SiO2-SO3H, with a surface area of 115 m2/g, pore volume of 0.38 cm3g-1 and 1.32 mmol H+/g, was used as a 20% w/w catalyst for the preparation of methyl salicylate (Wintergreen oil or MS) from acetylsalicylic acid (ASA). A 94% conversion was achieved in a microwave reactor during 40.0 minutes at 120 oC in MeOH. The resulting crude product was purified by flash chromatography. The catalyst could be re-used three times.

The aim of this work was the study and evaluation of winery by-products in the framework of circular bioeconomy. Grape seeds and grape skins from Greek traditional Ionian Islands varieties were analyzed in an attempt to provide the appropriate basis for model development of their sustainable exploitation at a local or regional level. The wastes collected directly from the wineries immediately after the vinification process and analyzed by chromatographic and spectroscopic techniques. Also, annual production and yields were estimated. Grape seed oil quality was evaluated based on fatty acid methyl esters (FAMEs) composition. Grape skins phenolic fraction was extracted by an eco-friendly, non-toxic water-glycerol solvent system and were detected qualitatively. Also, total phenolic content (TPC) and antioxidant activity were measured. Based on estimated yields, our results demonstrate that winery by-products have the potential to promote the cyclical bioeconomy in a modern economic growth model that will reduce waste, and environmental costs as they can be reused as whole material in foods, dietary supplements, cosmetic ingredients, food colorants and preservatives.

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.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a-3i) exhibited significant clot lysis with respect to negative control and reference drug streptokinase (30,000 IU) while enhanced clotting time (CT) values were observed (130-342 sec) for these tested compounds than the standard drug heparin (110 sec.). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d and 3h) than the control ligand RPR200095. In addition, very good inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612-6270) with ACE values (–189.68 to –352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE –197.81 kcal/mol. In vitro, in vivo and in silico results proposed that these newly synthesized compounds can be used as anti-coagulant agents.

The main objective of this study is to analyze the impact of investment in Research & Development on the performance and value of companies, that is, to try to explain how R&D investment influences the companies’ performance. For this purpose, a dynamic panel data model was estimated using the Generalized Method of Moments, which made possible to measure the impact of R&D investment on performance through the Return on Operating Assets ratio for the Portuguese companies that invested the most between 2012 to 2019. The results show that the investment in R&D is not statistically significant in explaining the operating return on assets. However, the lagged financial performance in one period, the leverage, the asset turnover ratio and the accounts payable turnover show to have impact on the variable under study.

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.

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

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.

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered as one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by two tests by measuring cell viability (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment have a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski's rule of thumb of five (RO5), which increases their chances for possible use as orally active drugs with a good ability to absorption and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential.

In this study, a high energy conversion efficient dye-sensitized solar cells (DSSC) was successfully fabricated by attaching a double anti-reflection (AR) layer which is composed of a subwavelength moth-eye structured polymethyl methacrylate (PMMA) film and a polydimethylsiloxane (PDMS) film. The efficiency is up to 6.79%. The moth-eye structured PMMA film was fabricated by using anodic aluminum oxide (AAO) template which is simple, low-cost and scalable. The nano-pattern of AAO template has been precisely reproduced onto PMMA film. The photoanode is composed of Titanium dioxide (TiO₂) nanoparticles (NPs) with diameter of 25 nm deposited on the fluorine-doped tin oxide (FTO) glass substrate and the sensitizer N3. The double AR layer can effectively improve the short-circuit current density (JSC) and conversion efficiency from 14.77 to 15.79 mA/cm² and from 6.26% to 6.79%, respectively.

In this work, a GaN-on-Si quasi-vertical Schottky diode was demonstrated on a locally grown n-GaN drift layer. The diode achieves a high current density of 2.5 kA/cm², a specific on-resistance RON,sp of 1.9 mΩ.cm² despite the crowding effect in quasi-vertical device and on/off current ratio (Ion/Ioff) of 1010. Temperature-dependent current-voltage characteristics have been measured in the range of 300-433 K to investigate the mechanisms of leakage conduction in the device. At near zero bias, thermionic emission (TE) was found to dominate. At voltage range from -1 to -10 V, electrons gain enough energy to excite into trap states, leading to the dominance of Frenkel-Poole emission (FPE). For a higher voltage range (-10V to -40V), the increased electric field promotes electron hopping along the threading dislocations in the “bulk” GaN layers, and thus, Variable Range Hopping becomes the main mechanism for the whole temperature range. This work provides an in-depth insight into the leakage conduction mechanisms on vertical GaN-on-Si Schottky barrier Diodes (SBDs) grown by localized epitaxy.

Glycosylation, the most significant modification of proteins, plays an essential role in cellular processes. Congenital disorders of glycosylation (CDG) are multisystemic diseases resulting from mutations affecting glycosylation steps. Diagnosis of CDG relies on biochemical assays, such as isoelectric focusing. Despite its significance, CDG cases remain unreported in Cuba due to the lack of implemented diagnostic methods. This study aimed to evaluate transferrin glycoforms for diagnosing congenital N-glycosylation defects. We conducted a cross-sectional descriptive study using serum samples from 17 patients stored at the National Center for Medical Genetics of Cuba for suspected CDG. Results revealed abnormal glycosylation patterns in 7 patients, suggesting congenital N-glycosylation defects. We conclude that the implementation of transferrin glycoform analysis could pioneer a preliminary diagnosis of CDG in Cuba.

In the past few decades, N-heterocyclic carbenes (NHCs) open the new field of organocatalysis in synthetic organic chemistry. This review highlights the dramatic progress in the NHC-catalyzed C−O bond formation based on the activation of aldehyde C(sp2)−H bonds. The oxidative and redox transformations for the synthesis of various molecules with structural diversity and complexity are summarized. Furthermore, new methods and strategies for NHC catalysis are emerging continuously; thus, cooperative catalysis with Brønsted acid, hydrogen-bonding catalyst, transition-metal catalyst, and photocatalyst is also described.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

One of the most concerning global environmental issues is the pollution of agricultural soils by heavy metals (HMs), especially cadmium (Cd), which not only affects human health by taking Cd-containing foods but also impacts the quality of rice. The soil's nitrification and denitrification processes, coupled with the release of volatile organic compounds by plants, raise substantial concerns. The understanding of three aspects of paddy soil under conditions of heavy-metal pollution and water management is currently limited. In this review, we summarized recent literature related to the deleterious effects of Cd on both soil processes related to the N cycle and rice quality, particularly aroma, in different water management practices. Under both continuous flooding (CF) and alternate wetting and drying (AWD) conditions, cadmium (Cd) has been observed to reduce both nitrification and denitrification processes. The adverse effects are more pronounced in continuous flooding (CF) compared to alternate wetting and drying (AWD). Similarly, the alteration in rice aroma is more significant in AWD than in CF. The precise modulation of volatile organic compounds (VOCs) by Cd, remains unclear based on the available literature. Nevertheless, HM accumulation is higher in AWD conditions compared to CF, leading to a detrimental impact on volatile organic compounds (VOCs). The literature concluded that AWD practices should be avoided in Cd contaminated fields to decrease accumulation and maintain the quality of rice. In the future, rhizospheric engineering and plant biotechnology can be used to decrease the transport of HMs from the soil to the plant’s edible parts.

Melittin, a natural antimicrobial peptide, displays a broad-spectrum antimicrobial activity, which has caused increasing attention as a potential antibiotic alternative. However, melittin has not been used widely at present due to its high hemolysis and low proteolytic stability. In this study, N-terminal fatty acid was conjugated to melittin to develop new melittin-derived lipopep-tides (MDLs) for improving the limitation of melittin. Our results showed that, the antimicrobial activity of MDLs was increased by 2 to 16 times compared with native melittin, and the stability of these MDLs against trypsin and pepsin degradation was increased by 50 to 80%. Besides, the hemolytic of the MDLs decreased when the length of the carbon chain of fatty acids exceeded 10. Among them, the newly designed analog Mel-C8 showed optimal antimicrobial activity and protease stability. The antimicrobial mechanism studied revealed that the MDLs showed a rapid bactericidal effect by interacting with LPS or LTA and penetrating the bacterial cell membrane. In conclusion, we designed and synthesized a new class of MDLs with potent antimicrobial activity, high proteolytic stability, and low hemolysis through N-terminal fatty acid conjugation.

Following on from work already carried out in our laboratory on a new biomass-derived green solvent, eucalyptol, we are now turning our attention to sabinene as a new green solvent. Sabinene is also derived from biomass. We have shown that it can be used as such or distilled to synthesize thiazolo[5,4-b]pyridine heterocycles by thermal or microwave activation. This new solvent was compared with various conventional and green solvents. The conditions were optimized to enable us to carry out the syntheses in good yields, and we were able to show that sabinene, a natural bicyclic monoterpene, could be used effectively as a solvent.

In the study of rough sets, there are many covering approximation spaces, how to classify covering approximation spaces has become a hot issue. In this paper, we propose concepts covering approximation $T_{1}$-space, $F-$symmtry, covering rough continuous mapping, covering rough homeomorphism mapping to solve this question. We also propose a new method for constructing topology in Theorem 5.1, and get the following properties: (1) For each $x\in U$, $\{X_{i}:i\in I\}\subseteq \mathcal{P}(U)$ is all the subsets of $U$ which contains $x$ and $*$ is a reflexive relation on $U$. If $V\in \tau$ is a subset of $U$ and $x\in V$, then $\underline{*}(\bigcap \limits_{i\in I}X_{i})$ is the smallest subset of $U$ and $x \in \underline{*}(\bigcap \limits_{i\in I}X_{i})\subseteq V$. Denoted by $C(x)=\bigcap \{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$. (2)If $V\in \tau$ is a subset of $U$, then $V =$ $\bigcup \limits_{x\in V} C(x)$. (3) Let $\{\underline{*}(X_{i}):x\notin \underline{*}(X_{i}), i\in I\}$, then $\overline{\{x\}}$ $=$ $U \setminus \bigcup \limits_{x\notin \underline{*}(X_{i}), i\in I}\underline{*}(X_{i})$; (4) Let $*$ be a reflexive relation on $U$. For every $X\subseteq U$, we have $int(\underline{*}(X))=\underline{*}(X)$. Where $int(\underline{*}(X))$ represents the interior of $\underline{*}(X)$. (5) Let $\{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$ be a family subsets of $U$, then $\{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$ is a base for $(U,\tau)$ at the point $x$. \\

The inability to efficiently metabolize homocysteine (Hcy), which occurs in nutritional and genetic deficiencies, leads to hyperhomocysteinemia (HHcy) thereby causing endothelial dysfunction, a hallmark of atherosclerosis which underpins cardiovascular disease (CVD). The dysregulation of mammalian target of rapamycin (mTOR) signaling, and impaired autophagy play important roles in CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites, Hcy-thiolactone (HTL) and N-Hcy-protein (N-Hcy). However, whether these metabolites can dysregulate mTOR signaling and autophagy in endothelial cells is not known. Here, we examined the influence of HTL, N-Hcy, and Hcy on the PHF8/H4K20me1/mTOR/autophagy pathway in human umbilical vein endothelial cells (HUVEC). We found that treatments with HTL, N-Hcy, or Hcy significantly reduced PHF8 protein and mRNA expression, increased H4K20me1, and upregulated mTOR signaling. Autophagy was also impaired (significantly downregulated BECN1, ATG5, ATG7, and LC3 protein and mRNA levels). We also found that these changes were mediated by PHF8-targeting microRNA (miR): miR-22-3p and miR-1229-3p. The effects of HTL, N-Hcy, or Hcy on the miR expression and on the PHF8/H4K20me1/mTOR/autophagy pathway were abrogated by treatments with an inhibitor of miR-22 or miR-1229. Taken together, these findings show that Hcy metabolites can upregulate miR-22-3p and miR-1229-3p expression, which then dysregulate the PHF8/H4K20me1/mTOR/autophagy pathway, important for vascular homeostasis.

Rechargeable aqueous Zn-ion batteries (ZIBs) have attracted considerable attention owing to their high theoretical capacity of 820 mA h g‒1, low cost and intrinsic safety. However, the electrolyte leakage and the instability issues of Zn negative electrodes originating from side reactions between the aqueous electrolyte and Zn negative electrode, not only restricts the battery stability but also results in short-circuit of aqueous ZIBs. Herein we report a flexible and stable N-isopropylacrylamide/sodium alginate (N-SA) gel electrolyte, which possesses high mechanical strength and high ionic conductivity of 2.96×10‒2 S cm‒1, and enables the Zn metal negative electrode and MnO2 positive electrode to reversibly and stably cycle. Compared to the liquid electrolyte, the N-SA hydrogel electrolyte can effectively form a uniform Zn deposition and suppress the generation of irreversible by-products. The assemble symmetric Zn/Zn cells at a current density of 1 mA cm‒2 shows a stable voltage profile, which maintains a low level of about 100 mV over 2600 h without an obvious short circuit or any overpotential increasing. Specially, the assembled Zn/N-SA/MnO2 batteries can deliver a high specific capacity of 182 mAh g‒1 and maintain 98% capacity retention after 650 cycles at 0.5 A g‒1. This work provides a facile method to fabricate high-performance SA-based hydrogel electrolytes that illustrates their potential for flexible batteries for wearable electronics.

In this paper, new N-way Wilkinson power dividers (WPDs) are represented by using slow-wave structures such as narrow slits loaded and meandered transmission lines. The slit loaded and meandered lines are used to represent the quarter wavelength transmission lines of a conventional WPD for size reduction. Based on the proposed approaches, 2-, 4- and 8-way power dividers are designed, simulated and fabricated. The fabricated -, 4- and 8-way circuits have been measured at the center frequencies of 2.03, 1.77, and 1.73 GHz in an excellent agreement with the predicted ones. The meandered transmission lines are also used to design new types of WPDs having novel input/output port arrangements. For this purpose, two 3-way WPDs are located at both sides of the same board so as to have different power splitting ratios at different inputs and outputs to provide alternative solutions for antenna arrays. Furthermore, a 5-way dual layer WPD is introduced by locating the meandered transmission lines to two layers. The proposed 3- and 5-way WPDs allow halving the input power at the next output port in the order of P/2, P/4, P/8, P/16, and P/16. All of the designed power halving WPDs have been simulated, fabricated and successfully tested.

To study the influence of electrothermal effect of ESD protection device on the reliability of inte-grated circuit,a theoretical model of ESD protection device thermal resistance is constructed in the paper based on the Conservation of Energy Principle. By analyzing the temperature relativity between electricity parameter and thermology parameter of ESD protection device characterized by self-heating thermal resistance, the quantitative relationship expression of physical parameter and geometric parameter is obtained, which can be used to improve ESD protection device elec-tro-thermal effect. The simulation testing and the real tape-out testing of ESD protection device self-heating thermal resistance based on ggNMOS are shown and compared. It is concluded that self-heating thermal resistance is an effective index for the protection device electrothermal char-acterization. Based on the established model, the self-heating thermal resistance could be decreased to improve the homogeneity of the heat transference. The uneven distribution of device temperature can be reduced, and the overall reliability of chips can be improved.

A new spirurid nematode Protospirura canariensis n. sp., parasite of the black rat Rattus rattus (Rodentia: Muridae) in El Hierro Island (Canary Archipelago, Spain) is described by means of light (LM) and scanning electron microscopy (SEM). The most discriminant characteristics between the new species and the existing species in the genus Protospirura are: (a) the number of tooth-like prominences in the submedian and lateral lobes of pseudolabia, both in males and females (2 and 4, respectively), (b) the size of right and left spicules in males (643–715 µm and 309–412 µm, respectively), and (c) the number and arrangement of cloacal papillae in males. The new species has a total of 17 cloacal papillae (four large and pedunculated pairs of precloacal papillae, an unpaired precloacal papilla and four pairs of postcloacal papillae). The arrangement of postcloacal papillae are as follows: the first pair are large, pedunculated and placed near the posterior edge of cloaca; the three remaining postcloacal pairs are grouped and located near the posterior tip. In the latter group, papillae in the first pair are large and pedunculated. Parasitized host and geographical distribution are also useful criteria to distinguish P. canariensis n. sp. from the remaining species of the genus Protospirura. In addition, the cytochrome c oxidase subunit 1 (cox1) sequence of the new species is provided and compared with available data of related species.

Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.

We propose a new binary formulation of the Travelling Salesman Problem (TSP), with which we overcame the best formulation of the Vehicle Routing Problem (VRP) in terms of the minimum number of necessary variables. Furthermore, we present a detailed study of the constraints used and compare our model (GPS) with other frequent formulations (MTZ and native formulation). Finally, we have carried out a coherence and efficiency check of the proposed formulation by running it on a quantum annealing computer, D-Wave\_2000Q6.

Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies were carried out, glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine, core- and/or an-tennary fucosylation. In the higher mass region these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as to understand pathogens molecular recognition.

The production and N-glycosylation of recombinant human butyrylcholinesterase (BChE), a model highly glycosylated therapeutic protein, in a transgenic rice cell suspension culture treated with kifunensine, a strong α-mannosidase I inhibitor, was studied in a 5 L bioreactor. A media exchange was performed at day 7 of cultivation by removing spent sugar rich media (NB+S) and adding fresh sugar free (NB-S) media to induce the rice α-amylase 3D (RAmy3D) promoter to produce rice recombinant human BChE (rrBChE). Using a 1.25X concentrated sugar-free medium together with an 80% reduced working volume during the media exchange lead to a total active rrBChE production level of 79 ± 2 µg (g FW)^-1 or 7.5 ± 0.4 mg L^-1 in the presence of kifunensine, which is 1.5-times higher than our previous bioreactor runs using normal sugar free medium with no kifunensine treatment. Importantly, the amount of secreted active rrBChE in culture medium was enhanced in the presence of kifunensine, comprising 44% of the total active rrBChE at day 5 post-induction. Coomassie stained SDS-PAGE gel and Western blot analyses reveal different electrophoretic migration of purified rrBChE bands with and without kifunensine treatment, which is attributed to different N-glycoforms. N-Glycosylation analysis shows substantial increase of oligomannose glycans (Man5/6/7/8) in rrBChE treated with kifunensine compared to controls. However, mass transfer limitation of kifunensine is likely the major reason for incomplete inhibition of α-mannosidase I in this bioreactor study.

Halophytic plants are, by definition, well adapted to saline soils. However, even halophytes can face nutritional imbalance and accumulation of high levels of compounds such as oxalic acid (OA), and nitrate (NO₃^¯). These compounds compromise the potential nutritional health benefits associated with salt tolerant plants such as Portulaca oleracea. Thus, preventing the accumulation of non-nutritional compounds will allow plants to be grown in saline conditions as crops. To this end, two ecotypes (ET and RN) of Portulaca oleracea plants were grown under growth room conditions with two levels of salinity (0, 50 mM NaCl) and three ratios of nitrate: ammonium (0:100%; 33:66%; 25:75% NO₃^¯:NH₄⁺). The results showed that both ecotypes exposed to elevated NO₃^¯, showed severe leaf chlorosis, high levels of OA, citric acid, and malic acid, while plants of ecotype ET exposed to elevated NH₄⁺ concentrations (33% and 75%) and 50 mM NaCl displayed a marked reduction in OA content, increased total chlorophyll and carotenoid contents, crude protein content, total fatty acid (TFA) and α-Linolenic acid (ALA) thus enhancing leaf quality. This opens the potential to grow high biomass, low OA P. oleracae crops. Lastly, our experiments suggest that ecotype ET copes with saline conditions and elevated NH₄⁺ through shifts in leaf metabolites.

This study aimed to investigate the airborne release of N-nitrosodimethylamine (NDMA) as a result of the dry heat cooking of some meats using charcoal grilling and pan broiling methods. Three types of meat, beef sirloin, pork belly, and duck, were chosen and cooked in a temporary building using the above methods. Air samples were collected in Thermosorb-N cartridges, which were qualitatively and quantitatively analyzed for NDMA using ultra-high performance liquid chromatography–mass spectrometry and high-performance liquid chromatography–fluorescence detection, respectively. Overall, the charcoal grilling method showed higher average NDMA concentrations than the pan broiling method for all types of meat. The highest average concentration was observed for charcoal-grilled beef sirloin (410 ng/m3) followed by pork belly, suggesting that meat protein content and cooking duration are important determinants of NDMA formation. Cancer risk assessment showed that the charcoal grilling of such meats can pose an additional cancer risk for restaurant customers.

Metal oxide p-n heterojunction nanofibers (NFs) are among the most promising approaches to enhancing the efficiency of gas sensors. In this paper, we report the preparation of a series of p-NiO-loaded n-ZnO NFs, namely (1 − x) ZnO-xNiO (x = 0.03, 0.05, and 0.1 wt%), for hydrogen gas sensing experiments. Samples were prepared through the electrospinning technique followed by a calcination process. The sensing experiments showed that the sample with 0.05 wt% NiO loading resulted in the highest sensing performance at an optimal sensing temperature of 200 °C. The sensing mechanism is discussed in detail and contributions of the p-n heterojunctions, metallization of ZnO and catalytic effect of NiO on the sensing enhancements of an optimized gas sensor are analyzed. This study demonstrates the possibility of fabricating high-performance H₂ sensors through the optimization of p-type metal oxide loading on the surfaces of n-type metal oxides.

Background and objectives: Contrast-induced nephropathy (CIN), is an acute renal damage due to contrast agents. This study is conducted to determine the potential diagnostic value of hypoxia-inducible factor 2-alpha (HIF2-α) and to evaluate the renal protective effects of N-acetyl cysteine (NAC) and sildenafil in a rat CIN model. Material/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Totally, rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN+NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modelling, prophylactic treatment was performed at 24th and 48th hours. After 48 hours of the modelling; blood, urine, tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum and urine samples. Renal sections were performed in order for histopathologic and immunohistochemical evaluations. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC, efficiently decreased the renal damage due to contrast agents (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study constructs an experimental base for the use of HIF-2α for clinical prevention and treatment of CIN. Several mechanisms may be postulated for the changes in HIF-2α levels. Besides, the increased HIF-2α levels with CIN and decreased HIF-2α levels after treatment may be used for the treatment and follow-up of patients with CIN.

Soil above a platinum-group element (PGE)-bearing horizon within the Freetown Layered Intrusion, Sierra Leone contains anomalous concentrations of n-alkanes (CnH2n+2) in the range C14 to C22 not readily attributable to an algal or lacustrine origin. Longer chain n-alkanes (C23 to C31) in the soil were derived from the breakdown of leaf litter beneath the closed canopy humid tropical forest. Spontaneous breakdown of the longer chain n-alkanes to form C14-22 n-alkanes without biogenic or abiogenic catalysts is unlikely as the n-alkanes are stable. In the Freetown soil, the catalytic properties of the PGE (Pt in particular) may lower the temperature at which oxidation of the longer chain n-alkanes can occur. Reaction between these n-alkanes and Pt species such as Pt2+(H2O)2(OH)2 and Pt4+(H2O)2(OH)4 can bend and twist the alkanes, and significantly lower the Heat of Formation. Acknowledging the possibility of microbial catalysis and the difficulty of identifying a direct organic geochemical source of the lighter n-alkanes, this paper explores the theoretical potential for abiogenic Pt species catalysis as a mechanism of breakdown of the longer n-alkanes to form C14-22 alkanes. This novel mechanism could substantiate the presence of the PGE in solution predicted by soil geochemistry and illustrate processes involving the PGE. Graphical Abstract

A New monogalactosyldiacylglycerol (MGDG), a known monogalactosylmonoacylglycerol (MGMG) and a known polyunsaturated fatty acid methyl ester (PUFAME) were isolated from the marine dinoflagellate Karenia mikimotoi. The planar structure of the glycolipids was elucidated using MS and NMR spectroscopic analyses and comparisons to the known glycolipid to confirm its structure. The isolation of PUFAME strongly supports the polyunsaturated fatty acid fragment of these glycolipids. The relative configuration of the sugar was deduced by comparisons of 3JHH values and proton chemical shifts with those of known glycolipids. All isolated compounds MGDG, MGMG and PUFAME (1-3) were evaluated for their antimicrobial and anti-inflammatory activity. All compounds modulated macrophage responses, with compound 3 exhibiting the greatest anti-inflammatory activity.

During the last two decades several cases of venous thrombosis (VTE) after a prolonged period at a computer has been described, denominated “eThrombosis”. Video gaming on a computer has become very popular and can be a social activity where several players are gathered to play against each other or in a virtual environment for several days (“LAN (i.e., Local Area Network) parties”) where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate a potential coagulation activation during a 42 hour LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 hours, and plasma was analyzed for thrombin generation, and Thrombin-antithrombin-complexes (TAT), prothrombin Fragment 1+2 (F1+2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h gaming with minimal physical activity. Although an increased activity cannot be excluded, it does not directly indicate a risk of VTE in general. It may be specific and particularly susceptible in-dividuals who are prone to thrombosis and, therefore, are at risk of developing e-thrombosis.

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.

D-Glucaric acid is an important bio-based building block of polymers and is a high value-added chemical that can be used in a variety of applications. In the present study, the Udh target genes from Pseudomonas putida and Pseudomonas syringae were used together to construct the expression vector pETDuet-2×Udh. The transformants of BL21(DE3) with vector pETDuet-2×Udh was applied to produce glucaric acid from glucuronic acid. After optimization of induction conditions, the highest Udh expression were achieved when 0.4 mmol L-1 isopropyl-β-d–thiogalactoside (IPTG) was added to cell cultures at an OD600 value of 0.6 followed by culture at 26℃ for 6 hours. The production of glucaric acid substantially reached 5.24 ± 0.015 g L-1 in fed-batch cultures in a 30 L tank. In the present study, a new system for glucaric acid production was established, which was more economic and friendly to environment.

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.

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

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.

Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin and MMP2, enhancing drug resistance and migration in recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights to the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.

The present study describes the preparation of a composite material consisting of thermoplastic polyurethane-poly (n-isopropylacrylamide) (TPU-PNIPAM), which was employed for the se-lective adsorption separation of alcohol/water mixed solutions for the first time. The findings revealed that TPU and PNIPAM were interconnected through interchain hydrogen bonding, resulting in exposed hydrophobic isopropyl groups while covering the hydrophilic hydrogen bond sites. Selective separation of alcohols from alcohol/water mixed solutions occurred via London dispersion forces between alkyl groups. Increasing the PNIPAM load on the TPU surface led to a decrease in available hydrogen bond sites capable of bonding with water molecules, an increase in dispersible isopropyl groups interacting with alcohol alkyl groups, and enhanced selective adsorption capacity of TPU-PNIPAM towards alcohol/water mixed solutions. Moreover, TPU-PNIPAM exhibited a characteristic fast-slow-fast-equilibrium ad-sorption curve for different initial concentrations of alcohol/water mixtures, and its selective adsorption capacity increased when temperature reached 55℃. In addition to these general trends, under identical conditions, the selective adsorption capacity of TPU-PNIPAM gradually increased by methanol < ethanol < isopropyl alcohol < propyl alcohol, thus indicating a positive correlation between selectivity performance and hydrophobicity level.

The field of fluorescence sensing, leveraging various supramolecular self-assembled architectures constructed from macrocyclic pillar[n]arenes, has seen significant advancement in recent decades. This review comprehensively discusses, for the first time, the recent innovations in the synthesis and self-assembly of pillar[n]arene-based supramolecular architectures (PSAs) containing metal coordination sites, along with their practical applications and prospects in fluorescence sensing. Integrating hydrophobic and electron-rich cavities of pillar[n]arenes into these supramolecular structures endow the entire system with self-assembly behavior and stimulus responsiveness. Employing the host–guest interaction strategy coupled with complementary coordination forces, PSAs exhibiting both intelligent and controllable properties are successfully constructed. This provides a broad horizon for advancing fluorescence sensors capable of detecting environmental pollutants. This review aims to establish a solid foundation for the future development of fluorescence sensing applications utilizing PSAs. Additionally, current challenges and future perspectives in this field are discussed.

In this paper the thermodynamic and reactivity study of light alcohol fuels was prepared, based on experimental and numerical results. We also tested the influence of water addition on fundamental properties of the combustion reactivity dynamics in closed vessels, like the maximum explosion pressure, maximum rate of pressure rise and the explosion delay time of alcohol-air mixtures. Substances that we investigated were: methanol, ethanol, n-propanol and iso-propanol. All experiments were conducted at initial conditions of 323.15 K and 1 bar in a 20 dm3 closed testing vessel. We investigated the reactivity and thermodynamic properties during the combustion of liquid fuel-air mixtures with equivalence ratios between 0.3-0.7 as well as some admixtures with water, to observe water mitigation effects. All light alcohols samples were prepared at the same initial conditions on a volumetric basis by mixing the pure components. The volumetric water content of the admixtures was varied from 10 to 60 vol%. The aim of water addition was to investigate the influence of thermodynamic properties of light alcohols and to find out to which extent a water addition may accomplish mitigation of combustion dynamics and thermodynamic reactivity.

A enantioselective tandem transformation concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs) in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

Abstract: Objective: The aim of this study is to evaluate the effectiveness of an affective-sexual education programme among 14-15 year-old adolescents and its impact on their perception of their health. Design: This is a quantitative, descriptive and prospective quasi-experimental study, employing various cross-sections throughout the school year. It constitutes an educational promotion intervention where a health blog serves as a supplementary component to the "Health and School" programme. This phase is assessed using specific tools designed to evaluate scales. The study aims to assess the programme's effectiveness in the areas of knowledge and attitudes related to sexuality, sexually transmitted diseases, and affectivity. Additionally, it aims to evaluate the intervention's impact on 292 secondary school students, divided into a control group (N=144) and an intervention group (N=148). Both groups belong to the same population and have undergone affective-sexual education interventions focusing on gender and sexual diversity perspectives. The assessment considers perceptions and behaviours related to knowledge about HIV and other STDs/STIs, attitudes towards HIV, health anxiety, and AIDS phobia. Cross-sectional comparisons between the control and intervention groups are conducted at three points during the school year: longitudinal study, baseline, at month 4, and at month 9 post-intervention. Methods: Median and interquartile range, Wilcoxon test for numerical variables and Fisher's test for categorical variables were calculated according to intervention group. Results: 53% of the students reported a very good perception of health, compared to 45% with a good perception. Boys reported a good perception of health (85%) and had perceptions of their physical appearance and health (p=0.023) and (p<0.001) in the intervention group. Differences were found between perceptions of physical appearance in the control group, which was close to normal (p=0.429). In terms of level of knowledge about HIV and other STDs/STIs, the most significant difference was found in knowledge about HIV transmission, which varied between groups. Conclusions: Early affective-sex education sessions have an impact on health perception and behaviours related to knowledge about HIV and other STDs/STIs, leading to reduced anxiety in adolescents. School nurses should focus on health promotion, prevention of sex-related diseases, healthy attitudes from a gender perspective and integrated affective relationships in all their dimensions.

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

Ransomware attacks have risen alarmingly, with encryption techniques becoming more complex. This paper introduces a novel detection model tailored for ransomware's distinctive characteristics. The Intel PIN tool extracts Windows API invocation sequences related to file operations. These sequences are used to construct n-grams, forming feature vectors enhanced by a new Class Feature Weighting (CFW) metric to improve malware detection. Preliminary results demonstrate elevated accuracy and precision versus existing methods. The major contributions are: (1) Introducing an innovative deep learning model for few-shot ransomware classification using entropy features and transfer learning. (2) Achieving high weighted F1-score in classifying ransomware variants into families with limited training data. (3) Demonstrating the potential of entropy-based features to capture intricacies lost in image-based approaches, improving detection of new strains.

Audio recording in classrooms is a common practice in educational research, with applications ranging from detecting classroom activities to analysing student behaviour. Previous research has employed neural networks for classroom activity detection and speaker role identification. However, these recordings are often affected by background noise that can hinder further analysis, and the literature has only sought to identify noise with general filters and not specifically designed for classrooms. Although the use of high-end microphones and environmental monitoring can mitigate this problem, these solutions can be costly and potentially disruptive to the natural classroom environment. In this context, we propose the development of a neural network model that can specifically detect and filter out background noise in classroom recordings. This model would allow the use of lower quality recordings without compromising analysis capability, thus facilitating data collection in natural educational environments and reducing the costs associated with high-end recording equipment.

Microwave absorbers with lightweight, good stability and high efficiency have attracted much attention for their applications in many contemporary fields. In this work, the 3D porous (Ni@NO-C)n/NO-C composite absorber was prepared by a wet chemistry method with Ni chains and melamine as precursors, in which NO-C (N,O-doped carbon) encapsulated Ni particles are homogenously dispersed in the 3D porous networks of NO-C in the form of (Ni@NO-C)n chains. The special microstructure of the as-prepared material is proved to be benefit for the improvement of its microwave adsorption performance. The as-synthesized (Ni@NO-C)n/NO-C composite ab-sorber exhibited an effective absorption bandwidth of 4.1 GHz and an extremely large reflection loss of -72.3 dB. The excellent microwave absorbing performances can be ascribed to the coopera-tive consequence of dielectric loss and magnetic loss along with the balance between attenuation capability and impedance match.

Bimetallic (or multimetallic) catalysis has emerged as a powerful tool in modern chemical synthesis, offering improved reaction control and versatility. This review focuses on the recent de-velopments in bimetallic sequential catalysis for the synthesis of nitrogen heterocycles, essential building blocks in pharmaceuticals and fine chemicals. The cooperative action of two (and sometimes more) different metal catalysts enables intricate control over reaction pathways, enhancing selectivity and efficiency of N-heterocyclic compounds synthesis. By activating less reactive substrates, this multimetal catalytic strategy opens new synthetic possibilities for challenging compounds. The use of catalytic materials in bimetallic systems reduces waste and improves atom efficiency, aligning with green chemistry principles. With a diverse range of metal combinations and reaction conditions, bimetallic catalysis provides access to a broad array of N-heterocyclic compounds with various functionalities. This paper highlights the significant progress made in the past decade in this topic, emphasizing the promising potential of bimetallic catalysis in drug discovery and the fine chemical industries.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

Soil nitrogen (N) is a common limiting factor where soil N cycling is a key component of agro-ecosystems. Soil N transformation processes are largely mediated by microbes and understanding bacteria involvement in soil N cycling in agricultural systems has both agronomic and environmental importance. This 2-yr field scale study examined the abundances and spatial distributions of total bacterial community (16s RNA), bacterial involved in nitrification (amoA), and de-nitrification (narG, nirK, and nosZ) and soil physicochemical properties of winter wheat (Triticum aestivum L.) – soybean (Glycene max L.) double cropping with 2-3 weeks of spring grazing (WGS) and without grazing (WS) and of tall fescue (Festuca arundinacea (L.) Schreb.) pasture (TF) managed to near natural conditions with similar grazing. The TF had a significantly higher abundance of 16S rRNA, amoA, narG, nirK, and nosZ genes than the WS and WGS, which had similar levels between themselves. Soil organic matter (OM) and soil pH had a stronger effect on the N-cycling bacteria gene abundance. All bacterial gene concentrations and soil pH showed non-random distribution patterns with 141-186 m range autocorrelation. These results indicate that biological N transformation processes are more important in natural agricultural systems and the abundance of N-cycling bacteria can be manipulated by field scale management strategies.

Differences in the physical and chemical properties of reclaimed water (RW) and natural surface water (SW) lead to the differences in terms of nitrogen and phosphorus release when pipeline sediments enter these water bodies. The nitrogen and phosphorus release kinetics from pipe sediments with different particle sizes have been investigated. The results demonstrated that both SW and RW had a pH buffering effect after sediment addition, and the final pH (approximately 8.1) of RW was lower. The release of total phosphorus (TP) and ammonia nitrogen ( NH₄⁺-N) fitted the first-order kinetic model where the release of TP reached equilibrium; TP release was inhibited in both SW and RW, where RW exhibited the lowest (by a factor of 1.23~2.44) release (0.002 mg/g). The release of NH4+-N was promoted in both SW and RW; the maximum release in RW was 0.0188 mg/g. The amounts of NH₄⁺-N released in SW and RW were 1.02-1.40 and 1.30-1.80 times that of the control group (CG), respectively. The percentage of TP and NH₄⁺-N release in the three groups was highest in 75-154 μm pipe sediment, reaching 34.53% and 43.51% in SW and RW, respectively. These results can assist in the development of water quality evolution models for specific urban scenarios, and provide important guidance for the precise regulation of recharge water quality during and after rainfall.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

In our tactic to construct bio-active molecules, a series of novel pyrimido[2,1-c][1,2,4]triazine-3,4-diones based heterocycles, were synthesized and evaluated for their in vitro antimicrobial impacts. The exploratory bioassay results declared that, the majority of the evaluated compounds exhibited considerable anti-microbial activity comparable to the reference drugs. Conjugates 15j, 15f, 15i, 15h, 15g and 15a were found to be the most potent antibacterial, indicating that conjugates bearing electron-attracting substituents exhibited higher potency than these with electron-releasing substituents.

This study investigated the removal characteristics of N-nitrosamines and their precursors at three pilot-scale water reclamation plants. These plants applies different integrated membrane systems: (1) microfiltration (MF) / nanofiltration (NF) / RO; (2) sand filtration/three-step RO; and (3) ultrafiltration (UF) / NF and UF / RO. Variable removal of N-nitrosodimethylamine (NDMA) by the RO membrane processes could be attributable to membrane fouling and feed water temperature. The effect of membrane fouling on N-nitrosamines removal was extensively evaluated at one of the plants by conducting one month of operation and chemical cleaning of the RO membrane element. Membrane fouling enhanced N-nitrosamines removal by the pilot-scale RO membrane process. This finding contributes to better understanding of variable removal of NDMA by RO membrane processes. This study also investigated the removal characteristics of N-nitrosamines precursors. The NF and RO membrane processes greatly reduced NDMA formation potential (FP), but the UF process had little effect. The contributions of MF, NF, and RO membrane processes for reducing FPs of NDMA, N-nitrosopyrrolidine (NPYR) and N-nitrosodiethylamine (NDEA) were different, suggesting different size distributions of their precursors.

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the Phosphatidylserine and the docking of 3 mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA-Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score, so mutations in this position were evaluated to observe the differences in intermolecular forces of the CagA-Phosphatidylserine complex. We evaluated the docking of 3 mutations: K636A, K636R and K636N. The models of the crystal and mutations presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG (χ²(1) = 93.82, p-value < 2.2 × 10⁻¹⁶) and the H-bonds (χ²(1) = 91.93, p-value < 2.2 × 10⁻¹⁶). In all the data, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA-Phosphatidylserine complex interaction.

We demonstrate for the first time efficient mechanical to electrical energy conversion using InGaN/GaN nanowires (NWs). Using an atomic force microscope equipped with a modified Resiscope module, we analyse the piezoelectric energy generation of GaN NWs and demonstrate an important enhancement when integrating in their volume a thick In-rich InGaN insertion. The piezoelectric response of InGaN/GaN NWs can be tuned as a function of the InGaN insertion thickness and position in the NW volume. The energy harvesting is favoured by the presence of a PtSi/GaN Schottky diode which allows to efficiently collect the piezo-charges generated by InGaN/GaN NWs. Average output voltages up to 330 ± 70 mV and a maximum value of 470 mV per NW has been measured for nanostructures integrating 70 nm-thick InGaN insertion capped with a thin GaN top layer. This latter value establishes an increase of about 35% of the piezo-conversion capacity in comparison with binary p-doped GaN NWs. By considering these output signals, we estimate a maximum power density generated by one layer of dense InGaN/GaN-based NW of about 3.3 W/cm². These results settle the new state-of-the-art for piezo-generation from GaN-based NWs and offer a promising perspective for extending the performances of the piezoelectric sources.

Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

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

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

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.