-algebras among others. From results obtained it becomes clear that by considering these variants in the presence of yet other axioms it is to be expected that a quite rich and varied set of results may be obtained both in the general and the particular setting of which what has been accomplished in this paper is a substantial sample.

Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder frequently associated with ulcerative colitis (UC). Patients with PSC and UC have higher risk of colorectal neoplasia than patients with UC without PSC. Oncogenic properties of micro RNA 346 (miR-346) have been recently reported. In this study we investigated expressions of miR-346 and its two target genes i.e. the receptor of vitamin D (VDR) and the tumor necrosis factor α (TNF-α), which are known to modulate carcinogenesis. Biopsies from ascending and sigmoid colon were obtained from patients with PSC with and without UC, patients with UC and healthy controls. MiR-346 expression was increased in ascending but not sigmoid colon of patients with PSC and UC when compared to other analyzed groups (p<0.001 for all). In patients with UC an exceptionally low colonic expression of miRNA-346 was accompanied by the increase in VDR expression, and the extensive upregulation of TNF-α gene which protein product is known to be cytotoxic to tumor cells at high concentration. In summary, a substantial upregulation of miRNA-346 in ascending colon of patients with PSC and UC may be responsible for the inhibition of VDR and TNF-α signaling -pathway which may result in an inadequate suppression of neoplasia.

Corona loss generated from conductors is one of the important design factors on ac transmission lines. Based on helical charge simulation method, the 3-D corona loss calculation model considering the conductors’ outer strands in the corona cage is established. With regard to 2-D corona-loss calculation method, the calculation model proposed in this paper can take the electric field strength’s nonuniformity along the axial direction of stranded conductor into consideration, furthermore, it can also calculate the corona loss when the conductor has sag. The calculation results of the LGJ-300/40 and LGJ-400/35 in the small corona cage well coincide with the measurement results, which indicates that the corona-loss calculation model is appropriate. In addition, the corona loss of the bundle conductors 4 × LGJ720 with sag in UHV corona cage is also analyzed.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

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.

The world is currently going through a serious pandemic of viral infection with SARS-CoV-2, a new isolate of coronavirus, resembling and surpassing the crisis that occurred in 2002 and 2013 with SARS and MERS, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and reaching more than 130 countries worldwide. The very large spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, alarming governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease 2019 (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of patients will need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of elderly individuals, especially those who are more than 60 years old and have comorbidities, including hypertension, diabetes and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow protected and not included as a risk group.Thus, here, we discuss some possibilities of molecular and cellular mechanisms by which elderly subjects may be more susceptible to severe COVID-19. In this sense, we raise two main points: i) increased ACE-2 expression in pulmonary and heart tissue of chronic angiotensin 1 receptor (AT1R) blocker users and hypertensive individuals and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe these are pivotal points for a better understanding of the pathogenesis of severe COVID-19 and must be addressed with attention by physicians and scientists in the field.

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

Human RAD51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. The activator protein Swi5-Sfr1 and Ca2+ ions stimulate different reaction steps and induce a perpendicular orientation of DNA bases in the presynaptic complex. To investigate the importance of base orientation in the strand exchange reaction, we examined the Ca2+ concentration dependence of strand exchange activities and structural changes in the presynaptic complex. Our results show that optimal D-loop formation (strand exchange with closed circular DNA) requires Ca2+ concentrations greater than 5 mM, while 1 mM is sufficient for strand exchange between two oligonucleotides. The structural change, which is evidenced by an increase in fluorescence intensity of poly(dεA) (a poly(dA) analog), reaches a plateau at 1 mM Ca2+. Meanwhile, the linear dichroism signal intensity at 260 nm, which is indicative of rigid perpendicular DNA base orientation, requires >2 mM Ca2+ for saturation and thus correlates with the stimulation of D-loop formation. Therefore, Ca2+ exerts two different effects. Thermal stability measurements suggest that HsRad51 binds two Ca2+ ions with KD values of 0.3 mM and 2.5 mM, implying that one step is stimulated by one Ca2+ bond and the other by two Ca2+ bonds. We further discuss the parallels between Mg2+ activation of RecA and Ca2+ activation of HsRad51.

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.

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.

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.

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.

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.

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.

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.

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.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

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.

Newly characterising 245 Italian and Albanian HCV-2 NS5B sequences collected between 2001 and 2016 was used to reconstruct the origin and dispersion pathways of HCV-2c. The tree of a subset of these sequences aligned with 247 publicly available sequences was reconstructed in spatio-temporal scale using the Bayesian approach, and the effective replication number (Re) was estimated using the birth-death model. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania, and that GT2 originated in Guinea Bissau in the XVI century and spread to Europe in the XX century. The HCV-2c subtype had two internal nodes respectively dating back to the 1930s and 1950s having as most probable locations Ghana and Italy, respectively. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in both Italy between the 1950s and 1980s, and Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonisation (1936-1941), but did not reach Albania until the period of dramatic migration to Italy in the 1990s.

The study aimed to explore the correlation among Angiopoietin-1, (Ang-1) and Angiopoietin-2, (Ang-2) concentrations and the Angiopoietin-2/Angiopoietin-1 ratio, (Ang-2/Ang-1) with clinical outcomes, potentially serving as disease severity and survival biomarkers. A study at AHEPA University Hospital involved 90 COVID-19 adult patients, with 30 hospitalized in intensive care and 30 in ward units and 30 asymptomatic non-hospitalized individuals as controls. Estimated endothelial dysfunction markers related to angiogenesis were measured, and statistical analysis was performed using IBM SPSS Statistics software, version 29. There was a statistically significant difference only between outpatient and hospitalized patients (non-ICU -ICU groups) for the Ang-1 and Ang-2 indexes. The Ang-2/Ang-1 ratio has differed significantly among all individual patient groups. A ROC analysis was conducted to find an optimal threshold for distinguishing (outpatients – non-ICU) and (non-ICU –ICU) groups. It was based on Youden's Index and was 0.1122 and 0.3825, respectively. The Ang-1, Ang-2 levels, and Ang-2/Ang-1 ratio were analysed as indicators for severity in COVID-19 patients. The Ang-2/Ang-1 ratio demonstrated more excellent prognostic and diagnostic utility than individual biomarker levels. Monitoring the Ang-2/Ang-1 ratio can identify COVID-19 patients at risk and assist clinicians in tailoring treatment strategies for improved outcomes.

The thionamide antithyroid drugs were discovered largely following serendipitous observations by numerous researchers in the 1940s who found that sulfhydryl-containing compounds were goitrogenic in animals. Prof. Edwin B. Astwood was the first to use these compounds to treat hyperthyroidism. In this review, we summarize the history of the development of these drugs and the coordination possibility of 2-thiouracil and its derivatives, as well as the biological activities of some of its complexes. Some of them are used as agents for the treatment of tuberculosis, and arthritis, others have bactericidal and fungicidal activity, the third cytotoxic properties, and could be used to treat various types of cancer.

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

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

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.

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

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.

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.

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.

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 3D reconstruction method using RGB-D camera has a good balance in hardware cost, point cloud quality and automation. However, due to the limitation of inherent structure and imaging principle, the acquired point cloud has problems such as a lot of noise and difficult registration. This paper proposes a three-dimensional reconstruction method using Azure Kinect to solve these inherent problems. Shoot color map, depth map and near-infrared image of the target from six perspectives by Azure Kinect sensor. Multiply the 8-bit infrared image binarization with the general RGB-D image alignment result provided by Microsoft to remove ghost images and most of the background noise. In order to filter the floating point and outlier noise of the point cloud, a neighborhood maximum filtering method is proposed to filter out the abrupt points in the depth map. The floating points in the point cloud are removed before generating the point cloud, and then using the through filter filters out outlier noise. Aiming at the shortcomings of the classic ICP algorithm, an improved method is proposed. By continuously reducing the size of the down-sampling grid and the distance threshold between the corresponding points, the point clouds of each view are continuously registered three times, until get the complete color point cloud. A large number of experimental results on rape plants show that the point cloud accuracy obtained by this method is 0.739mm, a complete scan time is 338.4 seconds, and the color reduction is high. Compared with a laser scanner, the proposed method has considerable reconstruction accuracy and a significantly ahead of the reconstruction speed, but the hardware cost is much lower and it is easy to automate the scanning system. This research shows a low-cost, high-precision 3D reconstruction technology, which has the potential to be widely used for non-destructive measurement of crop phenotype.

Cathepsin D (CatD; EC 3.4.23.5) family peptidases of parasitic organisms are regarded as potential drug targets as they play critical roles in the physiology and pathobiology of parasites. Previously, we characterized the biochemical features of cathepsin D isozyme 2 (CatD2) in the carcinogenic liver fluke Clonorchis sinensis (CsCatD2). In this study, we performed all-atomic molecular dynamics simulations by applying different systems for the ligand-free/bound forms under neutral and acidic conditions to investigate the pH-dependent structural alterations and associated functional changes in CsCatD2. CsCatD2 showed several distinctive characteristics as follows: 1) CsCatD2-inhibitor complex formed more hydrogen bonds; 2) acidic pH caused major conformational transitions from open to closed state in this enzyme; 3) neutral pH induced displacement of the N-terminal part to hinder the accessibility of the active site and open allosteric site of this enzyme; and 4) the flap dynamics metrics, including distance (d1), TriCα angles (θ1 and θ2), and dihedral angle (ϕ), account for the asymmetrical twisting motion of the active site of this enzyme. These findings provide an in-depth understanding of the pH-dependent structural dynamics of CsCatD2 and basic information for the rational design of an inhibitor as a drug targeting CsCatD2.

At present, the world is at the peak of production of traditional fossil fuels. Much of the resources that humanity has been consuming (oil, coal and natural gas) are coming to an end. The human being faces a future that must necessarily go through a paradigm shift, which includes a progressive movement towards increasingly less polluting and energetically viable resources. In this sense, nanotechnology has a transcendental role in this change. For decades, new materials capable of being used in energy processes have been synthesized that undoubtedly will be the cornerstone of the future development of the planet. In this review, we report on the current progress in the synthesis and use of one-dimensional (1D) nanostructured materials (specifically nanowires, nanofibers, nanotubes and nanorods), with compositions based on oxides, nitrides, or metals, for applications related to energy. Due to its extraordinary surface-volume relationship, tunable thermal and transport properties, and its high surface area, these 1D nanostructures have become fundamental elements for the development of energy processes. The most relevant 1D nanomaterials, their different synthesis procedures, and useful methods for assembling 1D nanostructures in functional devices will be presented. Applications in relevant topics such as optoelectronic and photochemical devices, hydrogen production or energy storage, among others, will be discussed. The present review concludes with a forecast on the directions towards which future research could be directed on this class of nanostructured materials.

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).

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.

This study investigated the factors affecting consumers’ acceptance to use cashless payment services in Malaysia through the construction of the Cashless Society Acceptance (CSA) model. The Technology Readiness Index 2.0 and Unified Theory of Acceptance and Use of Technology 2 were employed to create the CSA model. A total of 434 questionnaires were collected from Malaysian consumers, aged 18 years and above. The results show that Perceived Usefulness, Perceived Ease of Use, and Discomfort have the most significant influence on the consumers’ acceptance of cashless payment services with R-square of 71.4%.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

This paper is devoted to the study of reproducing kernels on 2-inner product Hilbert spaces. We focus on a new structure to produce reproducing kernel Hilbert and Banach spaces. According to multi-variable computing, this structures can be useful in electrocardiographs, machine learning and economy

In this work, we introduce the concepts of r-fuzzy soft δ-open (resp. semi-open and α-open) sets on fuzzy soft topological space, the relations of these sets with each other are established. Next, we introduce the concepts of fuzzy soft δ-continuous (resp. β-continuous, semi-continuous, pre-continuous and α-continuous) functions, and some properties of these functions along with their mutual relationships are investigated. Also, a decomposition of fuzzy soft semi-continuity and a decomposition of fuzzy soft α-continuity are given. Finally, as a weaker form of fuzzy soft continuity by Aygunoglu et al. (2014), the concepts of fuzzy soft almost (resp. weakly) continuous functions are introduced, and some properties are specified. Moreover, we explore the notion of continuity in a very general setting namely fuzzy soft (L, M, N, O)-continuous functions, and a historical justification are obtained.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes Angiotensin Converting Enzyme 2 (ACE2) as its main receptor for cell entry. We have bioengineered a soluble ACE2 protein termed ACE2 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here we investigated the protective effect of this protein when administered intranasally to k18-hACE2 mice infected with the aggressive SARS-CoV-2 delta variant. k18-hACE2 mice were infected with the SARS-CoV-2 delta variant by inoculation of a lethal dose (2x104 PFU) and followed for up to 14 days. ACE2-618-DDC-ABD (10mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 hours post viral inoculation. All animals in the PBS-control group had succumbed to the disease on day 7 post infection (0% survival) whereas, by contrast, there was only one casualty in the group that received ACE2-618-DDC-ABD (90% survival). Mice in the ACE2-618-DDC-ABD group had minimal disease as assessed by a clinical score and stable weight and both brain and lung viral titers were markedly reduced. These findings demonstrate the efficacy of a bioengineered soluble ACE2 decoy with extended duration of action in protecting against the aggressive delta SARS-CoV-2 variant. Together with previous work these findings demonstrate the universal protective potential against current and future emerging SARS-CoV-2 variants.

The treatment of viral infections is challenging owing to the intricate structure and metabolism of the viruses. In addition, they can highjack host cellular metabolism, mutate and adapt to harsh environmental conditions. The novel coronavirus (SARS-CoV-2) displays further resilient attributes, making its eradication even more difficult. SARS-CoV-2 is an enveloped virus whose replication can be targeted by limiting the substrates available for structural incorporation. One such molecule that limits substrate availability and has received much attention lately is 2-Deoxy-d-glucose (2-DG). SARS-CoV-2 infection induces glycolysis, impairs mitochondrial function, and damages the infected cells. Administration of 2-DG can inhibit increased glycolytic flux and some other metabolic processes to cause the cessation of viral replication. This article provides a review of the mechanism of action and safety concerns associated with administering 2-DG in the treatment of COVID-19. The drug can have adverse effects on normal cell metabolism since it targets cells non-selectively, possibly in a dose-dependent manner. In addition, the drug has limited use in SARS-CoV-2 infection associated with stroke, hypoxic-ischemic encephalopathy, and critical illness.

Since December 2019, the worldwide spread of COVID-19 has brought the majority of the world to a standstill, affecting daily lives as well as economy. Under these conditions, it is imperative to develop a cure as soon as possible. On account of some of the adverse side effects of the existing conventional drugs, researchers all around the world are screening natural antiviral phytochemicals as potential therapeutic agents against COVID-19. This paper aims to review interactions of some specific phytochemicals with the receptor binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2 and suggest their possible therapeutic applications. Literature search was done based on the wide array of in-silico studies conducted using broad spectrum phytochemicals against SARS-CoV-2 and other viruses. We shortlisted 26 such phytochemicals specifically targeting the S protein and its interactions with host receptors. To validate the previously published results, we also conducted molecular docking using the AutoDockVina application and identified 6 high potential phytochemicals for therapeutic use based on their binding energies. Besides this, availability of these compounds, their mode of action, toxicity data and cost-effectiveness were also taken into consideration. Our review specifically identifies 6 phytochemicals that can be used as potential treatments for COVID-19 based on their availability, toxicology results and low costs of production. However, all these compounds need to be further validated by wet lab experiments and should be approved for clinical use only after appropriate trials.

SARS-CoV-2, the novel coronavirus behind COVID-19 pandemic is acquiring new mutations in its genome. Although some mutations provide benefits to the virus against human immune response, a number of them may result in their reduced pathogenicity and virulence. By analyzing more than 3000 high-coverage, complete genome sequences deposited in the GISAID database, here I report a unique 28881-28883:GGG>AAC trinucleotide-bloc mutation in the SARS-CoV-2 genome that results in two sub-strains, described here as SARS-CoV-2g (28881-28883:GGG genotype) and SARS-CoV-2a (28881-28883:AAC genotype). Computational analysis and literature review suggest that this bloc mutation would bring 203-204:RG(arginine-glycine)>KR(lysine-arginine) amino acid changes in the nucleocapsid (N) protein affecting the SR (serine-arginine)-rich motif of the protein, a critical region for the transcription of viral RNA and replication of the virus. Thus, 28881-28883:GGG>AAC bloc-mutation is expected to modulate the pathogenicity of the SARS-CoV-2. Remarkably, SARS-CoV-2g and SARS-CoV-2a strains can be linked with the heterogeneity of COVID-19 cases across different regions within and between countries by analyzing existing data. Sequence analysis suggests that severely affected cities, such as Milan, Lombardy, New York, Paris have the predominant presence of SARS-CoV-2g strains, whereas less affected places like Abruzzo, Lyon, Valencia have a relatively higher presence of SARS-CoV-2a, an indication that the latter strain may contribute to the reduced cases of COVID-19. A similar relationship is observed when Netherlands, Portugal are compared with Spain, France and Germany. These analyses suggest that the SARS-CoV-2 has already evolved into a less infective SARS-CoV-2a affecting COVID-19 cases in different regions. The time a country or region needs to acquire SARS-CoV-2a strains may be indicative to the time it would need to overcome the peak of the COVID-19 cases. To confirm these assumptions, prompt retrospective and prospective epidemiological studies should be conducted in different countries to understand the course of pathogenicity of the SARS-CoV-2a and SARS-CoV-2g. Potential drugs can be designed targeting 28881-28883 region of the N protein to modulate virus pathogenicity.

This case study focuses on exploring the potential of biogas as a direct substitute for conventional fossil fuels in industrial applications. Instead of being limited to its common uses as a vehicle fuel or for power generation, this research aims to investigate how biogas can be integrated into industrial processes as an advanced and sustainable energy solution. By conducting a detailed analysis of the financial implications associated with the utilization of landfill gas and gas derived from biomass, a comprehensive understanding of their practical applications in the industrial sector can be obtained. This research goes beyond a superficial examination and delves into the intricate aspects of incorporating biogas as a viable alternative fuel source. When we say that utilizing biogas is technically feasible, it means that the necessary infrastructure and technologies are available to support its integration into industrial processes. This implies that there are existing methods and systems in place that can efficiently harness and utilize biogas for various industrial applications. These technologies ensure a seamless transition from conventional fossil fuels to renewable energy sources, leading to a more sustainable and environmentally friendly industrial landscape. Moreover, the statement that utilizing biogas is economically feasible emphasizes that the financial viability of employing biogas in industrial processes is advantageous. This research explores the potential cost savings and benefits associated with substituting conventional fuels with biogas. By carefully examining the economic aspects, such as initial investments, operational costs, and potential revenue streams, a comprehensive understanding of the financial impact of adopting biogas solutions in the industrial sector can be gained. By expanding and broadening the understanding of the technical and economic feasibility of biogas integration, this research aims to provide valuable insights into the potential of advanced biogas solutions for industrial applications. Indeed, to make biogas a viable and sustainable option as a raw material, it is necessary to establish farming subsidies and financial support specifically tailored for biogas production, similar to the existing support provided for food production. These subsidies and financial incentives play a crucial role in promoting and encouraging the growth of the biogas industry. By establishing such support systems, farmers and other stakeholders in the agricultural sector can be incentivized to participate in the production of biogas. This can involve the utilization of agricultural waste, organic residues, or dedicated energy crops for biogas generation. The financial assistance can help offset the initial investment costs, provide incentives for production, and ensure the economic viability of biogas projects. Moreover, when considering large-scale landfills or situations where industrial demands for energy are relatively low, landfill gas becomes a viable and practical option. Landfill gas, which is generated by the decomposition of organic waste in landfills, can be harnessed and utilized for various industrial purposes. This not only helps in managing waste but also provides a valuable source of renewable energy. In summary, while farming subsidies and financial support are crucial for promoting biogas production, landfill gas remains a viable option for large landfills or situations with minor industrial demands. The combination of these two approaches offers a comprehensive outlook on utilizing biogas as a renewable energy source for industrial applications.

This paper presents ensemble learning of multi-source satellite sensors dataset to obtain better predictive performance of the forest biomass. Spectral, spectral-indices, and spectral-textural features were generated from two optical satellite sensors, Landsat 8 Operational Land Imager (OLI) and Sentinel-2 Multispectral Instrument (MSI). In addition, two radar satellite sensors, Sentinel-1 C-band Synthetic Aperture Radar (CSAR), and Advanced Land Observing Satellite (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) were utilized to generate backscattering and backscattering-textural features. The plot-wise above ground biomass data available from five forests in New England region were utilized. Ensemble learning of multi-source satellite sensors dataset was carried out by employing four machine learning regressors namely, Support Vector Machines (SVM), Random Forests (RF), Gradient Boosting (GB), and Multilayer Perceptron (MLP). A five-fold cross-validation method was used to evaluate predictive performance of the multi-source satellite sensors. The integration of multi-source satellite features, comprising of spectral, spectral-indices, backscattering, spectral-textural, and backscattering-textural information, through ensemble learning and cross-validation approach implemented in the research showed promising results (R² = 0.81, RMSE = 46.2 Mg/ha) for the estimation of plots-level forest biomass in New England region.

Green credit policy as an important tool to guide China's sustainable economic development, how to effectively play the function of capital deployment and improve the efficiency of industrial green innovation is an important issue facing the construction of ecological civilization. This paper uses China's Green Credit Guideline introduced in 2012 as a quasi-natural experiment , based on relevant panel data of industries from 2007 to 2018, uses the Super-SBM model including non-expected output to measure the green innovation efficiency of 35 industries in China, and constructs the PSM-DID model to explore how green credit policy impact on the green innovation efficiency of heavily polluted industries, the results show that : green credit policy significantly contributes to green innovation efficiency of heavily polluted industries with a lag. Further study finds that green credit policy pushes heavily polluted industries to improve green innovation efficiency by increasing financing cost and R&D investment; meanwhile, the heterogeneity test shows that the higher the state-owned share of industry, the greater the promoted effect of green credit policy on green innovation efficiency of heavily polluted industries. Finally, in order to accelerate the implementation of green credit policy and promote the green innovation efficiency of heavily polluted industries, relevant countermeasures are proposed from three aspects: banks, enterprises and government.

Fractal behavior and long-range dependence are widely observed in measurements and characterization of traffic flow in high-speed computer networks of different technologies and coverage levels. This paper presents the results obtained when applying fractal analysis techniques on a time series obtained from traffic captures coming from an application server connected to the Internet through a high-speed link. The results obtained show that traffic flow in the dedicated high-speed network link have fractal behavior when the Hurst exponent is in the range of 0.5, 1, the fractal dimension between 1, 1.5, and the correlation coefficient between –0.5, 0. Based on these results, it is ideal to characterize both the singularities of the traffic and its impulsiveness during a fractal analysis of temporal scales. Finally, based on the results of the time series analyses, the fact that the traffic flows of current computer networks exhibit fractal behavior with a long-range dependency is reaffirmed.

Due to the continuous trade friction between China and the United States, for domestic enterprises in China, the cost of importing foreign technologies is increasing. Thus, the independent research and development (R&D) becomes particularly important for the realization of green technology innovation (GTI). This paper establishes a non-linear mediating effect model based on the data of various regions in China from 2012 to 2018. The main results are shown in the following. Firstly, there is an inverted U-shaped relationship between the intensity of intellectual property protection (IPP) and the level of GTI. Furthermore, the independent R&D investment has a masking effect between them. Secondly, by taking the independent R&D investment as a threshold variable, we prove our findings. Considering that the intensity of IPP is at a high level in most regions of China, the above statements mean that the enterprises need to continuously increase their investment in R&D, in order to further improve the regional ability in GTI. Meanwhile, local governments should also stimulate enterprises' willingness to expand their scale in R&D by issuing incentive policies, such as R&D tax incentives and government subsidies.

This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.

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.

Waste orange peel represents a heavy burden for the orange juice industry, estimated in several million tons per year worldwide; nevertheless, this by-product is endowed with valuable bioactive compounds, such as pectin, polyphenols and terpenes. The potential value of the waste orange peel has stimulated the search for extraction processes, alternative or complementary to landfilling or to the integral energy conversion. This study introduces controlled hydrodynamic cavitation processes, as a new route to the integral valorization of this by-product, based on simple equipment, speed, effectiveness and efficiency, scalability, and compliance with green extraction principles. Waste orange peel, in batches of several kg, was processed in more than 100 L of water, absent any other raw materials, in a device comprising a Venturi-shaped cavitation reactor. The extractions of pectin, endowed with a very low degree of esterification, polyphenols (flavanones and hydroxycinnamic acid derivatives), and terpenes (mainly d-limonene) were effective and fast (high yield, few min of process time), as well as the biomethane generation potential of the process residues was effectively exploited. The achieved results proved the viability of the proposed route to the integral valorization of waste orange peel, though wide margins exist for further improvements.

Designing motion representations for the problem of 3D human action recognition from skeleton sequences is an important yet challenging task. An effective representation should be robust to noise, invariant to viewpoint changes and result in a good performance with low-computational demand. Two main challenges in this task include how to efficiently represent spatio-temporal patterns of skeletal movements and how to learn their discriminative features for classification task. This paper presents a novel skeleton-based representation and a deep learning framework for 3D action recognition using RGB-D sensors. We propose to build an action map called SPMF (Skeleton Posture-Motion Feature), which is a compact image representation built from skeleton poses and their motions. An Adaptive Histogram Equalization (AHE) algorithm is then applied on the SPMF to enhance their local patterns and form an enhanced action map, namely Enhanced-SPMF. For learning and classification tasks, we exploit Deep Convolutional Neural Networks based on the DenseNet architecture to learn directly an end-to-end mapping between input skeleton sequences and their action labels via the Enhanced-SPMFs. The proposed method is evaluated on four challenging benchmark datasets, including both individual actions, interactions, multiview and large-scale datasets. The experimental results demonstrate that the proposed method outperforms previous state-of-the-art approaches on all benchmark tasks, whilst requiring low computational time for training and inference.

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.

The synthesis and structure of the 4,4′-dipyridyl N,N′-donor ligand with a central thiazolo[5,4-d]thiazole (tztz) unit, named Dptztz is presented. With the linker Dptztz and isophthalate (benzene-1,3-dicarboxylate, 1,3-BDC²⁻) the mixed-linker, two-dimensional coordination network [Zn(1,3-BDC)Dptztz]·DMF could be obtained (DMF = dimethylformamide), which belongs to the class of coordination polymers with interdigitated structures (CIDs). The incorporated DMF solvent molecules can be removed through solvent exchange and evacuation such that the supramolecular 3D packing of the 2D networks retains porosity for CO₂ adsorption in activated [Zn(1,3-BDC)Dptztz]. The first sorption study of a tztz-functionalized porous metal-organic framework material yields a BET surface of 417 m²/g from CO₂ adsorption. The heat of adsorption for CO₂ exhibits a relative maximum with 27.7 kJ/mol at adsorbed CO₂ of about 4 cm³/g STP which is interpreted as a gate-opening effect.

Understanding the dynamics of humoral immune responses throughout the COVID-19 pandemic is crucial for optimizing vaccine strategies. This study aimed to investigate the impact of infection and vaccine-induced immunity on the Albanian population from August 2021 to August 2022. Two independent samples from the Albanian general population were analyzed using an ELISA method to assess IgG class anti-Spike (S1) and anti-Nucleocapsid (N) SARS-CoV-2 antibodies. The results revealed a robust immune response among vaccinated individuals with prior COVID-19 infection who received only one vaccine dose. In the 2022 cohort, most individuals who received one vaccine dose achieved comparable seropositivity and antibody levels to those who received two doses. However, individuals aged 61 and over required two or three vaccine doses to reach the same level of immune response as the younger population. Notably, the time elapsed since infection or vaccination did not significantly impact the immune response. These findings highlight the importance of hybrid immunity and suggest that one vaccine dose may be sufficient for most individuals with prior COVID-19 infection. However, additional doses are necessary for optimal protection in older individuals. This study provides unique insights into humoral immune response dynamics that can be used to refine ongoing COVID-19 population vaccination strategies for middle-income countries with low vaccination coverage.