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

Two ligands, 1, 3-bis(4-carboxyphenyl)imidazolium chloride and 4, 4՛-bipyridine, were employed to prepare nickel and zinc azolium based MOFs, 1 and 2 by the mixed ligand solvothermal approach. The positively charged azolium moieties in the imidazolium linker resulted in a charged environment in the as-synthesized frameworks. As a result, 1 and 2 demonstrated preferential adsorption of CO2 over methane molecules in the gas phase adsorption due to the higher quadruple moment of CO2, which interacts more with the positively charged frameworks. Besides, in aqueous media, 1 and 2 exhibited incredible adsorption efficiency for anionic dyes. In the following, MOF 1 was metallated at the carbene site of the azolium linker to generate the novel heterogeneous catalyst 1-Pd, which was successfully applied for Sonogashira and Suzuki-Miyaura coupling reactions without losing its activity after three cycles.

The reactions of the angular ligand 4,4’-oxybis(N-(pyridin-3-yl)benzamide (L1) and 1,4-naphthalenedicarboxylic acid (1,4-H2NDC) with divalent metal salts yielded three distinct coordination polymers (CPs): {[Zn2(L1)(1,4-NDC)2]MeOH}n, 1, {[Cu(L1)(1,4-NDC)(H2O)]3H2O}n, 2, and {[Cd(L1)(1,4-NDC)]2H2O}n, 3. Complex 1 features a 2-fold interpenetrated 3D framework with the (412.63)-pcu topology, while complex 2 reveals a 1D triple-strained helical chain, and complex 3 displays a 3-fold interpenetrated 3D framework with (66)-dia topology. Additionally, the reactions of the flexible ligand N‚N’-bis(3-methylpyridyl)adipoamide (L2) afforded {[Co4(L2)0.5(1,4-NDC)3(H2O)3(µ3-OH)2]·EtOH·2H2O}n, 4, {[Zn2(L2)(1,4-NDC)2]·2CH3OH}n, 5, and [Cd(L2)(adipic)(H2O)]n (H2adipic = adipic acid), 6, exhibiting a self-catenated 3D framework with the (420.68)-8T32 topology, a 2D layer with the (413·62)-(4,4)IIb topology, and a 2D layer with the (44·62)-sql topology, respectively. The structural diversity observed in complexes 1 - 6 highlights the pivotal influence of the metal center on the degree of entanglement in CPs within mixed-ligand systems. The thermal stability and luminescent properties of complexes 1 - 3, 4, and 6 are also discussed.

Aiming at the limitations of single-functionality, limited applicability, and complex designs prevalent in current metasurfaces, we propose a terahertz multifunctional and multiband tunable metasurface utilizing a VO2-metal hybrid structure. This metasurface structure comprises a top VO2-metal resonance layer, a middle polyimide dielectric layer, and a gold film reflective layer at the bottom. This metasurface exhibits multifunctionality, operating independently of polarization and incident angle. The varying conductivity states of the VO2 layers, enable the metasurface to achieve various terahertz functionalities, including single-band absorption, broadband THz absorption, and multiband perfect polarization conversion for linear (LP) and circularly polarized (CP) incident waves. Finally, we believe that the functional adaptability of the proposed metasurface expands the repertoire of options available for future terahertz device designs.

[Co(AMPY)(DAPY)Cl2(H2O)].H2O (1) [Cu(AMPY)(DAPY)Cl2(H2O)].H2O (2) [Zn(AMPY)(DAPY)Cl2(H2O)] (3) were prepared from the ligands; AMPY = 2-amino-4-methylpyrimidine (L1), DAPY = 2,3-diaminopyridine (L2) and CoCl2.6H2O, CuCl2.2H2O and ZnCl2 in water/ethanol solutions and the three products characterized by elemental analysis, ultraviolet-visible spectroscopy (UV–Vis), Fourier-transform infrared spectroscopy (FT-IR), magnetic susceptibility, molar conductivity methods, and TGA analysis. The X-ray powder diffraction of the Co(II), Cu(II), and Zn(II) compounds showed that the geometry of monoclinic and SEM analysis revealed their morphology with a smooth surface. Molecular modeling was performed for all compounds using the density functional method DFT/B3LYP to study the structures and the frontier molecular orbitals (HOMO and LUMO). We have used Gaussian09 software for the calculations. In this study, different complexes were tested against Gram negative and Gram positive bacterial species to give insight into their broad-spectrum effects. The used pathogenic strains were two Gram positive species "Staphylococcus aureus and Micrococcus luteus" and two Gram negative species "Salmonella thyphimurium and Escherichia coli. The antifungal activity was evaluated against a pathogenic reference strain of the yeast Candida albicans. The antimicrobial and antioxidant assay results demonstrate that the tested compounds are effective against Gram positive and negative bacteria. Additionally, the compounds have an antifungal effect against Candida albicans with a maximum inhibitory zone of 2.5cm. The results demonstrated high antioxidant potential for the Zn(II) complex with a DPPH scavenging of 91.5%, however, the Cu(II) complex was low (16.5%). The data of docking with tyrosyl-tRNA synthetase presented that all compounds fit very well in the catalytic pockets of the proteins of the receptor.

Objetives/Background: Vitamin D Binding Protein (VDBP) and free vitamin D are new markers that are being studied as a possible markers of vitamin D status. The main aim of our study was to analyse the VDBP genotype and quantify the levels of VDBP and free vitamin D in a sample of cystic fibrosis (CF) patients. Methods: Multicentre, cross-sectional and prospective study including patients with CF, exocrine pancreatic insufficiency who were clinically stable. We investigated vitamin D levels (total and free) and the different VDBP haplotypes. Free vitamin D levels were measured using an electro-chemiluminescence assay. Results: A sample of 48 patients was obtained (52% male; median age 13.8 years). The most common allele of VDBP was Gc1s (72%)>Gc2 (52%)>Gc1f (27%). Median calcidiol was 21.2 ng/ml (IR 15.3 - 26.9), 81% had levels in the insufficiency range: 23 patients (48%) below 20 ng/ml, and 16 (33%) between 20 and 30 ng/ml. The median free vitamin D level was 4.2 pg/ml (IR 3.9 – 5.6). A positive correlation was observed between calcidiol and free vitamin D levels (r=0.871; p<0.0001). After adjustment for season, vitamin D supplementation, sex and CFrelated diabetes, patients with Gc1f polymorphism had a lower risk of vitamin D deficiency, OR 0.22 (95% CI 0.05 – 0.99), p=0.027. A negative linear trend was observed between the polymorphisms grouped into 3 categories (Gc1/Gc1, Gc1/Gc2, and Gc2/Gc2, in that order) and vitamin D and free vitamin D levels (p=0.025 and p=0.033, respectively). Conclusion: In CF, as in the general population, the most common VDBP haplotype in Caucasian race is Gc1s. VDBP polymorphisms influence serum vitamin D and free vitamin D levels in CF patients. There is a good correlation between free vitamin D and calcidiol levels, suggesting that measuring the latter in CF does not seem to provide any additional benefit.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR–pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR–pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor–ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model’s accuracy and robustness across multiple TCR–pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation.

Antimicrobial resistance is an increasing problem for the global public health. One of the strategies to combat this issue is the synthesis of novel antimicrobials through rational drug design based on extensive structure-activity relationship studies. The thiazole nucleus is a prominent feature in the structure of many authorized antimicrobials, being clubbed with different heterocycles. The purpose of this review is to study the structure-activity relationship in antimicrobial thiazoles clubbed with various heterocycles reported in the literature between 2017 and 2022, in order to offer an overview of the last years in terms of antimicrobial research and provide a helpful instrument for future research in the field.

We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

The purpose of our work was the search for safe and effective biologically active substances of cardiotropic action among 1,3- thiazole derivatives. New derivatives of 1-[(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-yl]ethan-1-one and ethyl-(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-carboxylate were synthesized by the Hantzsch reaction. The structure of the compounds obtained was confirmed by ¹H NMR spectroscopy and by the elemental analysis. The pharmacological screening showed that the obtained substances possess cardiotropic activity. The cardiotropic properties of the new 1,3-thiazole derivatives were studied on the isolated rings of the thoracic aorta of laboratory rats. A prospective substance 1-[(2Z)-2-[(4-methoxyphenyl)imin]-4-methyl-3-(4-methylpiperazin-1-yl) -2,3-dihydro-1,3-thiazol-5-yl]ethan-1-one hydrochloride, which exhibits cardiotropic activity exceeding the activity of L-carnitine and meldonia has been revealed during pharmacological researches of the substances obtained.

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

The synthesis of enantiomeric forms of D-amino acids can be achieved by a two-step "hydantoinase process" based on the sequential catalysis of substrates by specific enzymes, D-carbamoylase and D-hydantoinase. In addition to our previously studied D-hydantoinase, we describe here the structural features of D-carbamoylase from Pseudomonas, the encoded gene of which was chemically synthesized and cloned into Escherichia coli. A significant fraction of the overexpressed recombinant protein forms insoluble inclusion bodies, which are partially converted to a soluble state upon treatment with N-lauroylsarcosine or upon incubation of the cells at low temperatures. Analysis of the substrate specificity of the purified His-tag protein showed that D-carbamoylase exhibits the highest activity toward N-carbamoyl-D-alanine and N-carbamoyl-D-tryptophan. Molecular docking analysis revealed the location of the substrate binding site in the three-dimensional structure of D-carbamoylase. Molecular dynamics simulations showed that the binding pocket of the enzyme in complex with N-carbamoyl-D-tryptophan is stabilized within 100 ns. The free energy of binding indicated a possible role of residues Arg176 and Asn173 in the formation of hydrogen bonds between the enzyme and N-carbamoyl-D-tryptophan. The properties of the studied D-carbamoylase and D-hydantoinase support further development of a combined biotechnological process for the production of new drugs and peptide hormones.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Brand trust holds significant importance in the Mongolian cashmere industry. This study examines the primary predictors of customer brand trust among Mongolian cashmere users. Our research includes a survey with 800 participants and 20 individual interviews conducted among both Mongolian cashmere users and non-users. We utilized an online platform to reach participants, employing convenience sampling. The study investigates the relationship between various factors and brand trust within the context of Mongolian cashmere brands. Through a combination of in-dividual interviews and statistical analysis, we test six hypotheses. The findings indicate that higher brand quality, a strong reputation, greater transparency, effective issue resolution, commitment to environmental and social responsibility, and pre-purchase research on such commitments positively impact brand trust. Key insights gleaned from the interviews emphasize the importance of quality, reputation, transparency, customer service, and environmental responsibility in shaping consumer trust. These results offer valuable implications for cashmere brands aiming to bolster consumer trust and foster loyalty.

The adversarial vulnerability of deep learning models is a critical issue that must be addressed to ensure the safe commercialization of AI technologies. Although numerous studies on adversarial defense methods are actively being conducted from various perspectives, most of them still provide limited robustness, and even the relatively trusted adversarial training is no exception. To develop more reliable defense methods, ongoing research exploring the properties and causes of adversarial vulnerabilities is essential. In this study, we focus on a hypothesis regarding the existence of adversarial examples: The adversarial examples represent low-probability “pockets” in the manifold. Assuming that the hypothesis holds true, we propose a method for generating perturbation: “mixed perturbation (MP)”, which aims at discovering diverse pocket samples in a defensive perspective. The proposed method generates perturbations by leveraging information from both the main task and auxiliary tasks in multi-task learning scenarios, combining them through random weighted summation. The generated mixed perturbation intends to maintain the primary directionality of the main task perturbation to improve the model’s main task recognition performance while introducing variability in the perturbation directions. We then utilize them for adversarial training to form more robust decision boundary. Through experiments and analyses conducted on five benchmark datasets, we validated the effectiveness of our proposed method.

To address the problems of insufficient semantic fusion between text and questions and the lack of consideration of global semantic information encountered in machine reading comprehension models, we proposed a machine reading comprehension model called BERT_hybrid based on BERT and hybrid attention mechanism. In this model, BERT is utilized to separately map the text and questions into the feature space. Through the integration of Bi-LSTM, attention mechanism, and self-attention mechanism, the proposed model achieves comprehensive semantic fusion between text and questions. The probabilities distribution of answers is computed using Softmax. Experimental results on the public dataset DuReader demonstrate that the proposed model achieves improvements in BLEU-4 and ROUGE-L scores compared to existing models. Furthermore, to validate the effectiveness of the proposed model design, we analyze the factors influencing the model’s performance.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

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

Vitamin D receptor (VDR) is an important candidate gene in musculoskeletal phenotypes. Polymorphisms in VDR have been previously associated with several pathologies and muscular strength in athletes and elderly people, however literature reported contradictory results. The object of this research is to verify the association between the most studied VDR variants (rs2228570, rs7975232, and rs1544410) and the increase of muscle mass in elite young soccer players. A sample of 55 soccer players (15-18 years old) form a professional team was selected for this study. DNA was extracted by salting out method and polymorphisms were genotyped by PCR-RFLP, followed by 2% agarose gel electrophoresis. To test the effect of the three SNPs, logistic regression analysis was applied. Body composition was carried out through skinfold thickness method, and muscular area of arm and lower limb were calculated using Frisancho formulas. All three polymorphisms met Hardy-Weinberg equilibrium (p &gt; 0.05) and their frequencies fell within the worldwide variability. A significant correlation between rs1544410 and increase of calf muscle mass was observed. Individuals carrying A allele showed higher calf muscular mass than those carrying the G allele (p = 0.034). Moreover, haplotype analysis applied to the two SNPs in linkage disequilibrium (rs7975232 and rs1544410), showed that AG haplotype resulted negatively correlated to calf muscle area. In conclusion, we confirm an association between VDR polymorphisms and muscular mass that could encourage the genetic screening of VDR gene to identify a potential risk of injury and for individual nutritional interventions.

Vitamin D and iron deficiencies are the most prevalent micronutrient deficiencies among women of reproductive age (WRA) in Morocco. Recent studies suggest that Vitamin D deficiency (VDD) may reduce iron bioavailability necessary for erythropoiesis, potentially leading to iron deficiency (ID) and anemia. This study investigates the association between vitamin D status, iron levels, and anemia risk among Moroccan WRA aged 18-49 years. A cross-sectional study was conducted with 463 participants. Serum levels of 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine were measured. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were evaluated using validated questionnaires, and anthropometric data were collected. Linear and logistic regression models assessed the relationships between variables, while Receiver Operating Characteristic (ROC) curve analysis evaluated the predictive accuracy of VDD for ID and anemia. VDD (25(OH)D &lt; 20 ng/ml) was significantly associated with lower levels of hemoglobin, hematocrit, red blood cells, and ferritin (all p &lt; 0.01), suggesting a role of vitamin D in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19-19.28, p &lt; 0.001), ID (OR: 2.20, 95% CI: 1.32-3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73-12.08, p = 0.004). Dietary iron intake was inadequate among all participants, with minimal protective effect against anemia and ID (β(SE): -0.08(0.03), p = 0.030 and β(SE): -0.05(0.02), p=0.037 respectively). ROC analysis demonstrated moderate discriminative power for VDD in diagnosing IDA and anemia (AUC: 0.643 and 0.603) but reduced accuracy for ID (AUC: 0.575). This study identifies VDD as a significant risk factor for impaired iron status and anemia among Moroccan WRA, underscoring the need for targeted nutritional interventions and further research to explore effective prevention strategies.

Partially state-owned firms are common in both developed and developing countries and contribute around 10% of the world's GDP. This has led to a rich literature exploring various aspects of competition between such “mixed”-ownership firms. This paper contributes to the existing literature by studying the effects of mixed ownership on the intensity of competition in oligopoly markets. Our findings indicate that state ownership exerts an anti-competitive influence, with a higher state ownership share resulting in less aggressive behavior by firms in the product market. This result implies that industries with a higher proportion of state ownership yield lower total surplus. Further, when considering factors such as taxes, soft budget constraints, and weak property rights, the anti-competitive effects of state ownership are accentuated.

The construction of artificial grasslands using native species is an effective measure to restore degraded grassland. In this study, three native grass species, Elymus nutans, Elymus tangutorum and Poa litwinowiana, domesticated in the northern Tibetan Plateau, were used as test subjects. Three monocultures El. N, El. T and Po. L and four mixed combinations El. N+El. T, El. N+Po. L, El. T+Po. L and El. N + El. T + Po. L were set up, with 7 sowing combinations as the main zones, and nested fertilization and non-fertilization as the secondary zones. The optimal sowing combinations were selected to clarify the community growth dynamics of different grass pasture, and to investigate the transgressive overyielding and diversity effects of artificial grassland and the response of soil chemometrics to fertilizer application, with a view to providing a scientific basis for ecological restoration of degraded grassland in the northern Tibetan Plateau. The results show that the different sowing combinations of grassland all exhibit significant growth, with aboveground biomass peaking on 20 September. The type of El. N is the dominant community of the mixed combinations. The forage yield was highest in the combination, and the fertilization treatment significantly increased the forage yield. El. N + El. T + Po. L mixed sowing with fertilizer application is the recommended methodology to establish artificial grassland in the northern Tibetan Plateau. The relative yield totals of the mixed combinations were all greater than 1, and all were transgressive overyielding. Combined with the analysis of the distribution of soil ecological stoichiometric characteristics under fertilizer and non-fertilizer treatments, it was found that aboveground biomass and transgressive overyielding coefficients responded to soil ecological stoichiometry in completely different ways. Under the unfertilized treatment, soil C, N and P are regulated primarily through microbial stoichiometry under the resource dependence of soil dissolved nutrient stoichiometry, which affected aboveground of artificial grassland. Under the fertilizer treatment, microbially mediated extracellular enzyme stoichiometry was dynamically changing to regulate the new substrate environmental supply and demand balance derived from fertilizer application. Future research should further explore the long-term effects of these combinations under different environmental conditions and integrate other ecological restoration techniques to enhance the sustainability and ecological benefits of artificial grasslands. This will help achieve ecological balance and efficient utilization of forage resources in the Tibetan Plateau region, providing a more comprehensive scientific basis for regional environmental protection.

Frequently Asked Questions (FAQs) systems rely on semantic symmetry similarity measuring between two sentences. To address the challenges of insufficient training data and limited domain-specific understanding in low-resource FAQs, this paper proposes a general framework, PDAMF-FAQ, to solve these issues. Firstly, we propose a paraphrasing-based data augmentation model that integrates syntactic information and edit vectors. Using a rule-based approach, it retrieves template sentences from a corpus and masks relevant words with special characters. Edit vectors between the original and paraphrase sentences are added to a pre-trained model's encoding layer to enhance the model's ability to learn the differences between the original and reference paraphrase sentences. Additionally, this paper presents a mixed-feature semantic matching model based on SimBERT. The model extracts keyword features from the text, replacing these keywords with special characters to construct intent features. These intent features, along with the user question and keyword features, are then concatenated to form the model's input. Experiments were conducted respectively on the paraphrasing-based data augmentation model, mixed-feature semantic matching model and their comprehensive application in a low-resource domain-specific FAQ. The experimental results show that the proposed framework effectively improve the performance of domain-specific FAQ system.

The wellness economy has developed rapidly recently, particularly in wellness tourism. Wellness tourism transforms sustainable strategy through the availability of extended multi-actor engagement in service innovation to further the tourism experience. Therefore, when operating a wellness tourism destination, it is necessary to encourage multi-actor engagement in service innovation to achieve sustainable development. This paper introduces a mixed research method with the SWOT-AHP-QSPM, as it qualitatively analyzes the advantages, disadvantages, opportunities, and threats, constructs an evaluation index system, conducts quantitative analysis using the analytic hierarchy process, determines the index weight and weighted score, and calculate the sustainable development strategy, which is appropriate for wellness development of Chongqing Tea Mountain and Bamboo Forest National Forest Park. Purposive field surveys and personal interviews were conducted in Chongqing forest tourism destinations, involving 356 effective respondents. The research reveals that multi-actor engagement significantly enhances sustainable development. These findings bridge service innovation knowledge gaps and provide valuable insights for forest tourism destination management and sustainable policy strategies to elevate multi-actor engagement in forest sites.

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards, and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit set and yield in tree fruit production systems. Here we describe the metagenomics-based detection of plant viruses through bee and pollen samples collected during the spring bloom period from a mixed Prunus and Malus orchard. Twenty-one unique viruses were detected in samples collected during apricot (Prunus armeniaca), sweet cherry (Prunus avium), peach (Prunus persica), and apple blooms. Ilarviruses prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV), Secoviridae family members tomato necrotic ringspot virus, tobacco necrotic ringspot virus, and prunus virus F, and Capillovirus cherry virus A (CVA) were detected in all time points, while other viruses were detected with restricted ranges. These results demonstrate the benefits of area-wide monitoring through bee pollination activities, and provide new insights into the diversity of viruses in tree fruit pollination ecosystems.

:. Background and Objectives: Pulmonary embolism, PE, incidence had been increasing in the last ten years. Computed thoracic pulmonary angiography, CTPA, had a major role in confirming PE di-agnosis.The main purpose of the study was to establish the prognostic value of a CTPA parameter: pulmonary artery obstruction index, PAOI, for PE risk assessment . A second objective of the re-search was to investigate the predictive accuracy of biomarkers (D-dimer, and cardiac Troponin T, c-TnT ), and PAOI, in 7-day mortality. The third objective of the study was the relationship between PAOI, and these biomarkers, in different etiologies of PE. Materials and Methods: The study com-prised 109 patients with PE, hospitalized, and treated between February 2021, and August 2022. They had different etiologies: deep vein thrombosis, DVT; persistent atrial fibrillation, AF; chronic obstructive pulmonary disease, COPD, exacerbation; Covid; and cancers. The investigations were the following: clinical examination; D-dimer testing, as a mandatory method for PE suspicion( values ≥ 500 µg/L were highly suggestive for PE); c-TnT , as a marker of myocardial injury(values ≥ 14 ng/L were abnormal); CTPA, with right ventricle dysfunction, RVD, signs, and PAOI. Treat-ments were according to PE risk: systemic thrombolysis (in high risk , and hemodynamic instability); low weight molecular heparins, LWMH, after systemic thrombolysis, or in high risk PE, with he-modynamic stability; direct oral anticoagulants, DOAC (in low, and intermediate risk). Results: The relationship PAOI- D-dimer, and PAOI- c-TnT, had very strong statistical correlation, for the entire sample, and for DVT, AF, COPD, Covid subgroups ( Rho = 0.815-0.982). PAOI had a high predic-tive accuracy for intermediate , and high risk together (area under curve, AUC=0.948), and high risk PE (AUC= 0.993). For 7-day mortality, D-dimer , and c-TnT had high predictive accura-cy(AUC=0.921, and 0.979). PAOI had statistical significance for 7-day mortality in Covid (p=0.045), and cancer (p=0.038) patients. Conclusions: PAOI was an important tool for PE risk as-sessment. D-dimer , and c-TnT were valuable predictors, for 7-day mortality in PE. PAOI, and D-dimer; PAOI, and c-TnT were strongly correlated, for the entire PE sample, and for DVT, AF, COPD, and Covid patients.

The resilience of towns and cities refers to their ability to adapt and recover when confronted with pressures or challenges. This study employs ten variables as indicators to assess the resilience of urban areas by analyzing official data and constructing a multilevel mixed-effects structural equation model. The empirical findings demonstrate that enhancing resilience significantly influ-ences urban service functions, such as strengthening healthcare systems, stabilizing the real estate market, and addressing socio-economic challenges. Specifically, factors such as healthcare re-sources, housing demand, population structure, and social security exhibit varying levels of resil-ience, which profoundly impact the spatial distribution of these factors and socio-economic de-velopment. Disparities in healthcare resource allocation, demographic aging trends, and shifts in the housing market closely correlate with resilience levels in different regions. Additionally, the study emphasizes that improving resilience not only boosts the reliability and security of urban services but also ensures that communities receive necessary support and protection during times of adversity. Consequently, policymakers should recognize the pivotal role of urban resilience in resource allocation and social equity, devising corresponding strategies to enhance the resilience of these areas.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Listeria monocytogenes is an emerging pathogen responsible for the serious foodborne disease, listeriosis. The commensal gut microbiota is the first line of defense against pathogen internalization. The gut microbiome can be modified by prebiotic substrates, which are frequently added to food products and dietary supplements. Prebiotics should selectively support the growth of beneficial microbes and thus improve host health. Nevertheless, little is known about their effect on the growth of L. monocytogenes. The aim of this study was to evaluate the growth ability of four L. monocytogenes strains, representing the most common serotypes, on prebiotic oligosaccharides (beta-(1,3)-D-glucan, inulin, fructooligosaccharides, galactooligosaccharides, lactulose, raffinose, stachyose, and 2´-fucosyllactose and a mixture of human milk oligosaccharides) as a sole carbon source. The results showed that only beta-(1,3)-D-glucan was metabolized by L. monocytogenes. Therefore, the safety of beta-(1,3)-D-glucan with respect to listeriosis development should be further studied.

Idiopathic pulmonary fibrosis remains a relevant problem in the field of healthcare with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the reactions damaging the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and Nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of application of other approaches aimed at regulating the immune response, cellular aging processes, programmed cell death and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential application points and effects of vitamin D and its metabolites.

Background: This study introduces a novel dexamethasone (DEX) mixed micellar system (DEX-MM) using Soluplus® and Pluronic F-127 (PF127) to enhance ocular drug delivery. The enhancement of ocular application properties was achieved by creating a chitosan-coated DEX-MM (DEX-CMM), which promotes better adherence to the ocular surface, thereby improving drug absorption; Methods: Using the solvent evaporation method, a formulation was developed with a Soluplus® to drug ratio of 1:10, enhanced with 0.25% PF127. After dispersing in water, 1% chitosan (CS) was added. The stability and integrity of DEX within the micelles were verified using attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Additionally, in vitro and ex vivo drug release studies were con-ducted; Results: DEX-CMM (F6) demonstrated a particle size of 151.9±1 nm and a polydispersity index (PDI) of 0.168±0.003, suggesting uniformity and high electrostatic stability with a zeta po-tential of +35.96±2.13 mV. The non-Fickian drug release mechanism indicated prolonged drug retention. Comparative analyses showed DEX-CMM outperforming a standard DEX suspension in drug release and ocular tissue permeation, with flux measurements significantly higher than the DEX suspension; Conclusion: The study confirmed the efficacy of DEX-CMM in enhancing drug delivery to ocular tissues, evidenced by improved permeability. Safety evaluations using the HET-CAM test demonstrated that DEX-CMM was non-irritant, supporting its potential for effective ocular drug delivery.

Vitamin D plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother-placenta-fetus system. Low quantity of Vitamin D during pregnancy can lead to the elevated risk for preeclampsia occurence. Despite the numerous studies on the association of Vitamin D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review we summarize and analyze study data on the effects of vitamin D deficiency and supplementation on pregnancy, labor, fetal and neonatal outcomes.

Microplastics (MPs) are plastic particles ranging from 1,000 to 5,000 µm in diameter, posing a growing environmental and health risk. Composting is an excellent way to add nutrient-rich humus to the soil to boost plant development, but it also pollutes agricultural soil with MPs. Previous research has shown that MPs can threaten plant development, production, and quality, hence they must be studied. This study examined how a mixture of three MP types—polyethylene (PE), polystyrene (PS), and polypropylene (PP)—affected greenhouse tomato plant development. MP types were spiked at 1% w/w (MPs/soil) in tomato pots, whereas non-spiked growth medium was the control. Statistical analysis was conducted using an analysis of variance (ANOVA) and Tukey test (95% confidence) to compare treatments and controls. Soil spiked with MPs increased chlorophyll content (SPAD), transpiration rate, photosynthetic rate, and stomata conductance by 5.16%, 16.71%, 25.81%, and 20.75%, respectively, compared to the control but decreased sub-stomata CO2 concentration by 3.23%. However, MPs did not significantly affect tomato plant morpho-physiological features (p > 0.05). Biochemical analysis of tomato fruits showed significant (p < 0.05) reduction effects of MPs on carotenoid, total flavonoid, and sugar but increased protein, ascorbate, and peroxidase activity. However, there was no significant difference (p > 0.05) in the effects of the combined MPs on total phenolic content. These data imply that whereas MPs did not influence tomato plant physiological and morphological properties, tomato fruit biochemistry was reduced. This raise concerns that an increase in MPs in soils may reduce antioxidant content and negatively affect human health contributing to a decrease in food security.

In the field of 2-D image processing and computer vision, accurately detecting and segmenting objects in scenarios where they overlap or are obscured remains a challenge. This difficulty is worse in the analysis of shoeprints used in forensic investigations because they are embedded in noisy environments such as the ground and can be indistinct. Traditional Convolutional Neural Networks (CNNs), despite their success in various image analysis tasks, struggle with accurately delineating overlapping objects due to the complexity of segmenting intertwined textures and boundaries against a background of noise. This study introduces employs the YOLO (You Only Look Once) model enhanced by edge detection and image segmentation techniques to improve the detection of overlapping shoeprints. By focusing on the critical boundary information between shoeprint textures and the ground, our method demonstrates improvements in sensitivity and precision, achieving confidence levels above 85% for minimally overlapped images and maintaining above 70% for extensively overlapped instances. Heatmaps of convolution layers were generated to show how the network converges towards successful detection using these enhancements. This research may provide a potential methodology for addressing the broader challenge of detecting multiple overlapping objects against noisy backgrounds.

Utilizing groundwater offers a promising solution to alleviate water stress in Ethiopia, providing a dependable and sustainable water source, particularly in regions with limited or unreliable surface water availability. However, effective decision-making regarding well drilling and placement is essential to maximize groundwater resource potential, enhancing agricultural productivity, reducing hunger, and bolstering food security in Ethiopia. This study concentrates on the development of two-stage stochastic mixed integer programming (SMIP) models to optimize well placement for sustainable agricultural irrigation, considering uncertain demand scenarios. Additionally, a deterministic mixed integer programming model is formulated for comparison with the two-stage SMIP. Experiments are conducted to explore various demand scenario distributions, revealing that the optimized total cost for the two-stage SMIP generally exceeds that of a deterministic setting, aligning with the two-stage SMIP's focus on long-term benefits. Moreover, slight differences are observed in well layouts under different assumption scenarios. The study also examines the impact of selected parameters, such as fixed construction costs, per-meter drilling costs, and demand scenarios. The out-of-sample performance shows that the stochastic model is more flexible and resilient, with 11% and 4% lower costs than deterministic cases 1 and 3, respectively. This flexibility provides a more robust long-term strategy for well placement and resource allocation in groundwater management.

Vitamin D deficiencies are very common in pregnant women, raising concerns about adverse health outcomes in children. This issue has hardly been studied in multiple pregnancies, the prevalence of which has been steadily increasing. Therefore, our study investigated the relationship between newborns’ anthropometric parameters and the concentration of 25(OH)D in maternal blood of women with twin pregnancies and umbilical cord blood. The study included 50 women who gave birth after the 36th week of twin gestation. 25(OH)D was determined in maternal blood collected during the antenatal period and in the umbilical cord blood of 100 newborns. Anthropometric parameters of the newborns (birth weight, length, head and chest circumference) were obtained from hospital records. Data on nutrition and lifestyle during pregnancy were collected from the patients during an interview conducted by a dietitian. No relationship between maternal and neonatal cord blood vitamin D concentrations and any of the anthropometric parameters of the newborns was found. However, only 6% of the mothers and 13% of the newborns had vitamin D deficiency (≤20 ng/mL). The type of pregnancy and maternal height were the main factors associated with neonatal size. Newborns from dichorionic pregnancies were on average 202 g heavier (p<0.001) and 1 cm longer (p=0.006) than newborns from monochorionic pregnancies. Newborns of mothers ≤ 160 cm in height had on average 206 g lower birth weight (p=0.006) and were 3.5 cm shorter (p=0.003) compared to newborns of taller mothers. Therefore, in our study, neonatal size of the twins was not related to the vitamin D status but to other factors such as the type of pregnancy and maternal height.

Phosphatidylserine (PS) has significant applications in various sectors, such as the medical and food industries. However, its production relies heavily on phospholipase D (PLD), a crucial tool that is hindered by issues like poor stability and irrecoverability. Immobilization presents itself as an effective solution to overcome these limitations. In this study, magnetic graphene oxide (MGO) modified with amino (-NH₂) were synthesized and utilized for PLD immobilization. The activity of the immobilized PLD (MGO-PLD) reached 3062 U/g_MGO, with a specific activity of 33.9 U/mg_PLD, virtually identical to that of the free PLD. MGO-PLD was utilized to synthesize PS efficiently in a biphasic system. Under optimal conditions, PS yield reached 18.66 g/L, with a conversion rate of 92.8% and a productivity of 3.11 g/L/h. Notably, MGO-PLD retained an impressive PS conversion rate of 77.4% even after seven repetitive usages. Moreover, MGO-PLD displayed enhanced thermal and pH resistance properties compared to free PLD, alongside an augmented storage stability. Post a 8-week preservation at 4°C, its residual activity was able to maintain at 76.3%. This study provides a sustainable and highly efficient pathway for biocatalytic synthesis of PS.

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19, that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical and laboratory characteristics between children diagnosed with MIS-C who were admitted to the PICU or did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Patient’s demographic, clinical and laboratory data, were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR:12.89, 95%CI: 1.35-123.41, p-value=0.03) and cardiological involvement (OR:34.55, 95%CI: 2.2-541.91, p-value=0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 hours from admission, D-dimer levels higher than 4μg/mL and decreased Left Ventricular Ejection Fraction were associated with an increased risk of PICU admission (OR:7.95, 95%CI:1.48-42.78, p-value=0.02 and OR=1.28, 95%CI:1.07-1.53, p-value=0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value=0.005) and were hospitalized for more days, than children in the pediatric wards (median length of stay (IQR): 20 (15,28) days vs. 8.5 (6, 14) days, p-value&lt;0.001). Conclusions: In the present study, cardiovascular, hepatic involvement and increased D-dimer levels in children with MIS-C were associated with admission to the PICU.

The risk classification of barrier lake is the key to conducting emergency treatment in a scientific manner. Such difficulties are faced as short time for risk evaluation, complex evaluation indicators, difficulty in obtaining information quickly and quantifying index weights. Based on this, this paper constructs a quantitative risk classification model for barrier lakes based on D-AHP. On the basis of studies on nearly 100 cases of barrier lakes, an 8-factor evaluation index system and quantitative classification are proposed. The methods of rapid calculation of reservoir capacity curve of barrier lake and intelligent identification of particles on the surface of barrier body were developed, which realized the rapid acquisition of 8-factor evaluation index information in emergency environment. The D-AHP method dealt with inconsistent weight assignment to evaluation factors by experts, which helped achieve weight quantification of 8 factors. The risk assessment on15 barrier lakes such as Tangjiashan barrier lake show that the conclusion drawn with risk classification method proposed in this paper is basically consistent with that of the traditional table-lookup method. However, the table-lookup method ignores cumulative loss’s impacts on the risk level of barrier lakes, and considers the extremely severe loss of barrier lakes as a sufficient condition for the evaluation level to be grade I, and thus a deviation in the evaluation. The risk classification method proposed in this paper is more reasonable and reliable.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

The progesterone receptor (PR) mediates progesterone regulation of female reproductive physiology, as well as gene transcription in non-reproductive tissues, such as brain, bone, lung and vasculature, in both women and men. An unusual property of progesterone is its high affinity for the mineralocorticoid receptor (MR), which regulates electrolyte transport in the kidney in humans and other terrestrial vertebrates. In humans, rats, alligators and frogs, progesterone antagonizes activation of the MR by aldosterone, the physiological mineralocorticoid in terrestrial vertebrates. In contrast, in elephant shark, ray-finned fishes and chickens, progesterone activates the MR. Interestingly, cartilaginous fishes and ray-finned fishes do not synthesize aldosterone, raising the question of which steroid(s) activate the MR in cartilaginous fishes and ray-finned fishes. The simpler synthesis of progesterone, compared to cortisol and other corticosteroids, makes progesterone a candidate physiological activator of the MR in elephant sharks and ray-finned fishes. Elephant shark and ray-finned fish MRs are expressed in diverse tissues, including heart, brain and lung, as well as, ovary and testis, two reproductive tissues that are targets for progesterone, which together suggests a multi-faceted physiological role for progesterone activation of the MR in elephant shark and ray-finned fish. The functional consequences of progesterone as an antagonist of some terrestrial vertebrate MRs and as an agonist of fish and chicken MRs are not fully understood. Indeed, little is known of physiological activities of progesterone via any vertebrate MR.

Thermodynamics of protein-ligand interactions seems to be associated to a narrow range of Gibbs Free Energy. As a consequence, a linear enthalpy-entropy relationship showing an apparent Enthalpy-Entropy compensation (EEC) is frequently observed associated to the study of protein-ligand interactions. This EEC affects negatively the design and discovery of new and more efficient drugs capable of binding protein-targets with a higher affinity. Originally attributed to experimental errors, compensation between H and TS values is a real observable fact, although its molecular origin has remained obscure and controversial. Herein we show the results of a data search of G values of 2558 protein-ligand interactions and 3025 “in vivo” ligand concentrations from the Protein Data Bank bind Database and the Metabolome Data Base (2020). These results, together with the mechano-statistical interpretation of the thermodynamic properties leads to the conclusion that the EEC has no basis in statistical thermodynamics. It can be plausibly explained as a consequence of the narrow range of G associated to protein-ligand interactions. The Gaussian distribution of the G values matches very well with that of ligands. These results suggest the hypothesis that the set of G values for the protein-ligand interactions is the result of the evolution of proteins. The conformation versatility of present proteins and the exchange of thousands (even millions) of minute amounts of energy with the environment may have functioned as a homeostatic mechanism to make G of proteins adaptive to changes in availability of ligands, and therefore achieve the maximum regulatory capacity of the protein function. Finally, a plausible strategy to avoid the EEC is suggested.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Thurstonian scaling, i.e., Thurstonian discriminal distance δ or d' can be used as a sensory measurement index to measure and monitor food sensory difference/similarity between test and control samples due to potential food contamination. It can be obtained from any one of the sensory discrimination methods. Thurstonian scaling is theoretically independent of methods or scales used for its estimation. This paper discusses statistical inference including estimations and tests of hypothesis for d'. Ten basic sensory discrimination methods including 6 forced-choice methods and 4 methods with response bias are used in this paper to estimate d' values and their variances. Statistical tests are conducted based on the estimated d' values and their variances. The statistical tests include difference testing and equivalence/similarity testing for individual d' values for test and control samples and for two or multiple d' values for test samples. Application and significance of Thurstonian scaling for sensory discrimination methods is discussed generally. R codes for estimations and tests for d' values are provided in the paper.

(1) Background: To investigate the effect of phosphohistone H3 (PHH3) and vitamin D receptor (VDR) in the risk assessment of endometriosis, in two cohorts of women with this pathology, those receiving hormonal treatment, and those without treatment; (2) Methods: In 60 cases of women with endometriosis, the paraffin-embedded endometriosis tissue samples, retrieved after surgery, were immunohistochemically (IHC) analyzed aiming to determine the expression status of PHH3 and VDR; (3) Results: The IHC positive index of PHH3 and VDR of these two groups were compared. PHH3 levels were positively correlated with vitamin D levels, both being increased in patients without treatment. Within the group without treatment, PHH3 and VDR expressions were positively associated; (4) Conclusions: IHC analysis of PHH3 and VDR can be used as an additional tool for risk stratification and prognostic assessment in patients with endometriosis.

In December 2019, the so-called “coronavirus disease 2019” (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a “cytokine storm”. This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of COVID-19 and multi-system inflammatory syndrome in children (MIS-C). The effect of the pandemic confinement on vitamin D status and the hypotheses proposed to explain the age-related difference in the severity of COVID-19 are discussed. The role of vitamin D as a critical regulator of both innate and adaptive immune responses and the COVID-19 cytokine storm are analyzed. Vitamin D and its links to both COVID-19 (low levels of vitamin D appear to worsen COVID-19 outcomes) and the cytokine storm (anti-inflammatory activity) are detailed. Finally, the efficacy of vitamin D supplementation in COVID-19 is evaluated, but the evidence supporting vitamin D supplementation as an adjuvant treatment for COVID-19 remains uncertain.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for the c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards the c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

In forests, the microbial populations living in the soil can directly affect the carbon decomposed by the surface plants, and promote carbon storage and stability. In this study, 3 plots of 25.82 m×25.82 m were set up in 5 stand types, respectively. Soil samples were collected from 0~20 cm, 20~40 cm and 40~60 cm layers. Soil microbial composition, organic carbon component, pH, water content, bulk density, nitrogen, phosphorus, potassium and other physicochemical indexes and correlations were determined, and the correlations between soil carbon components and soil microbial functional modules in different mixed modes were analyzed. The results showed that: (1) The SOC of the same soil layer varied significantly, which also showed significant differences on the composition of soil bacteria and fungal microbial communities. Moreover, the bacterial community was more sensitive to the vegetation change environment, and the fungal community structure was more resistant to the influence of soil environment changes. (2) Fun_mod 1,6 and Bac_mod 7 were the microbial functional modules that played a decisive role in the process of soil carbon pool change, and the diversity and composition of bacterial community had more positive effects on soil organic carbon than that of fungal community. (3) Linear fitting and RDA results showed that POC in soil had the strongest correlation with SOC content, indicating that soil microorganisms affected the storage and stability of soil carbon mainly by regulating the conversion of surface plants (carbon sources) into POC. The soil environment of different mixed modes has different effects on soil carbon accumulation. Soil microorganisms affect soil carbon storage and stability mainly by regulating the conversion of surface plants (carbon sources) into POC forms.

Background: Delis-Kaplan Executive Function System (D-KEFS) is a neuropsychological tool used in clinical practice to measure executive function in clinical and non-clinical populations, in individuals aged 8-89 years, and consists of nine subtests that can be administered either as a single system or separately. Aims: In the present study, were established norms for the Verbal Fluency Test as well as the Design Fluency Test of the D-KEFS in a Greek population aged 20 to 49 years, since there is no previous study conducted in Greece for these age clusters. Methods: The study sample consisted of 100 healthy adults (44.4% male and 55.6% female), aged 20 to 49 years (M=32.81 SD=11.04) with education from 12 to 18 years (M=14.73, SD= .91). First, Spearman and Pearson tests explored the associations of gender, age and education with D-KEFS subtests’ performance. Afterwards, we calculated normative data using raw scores and transformed to percentile scores. Results: The present study is the first attempt to calculate norms for the two fluency subtests of the D-KEFS in Greek adult population stratified by age and educational level. Conclusion: Future research will promote the use of D-KEFS, in order to introduce a widely used tool which measures all basic executive functions subtypes for Greek adult population. Given that the majority of neuropsychological tools are adapted for older adult population, the current study aims at filling the gap in neuropsychological assessment of young adults as well as those who have co existing neurological or psychiatric disorders.

(1) Background: Many malignancies are driven by mutations which affect the gene for fibroblast growth factor receptor (FGFR) 1. Previously we have documented that signal transduction from FOP2–FGFR1 fusion protein in KG1 cells downregulated the expression of vitamin D receptor (VDR) gene. In this paper we investigated if also other FGFRs were responsible for the regulation of the VDR expression. (2) Methods: We used human myeloid leukemia cells U937, and bone cancer cell line U2OS, and cell transfection methods in order to address the above questions. (3) Results: In myeloid leukemia cells overexpression of FGFR 1-4 caused shift to granulocytic differentiation, upregulated expression of VDR, and sensitized these cells to 1,25-dihydroxyvitamin D (1,25D)-induced monocytic differentiation, while in bone cells, signal transduction activated by FGF1 was not responsible for regulation of VDR expression and activity. (4) Conclusions: Since the overexpression of FGFRs occurs in many neoplasms, it may be reasonable to use 1,25D analogs in these cancers, in which overexpression of FGFRs leads to VDR upregulation.

Breast cancer (BC) is the most common invasive neoplasm and affects many women of working age. The return to work (RTW) of female survivors (BCSs) is associated with a better quality of life and longer survival. A tailored intervention to promote RTW was launched in 2022. A year later, the women were contacted to find out if RTW had occurred regularly and what their health conditions were compared to baseline. BCSs reported excessive fatigue, poor sleep quality, anxiety, depression and reduced work ability; these parameters had not improved significantly compared to baseline. Thematic analysis of the interviews confirmed the presence of personal, company and societal factors that could hinder or favor RTW. The interviews demonstrated that, even in an economically developed country that has provided numerous benefits for BCSs, protection is not always effective. Personalized intervention seems necessary to complete the process of reintegrating BCSs into their future working careers.

Sugarcane mosaic virus (SCMV) and sugarcane streak mosaic virus (SCSMV) are the primary viruses responsible for mosaic diseases in sugarcane. In this study, the mosaic viruses SCMV and SCSMV with the involvement of sorghum mosaic virus (SrMV) were surveyed from eight commercial sugarcane cultivars grown in fields at four locations in East Java, Indonesia. Sugarcane leaves with mosaic symptoms were assessed for disease incidence and severity, and symptomatic leaves were collected for analysis. The incidence and severity of mosaic symptoms were the highest in the PS881 and NX04 cultivars grown in Kediri compared to the other cultivars. RT-PCR analysis showed that SCSMV was present in all sugarcane cultivars and locations. Interestingly, double mixed infections with SCMV were found in PS881, PS882, and Cening, whereas triple mixed infections with SrMV were found in the PS881 cultivar. Phylogenetic analysis grouped SCSMV, SCMV, and SrMV together with isolates from Thailand (KP987832.1), Florida, USA (MT725538.1), and Agentina (EU189037.1). The expression of ascorbate peroxidase gene (Apx) was increased in the virus-infected sugarcane cultivars and prominently elevated in the triple mixed infection of PS881 cultivars. However, the catalase gene (Cat) was slightly upregulated in the mixed infection group. The chlorophyll content was significantly reduced in the leaves of PS58, PS881, PS882, NX04, and HW Merah, in parallel with the expression of the photosystem I gene (PsaA). The expression of photosynthetic genes, such as ribulose-1,5 bisphosphate carboxylase small sub-unit (RbcS), phosphoenolpyruvate carboxylase (Pepc), sucrose-phosphate synthase (Sps1), and PsaA, was significantly reduced and almost depleted in the triple mixed infection of PS881, except for Pepc expression, which remained approximately half of that in the control healthy sugarcane. The decrease in photosynthetic activity was confirmed by the decrease in ribulose-1,5 bisphosphate carboxylase (Rubisco) and PEPC proteins, as detected by immunoblot analysis. The decrease in photosynthetic parameters indicated that the mosaic viral infection substantially reduced the growth and yield of sugarcane.

Fe-(9, 19, 28, 37)wt.% Cr alloys were corroded at 700 and 800 ^oC for 70 h under 1 atm of N₂, 1 atm of N₂/3.2%H₂O-mixed gas, and 1 atm of N₂/3.1%H₂O/2.42%H₂S-mixed gas. The corrosion rate of Fe-9Cr alloy increased with the addition of H₂O, and furthermore with the addition of H₂S in N₂ gas. Fe-9Cr alloy was always nonprotective. In contrast, Fe-(19, 28, 37) wt.%Cr alloys were protective in N₂ and N₂/H₂O-mixed gas because of formation of the Cr₂O₃ layer. They were, however, nonprotective in N₂/H₂O/H₂S-mixed gas because sulfidation dominated to form the outer FeS layer and the inner Cr₂S₃ layer containing some FeCr₂S₄.

Heptanuclear {GdIII7} (complex 1) and tetradecanuclear {GdIII14} (complex 2) have been synthesized using a Rhodamine 6G ligand HL (Rhodamine 6G salicylaldehyde hydrazone) and characterized. Complex 1 has a rare disc-shaped structure, where the central Gd ion was connected to the peripheral six GdIII ions via CH3O-/μ3-OH- bridges. Complex 2 has an unexpected three-layer double sandwich structure with a rare μ6-O2- ion in the center of the cluster. Magnetic studies revealed that complex 1 exhibits a magnetic entropy change of 17.4 J kg−1 K−1 at 3 K and 5 T. On the other hand, complex 2 shows a higher magnetic entropy change of 22.3 J kg−1 K−1 at 2 K and 5 T.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

Interactions between proteins and ions are essential for various biological functions like structural stability, metabolism, and signal transport. Given that more than half of all proteins bind to ions, it becomes crucial to identify ion-binding sites. Accurate identification of protein-ion binding sites helps us to understand proteins’ biological functions and plays a significant role in drug discovery. While several computational approaches have been proposed, this remains a challenging problem due to the small size and high versatility of metals and acid radicals. In this study, we propose IonPred, a sequence-based approach that employs ELECTRA (Efficiently Learning an Encoder that Classifies Token Replacements Accurately) to predict ion binding sites using only raw protein sequences. We successfully fine-tuned our pretrained model to predict the binding sites for nine metal ions (Zn2+, Cu2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Na+, and K+) and four acid radical ion ligands (CO32−, SO42−, PO43−, NO2−). IonPred surpassed six current state-of-the-art tools by over 44.65% and 28.46% respectively in F1 score and MCC when compared on an independent test dataset. Our method is more computationally efficient than existing tools producing prediction results for a hundred sequences for a specific ion in under ten minutes.

The reckless use of non-replenishable fuels by the growing population for energy and the resultant incessant emission of hazardous gases and waste products into the atmosphere insisted scientists to fabricate materials capable of managing these global threats at once. In recent studies, photo-catalysis employed focus on utilizing renewable solar energy to initiate chemical processes with the aid of semiconductors and highly selective catalysts. A wide range of nanoparticles have showcased promising photocatalytic properties. Ultrasmall metal nanoclusters (MNCs) with sizes below 2 nm, stabilized by ligands shows discrete energy levels, exhibits unique optoelectronic properties which are vital to photocatalysis. In this review, we intend to compile information on varying photocatalytic efficiency of metal NCs with respect to changes in their properties. Review discusses about the photocatalytic activity of atomically precise ligand-protected MNCs and its hybrids in the domain of in energy conversion processes like photodegradation of dyes, Oxygen Evolution Reaction (ORR), Hydrogen Evolution Reaction (HER) and CO2 Reduction Reaction (CO2RR), and photosensitizer in solar cell.

Background/Objective: Adequate serum vitamin D levels are essential for overall health, particularly in preventing oropharyngeal infections. This study aims to explore the relationship between serum vitamin D (25(OH)D3) levels and the prevalence of oropharyngeal diseases—specifically rhinosinusitis, otitis media, and nasopharyngitis—in patients at a private specialist medical clinic. Materials and Methods: The study involved 311 patients with an average age of 15.96±15.06 years. Statistical analyses, including Student's t-test and chi-square test, were conducted to evaluate the significance of the findings. Results: Nasopharyngitis was highly prevalent, affecting 83.27% of participants, with higher recurrence rates in those with lower vitamin D levels (p=0.001). Otitis media was present in 53.37% of cases, while rhinosinusitis was less common and more frequently associated with higher vitamin D levels. Patients with behavioral disorders had significantly higher mean vitamin D levels (34.82 ng/mL ±11.85) compared to those without (28.49 ng/mL ±14.37) (p=0.001). Conclusion: Lower serum vitamin D levels are associated with an increased incidence of oropharyngeal diseases. This study highlights the importance of maintaining optimal vitamin D levels for pediatric health and suggests that higher vitamin D levels may reduce the risk of oropharyngeal infections.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

To address the insufficient mechanical properties of calcined phosphogypsum, this research aims to investigate the utilization of basalt fiber and calcium carbonate whiskers as reinforcing agents. The study examines their impact on the flexural and compressive strength, toughness, water resistance, and tensile strength of calcined phosphogypsum. In the individual tests, basalt fibers with different lengths (3 mm, 6 mm, 9 mm, and 18 mm) were added at dosages of 0%, 0.5%, 1.0%, and 1.5% respectively. The findings demonstrate that basalt fiber effectively enhances the flexural and compressive strength, toughness, and tensile strength of calcined phosphogypsum, albeit potentially compromising water resistance. Among the various fiber lengths, the 6 mm fibers exhibit the most advantageous influence on the performance of calcined phosphogypsum. A subsequent test was conducted to investigate the impact of cross-scale fibers on the properties of calcined phosphogypsum by mixing 6 mm basalt fibers and calcium carbonate whiskers. The results illustrate that calcium carbonate whisker refines the pores, thereby improving the flexural strength and toughness of calcined phosphogypsum. Furthermore, it compensates for the water resistance limitations associated with the sole utilization of basalt fiber while further augmenting the tensile strength and strain capacity. However, it should be noted that increasing the dosage of both calcium carbonate whiskers and basalt fibers concurrently leads to increased porosity of phosphogypsum and reduced compressive strength.

Background: In Ethiopia, 8.6% of maternal deaths are attributed to abortion. Despite the legalization of abortion and improved accessibility of safe abortion services, almost six in 10 abortions in Ethiopia are performed outside of the health facility. Abortion considered as an indicator for various aspects of reproductive health and healthcare access within a particular region or country. Despite the significance of the problem, there is a limited understanding of the magnitude of abortion and the contributing factors in the study area. Therefore, this study aimed to assess the prevalence of abortion and determinant factors among reproductive-age women in the Sidama regional state of Ethiopia.Methods: A community-based cross-sectional study was conducted from October to November 11, 2022, among 1,130 women of reproductive age. We utilized a multi-stage sampling method to select eligible women. A structured and pretested questionnaire was utilized to collect the data using Open Data Kit (ODK) mobile application. Due to the hierarchical nature of the data, a multilevel logistic regression model was applied. Variables with p-values < 0.25 on bi-variable analysis were included in a multivariable regression model. In the multivariable regression model, variables with a p-value < 0.05 were declared as statistically significant factors of abortion. Results: Nearly one-fifth (19.5%) of the women had a history of abortion. From the individual level determinates; women with formal education (AOR=0.44; 95% CI: 0.24-0.79), and planned pregnancy (AOR=0.41; 95% CI: 0.28-0.61) had lower odds of abortion. While from the community related factors; urban residence increased the odds of abortion (AOR=2.25; 95% CI: 1.20-4.20) as compared to the rural residence.Conclusion: the prevalence of abortion among reproductive age women of Northern Zone of Sidama Region was high. Education and a planned pregnancy serve as protective factors for abortion, while the risk of abortion increased among women reside in urban area. Therefore, to lower the abortion rate, it is better to implement a comprehensive approach, focusing on education, family planning, and urban-specific intervention.

The expression of the oncogene zinc-finger protein 217 (ZNF217) has been reported to play a central role in cancer development, resistance, and recurrence. Therefore, targeting ZNF217 has been proposed as a possible strategy to fight cancer, making necessary to discover novel com-pounds. The present work aims to characterize the chemopreventive properties of cucurbitacin D , a compound with a broad range of anticancer effectsin relation to the ZNF217 expression. Different cucurbitacins were isolated from the Vietnamese plant Elaeocarpus hainanensis. The purified compounds were tested on nucleophosmin-mutated acute myeloid leukemia and other hematology cancer to study their effects on viability, apoptosis, cell cycle and on the expression of ZNF217. Cucurbitacin D reduced the number of acute myeloid leukemia cells by increasing apoptosis and blocking cell cycle progression. It also significantly decreased ZNF217 expression but only in the OCI-AML3 Nucleophosmin-mutated cell line, but not in other hematologic cancers. The reduction in ZNF217 expression contributed significantly to the blocking of cell cycle progression but not to apoptosis as established by the silencing of the same gene. The obtained results suggest Cucurbitacin D as a promising molecule to target the mutated Nu-cleophosmin or its pathway in acute myeloid leukemia cells, although further studies are needed for in depth investigatiion of its specificity.

Soot combustion experiments with 5%O2/He were conducted using model soot, and four distinct compositions of CexPr1-xO2-δ oxides were prepared, varying nominal cerium com-positions (x=0, 0.2, 0.3, and 1). The catalyst samples were comprehensively characterized using techniques such as XRD, Raman spectroscopy, HR-TEM, N2 adsorption at −196 °C, XPS, O2-TPD, H2-TPR, and work function measurements. The Pr-rich compositions, rang-ing from Ce0.3Pr0.7O2-δ to PrO2-δ, resulted in a significant increase in the total evolved O2 amounts and enhanced catalyst reducibility. However, a decrease in textural properties of the catalysts was noted, being particularly important for the pure praseodymia under the synthesis route conducted. The catalytic activity was investigated under two contact modes of mixing between soot and catalyst: loose and tight. The results revealed that the catalytic performance is associated with the surface contact in tight contact mode and with the combination of surface/subsurface/bulk oxygen mobility and the BET surface ar-ea in loose contact mode. Notably, the T10 and T50 parameters were achieved at much lower temperatures than the uncatalyzed soot combustion, even under loose contact conditions. Specifically, the 50% conversion was achieved at 511℃ and 538℃ for Ce0.3Pr0.7O2 and Ce0.2Pr0.8O2, respectively. While no direct correlation between catalytic activity and work function was observed a significant relationship emerges between work function values and the formation of oxy-gen vacancies, whatever the conditions used for these measurements. On the other hand, the ability to generate a high population of oxygen vacancies at low temperatures, rather than the direct activation of gas-phase O2, influences the catalytic performance of Pr-doped ceria catalysts, highlighting the importance of surface/subsurface oxygen vacancy generation, which was the parameter which showed better correlation with the catalytic activity, whatever the soot conversion value or the mode of contact considered.

Background: This study was designed to adapt the Delis-Kaplan Executive System (D-KEFS) version of the Color-Word Interference (CWIT) and Trail making Tests (TMT) in Greek adult population from 20 to 49 years old, since it is of research as well as clinical importance to detect executive functions’ impairment in young adults with neurological or/and psychiatric conditions. Aims: Norms for the Greek adult population have been calculated to be available for neuropsychologists and health professionals who work in relevant settings. Methods: The study sample consisted of 101 healthy adults (41% male and 60% female), aged 20 to 49 years (M=32.16, SD=11.57) with education from 12 to 19 years of schooling (M=14.51, SD= .89). Pearson correlation test as well as chi square test were conducted to examine potential associations between gender, age, education, and participants’ performance. Afterwards, we calculated normative data using raw scores and transformed them to percentile scores. Finally, Greek norms were compared to the original raw scores, which were transformed in scaled scores by Delis et al. (2001). Results: The findings showed that age was the only variable which affected CWIT, whereas level of education as well as age were predictive factors for most TMT conditions, except for the visual scanning test (Condition 1). Gender did not affect both tests. Finally, D-KEFS norms for CWIT and TMT are available for Greek adult population to help clinicians detect executive functions’ deficits and therefore adjust tailored therapeutic strategies. Additionally, it is of great importance to use these tests for research purposes. Conclusion: Given that executive functions are assumed as high- level skills, which are highly related to everyday functionality, adapted tests contribute not only to assess the progression of any existing neurological as well as psychiatric disorders, but they can also be used to evaluate patients’ ability to live independently, as well as their access to work.

This study aimed to evaluate the effect of three yeast strains, Pichia guilliermondii (Levica 27), Candida norvegensis (Levazoot 15), and a commercial product (Levucell® SC 10) containing Saccharomyces cerevisiae, on in vitro rumen fermentation of two substrates: corn stover and a total mixed ration (TMR). Samples were taken 24 hours post-fermentation to measure pH, ammonia nitrogen (NH3-N), gas production, and volatile fatty acid (VFA) concentrations. The addition of yeasts did not affect gas production at 24 hours for either diet. For pH, differences between yeast strains were noted when TMR was used. The lowest NH3-N concentration (6.1 mM) was recorded with corn stover, showing similar results across strains. Conversely, NH3-N levels with TMR ranged from 47 mM to 66 mM. The inclusion of all three yeast strains increased the molar concentrations of total VFA, as well as acetic (C2), propionic (C3), and butyric (C4) acids in the rumen fluid. The C2:C3 ratio remained unchanged with corn stover but decreased with the inclusion of Levica 27 and Levazoot 15 in the TMR. With the commercial product Levucell® SC 10, this ratio was comparable to the control treatment. In conclusion, Levica 27 and Levazoot 15 demonstrated a stimulatory effect on in vitro rumen fermentation for the evaluated diets, evidenced by increased VFA concentrations.

Until now, Z-form RNAs were believed to only adopt a left-handed double helix structure. In this study, we describe the first observation of a right-handed Z-form RNA in NMR solution formed by L-nucleic acid RNA and present the first resolution structure of the complex between a right-handed Z-form RNA and a curaxin ligand. This newly described topology is of great interest as it shows that Z-form RNAs can also adopt a right-handed double helix structure and interact with ligand molecules. The structural information provides a platform for the design of topology specific Z-form-targeting compounds and is valuable for the development of new potent anticancer drugs.

The optimization of ligand-receptor binding affinities is essential for enhancing therapeutic efficacy and specificity, particularly in the design of peptide-based drugs. ziconotide, a potent blocker of the N-type calcium channel CaV2.2, has demonstrated therapeutic potential in the treatment of moderate to severe chronic pain. However, there is limited structural and binding affinity data available for scaling the design of ziconotide analogues with improved efficacy and specificity. In this study, I present a structural biophysics-based approach to develop a scalable in silico framework for generating and analyzing ligand-receptor binding affinity landscapes, focusing on ziconotide and its receptor, CaV2.2. This framework integrates advanced computational structural tools and binding affinity calculations to produce high-accuracy structural and intermolecular binding data. The insights gained from this scalable approach will guide the design of ziconotide analogues with enhanced efficacy, offering a powerful computational workflow for high-throughput ligand optimization. Additionally, when combined with artificial intelligence (AI) algorithms, this computational workflow generates high-accuracy structural and biophysical data, towards an AI- and structural biophysics-driven paradigm shift in peptide discovery and design.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

With the advancement of technology, signal modulation types are becoming increasingly diverse and complex. The phenomenon of signal time-frequency overlap during transmission poses significant challenges for the classification and recognition of mixed signals, including poor recognition capabilities and low generality. This paper presents a recognition model for fine-grained analysis of mixed signal characteristics, proposing a Geometry Coordinate attention mechanism and introducing a low-rank bilinear pooling module to more effectively extract signal features for classification. The model employs a residual neural network as its backbone architecture and utilizes the Geometry Coordinate attention mechanism for time-frequency weighted analysis based on information geometry theory. This analysis targets multiple-scale features within the architecture, producing time-frequency weighted features of the signal. These weighted features are further analyzed through a low-rank bilinear pooling module, combined with the backbone features, to achieve fine-grained feature fusion. This results in a fused feature vector for mixed signal classification. Experiments were conducted on a simulated dataset comprising 39,600 mixed signal time-frequency plots. The model was benchmarked against a baseline using a residual neural network. The experimental outcomes demonstrated an improvement of 9% in the exact match ratio and 5% in the Hamming score. These results indicate that the proposed model significantly enhances the recognition capability and generalizability of mixed signal classification.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via immunological modulations. Here, we summarize the molecular, cellular, and clinical implications of IDH mutations in gliomas as well as current diagnostic techniques.

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

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

Background/Objectives: Women's reproductive and overall well-being are intricately associated to vitamin D levels. In Morocco, vitamin D deficiency is a major issue for premenopausal women, yet little data exists on their dietary intake of this nutrient. This study explores vitamin D dietary intake, socio-demographic determinants, and its correlation with serum 25-hydroxyvitamin D [25(OH)D3] in premenopausal Moroccan women. Methods: A cross-sectional study was conducted with 355 women aged 18-49 in Meknes, Morocco, using validated questionnaires to assess dietary intake and sun exposure. Potential covariates such as physical activity and BMI were also assessed . Serum 25(OH)D was measured via chemiluminescence immunoassay. Chi-square tests and Spearman correlation were used to identify socio-demographic factors influencing vitamin D intake. Linear and multivariate regression analysis determined the main predictors of serum 25(OH)D levels. Results :The median (interquartile range) vitamin D dietary intake was 2.8 (2.7) µg/day , with less than 20% of women meeting the recommended 5 µg/day. Major dietary sources were fish (48%), dairy (24.3%), and meat (9.4%), with fortified foods contributing only for 7%. Lower intake was linked to younger age (p=0.004) and rural living (p=0.024). While no significant association was found between dietary intake and serum 25(OH)D ((β(SE): 0.155(0.094), p=0.340 ) , sun exposure positively predicted serum levels(β(SE): 0.343 (0.128), p=0.008) , and BMI negatively affected them (β(SE): -1.128 (0.337), p=0.001). Conclusions: Our findings highlight insufficient vitamin D intake among premenopausal Moroccan women, especially younger and rural women. Nutritional interventions are needed to address this deficiency, promoting better dietary habits, sun exposure, and healthy weight.

This paper describes the first results of an Image Recognition Based Location (IRBL) for mobile application focusing on the procedure to generate a Database of range images (RGB-D). In an indoor environment, to estimate the camera position and orientation, a prior spatial knowledge of the surrounding is needed. In order to achieve this objective a complete 3D survey of two different environment (Bangbae metro station of Seoul and E.T.R.I. building in Daejeon – Republic of Korea) was performed using LiDAR (Light Detection And Ranging) instrument and the obtained scans were processed in order to obtain a spatial model of the environments. From this, two databases of reference images were generated using a specific software realized by the Geomatics group of Politecnico di Torino (ScanToRGBDImage). This tool allow to generate synthetically different RGB-D images) centered in the each scan position in the environment. Later, the external parameters (X, Y, Z, ω, φ, κ) and the range information extracted from the DB images retrieved, are used as reference information for pose estimation of a set of acquired mobile pictures in the IRBL procedure. In this paper the survey operations, the approach for generating the RGB-D images and the IRB strategy are reported. Finally the analysis of the results and the validation test are described.

Electrochromic measurements have been performed throughout the full composition range of reactive magnetron-sputtered mixed Titanium oxide and Molybdenum oxide (TiO2-MoO3) to search for enhanced Coloration Efficiency (CE). Optical parameters and composition have been determined and mapped by using Spectroscopic Ellipsometry (SE). Scanning Electron Microscopy (SEM) with Energy-Dispersive X-ray Spectroscopy (EDS). EDS has been used to check the SE results as it was used in our earlier paper [N. T. Ismaeel et al, Materials 2023, 16(12), 4204] for (TiO2-SnO2). Ti and Mo targets were put separately from each other, and the Indium-Tin-Oxide (ITO) covered glass and Si-probes on a glass substrate (30 cm × 30 cm) were moved under the two separated targets (Ti and Mo) in a reactive Argon-Oxygen (Ar-O2) gas mixture. By using this combinatorial process, all the compositions (from 0 to 100%) were achieved in the same sputtering chamber after one sputtering process. The CE (the change of light transmission for the unit electric charge) of mixed metal oxides (TiO2-MoO3) that are deposited by reactive sputtering has been studied in an electrochemical cell. This paper aims to assess the results of investigations of such materials showing the enhanced electrochromic behavior compared to the pure materials and to enhance the Coloration Efficiency.

The aim of this single-center, open-label, non-controlled randomized study was to evaluate which formulation of vitamin D between cholecalciferol and calcifediol is most effective in the treatment of hypovitaminosis D in older adults. Demographic characteristics, clinical history and comprehensive geriatric assessment were recorded at admission. Eligible patients randomly received an equivalent vitamin D supplement either with cholecalciferol or calcifediol from hospital admission to three months after discharge. Among the 140 older patients included (mean age 83±6.6, 57.8% females), 69 received cholecalciferol and 71 calcifediol. The mean plasma values of 25OH-Vitamin D3 found at the enrollment were 16.8 ± 9.9 ng/mL in patients receiving cholecalciferol and 18.8 ± 13.3 ng/mL in those treated with calcifediol (p =0.31). At the 3-month follow up, the mean concentration of 25OH-Vitamin D3 was significantly higher in patients treated with calcifediol than in patients treated with cholecalciferol (respectively, 30.7 ± 8.4 vs 45.4 ± 9.8 ng/mL, p &lt;0.001). Supplementation with cholecalciferol or calcifediol results in both cases effective in reaching optimal circulating values of 25OH-VitaminD3 in the older patients suffering from hypovitaminosis D. However, supplementation with calcifediol led to average circulating values of 25OH- VitaminD3 significantly higher (over 50%) than those obtained with cholecalciferol.

Hybrid power plants have recently emerged as reliable and flexible electricity generation stations by combining multiple renewable energy sources, energy storage systems (ESS), and fossil-based output. However, the effective operation of the hybrid power plants to ensure continuous energy dispatch under challenging conditions is a complex task. This paper proposes a dispatch engine (DE) based on mixed-integer linear programming (MILP) for the planning and management of hybrid power plants. To maintain the committed electricity output, the dispatch engine will provide schedules for operation over extended time periods as well as monitor and reschedule the operation in real-time. Through precise prediction of the PV and wind power output, the proposed approach guarantees optimum scheduling. The precise prediction of the PV and wind power are achieved by employing a predictor of Feed-Forward Neural Network (FFNN) type. With such a dispatch engine, the operational cost of the hybrid power plants, and the use of diesel generators (DGs) are both minimized. A case study is carried out to assess the proposed dispatch engine feasibility. A real-time measurement data pertaining to load, wind, and PV power outputs is obtained from different locations in the Sultanate of Oman. The real-time data is utilized to predict the future output power from PV and the Wind farm over 24 hours. The predicted powers are then used in combination with a PV-Wind-DG-ESS-Grid hybrid plant to evaluate the performance of the proposed dispatch engine. The proposed approach is implemented and simulated using MATLAB. The results of the simulation reveal the proposed Feed-Forward Neural Network’s (FFNN) powerful forecasting abilities. In addition, the results demonstrate that adopting the proposed DE can minimize the use of DG units and reduce plant running expenses.

Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favour thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of the study was to analyse the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with compared with those without ARDS and inversely associated with LPS. In COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp, and LPS and D-Dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/Albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers, that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation and low serum albumin may account for low-grade endotoxemia, and they may be implicated in thrombotic events in COVID-19.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of Vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the determination of Vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. Additionally, given the important interrelations between Vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Diarylethene is a prototypical molecular switch that can be reversibly photoisomerized between its open and closed forms. Ligands bpy-DAE-bpy, consisting of a phenyl-diarylethene-phenyl (DAE) central core and bipyridine (bpy) terminal substituents, are able to self-organize. They are investigated by scanning tunneling microscopy at the solid-liquid interface. Upon light irradiation, cooperative photochromic switching of the ligands is recognized down to the sub-molecular level. The closed isomers show different electron density of states (DOS) contrasts, attributed to the HOMO or LUMO molecular orbitals observed. More importantly, the LUMO images show remarkable differences between the open and closed isomers, attributed to combined topographic and electronic contrasts mainly on the DAE moieties. The electronic contrasts from multiple HOMO or LUMO distributions, combined with topographic distortion of the open or closed DAE, are interpreted by density functional theory (DFT) calculations.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

The global population is at risk of vitamin D deficiency due to low exposure to sunlight and low intake of the vitamin through diet. The aim was to investigate in women the association between vitamin D status and parathyroid hormone (PTH), ultraviolet radiation, lifestyle, ethnicity, social conditions, and residential greenness. A 1-year longitudinal study assessed vitamin D status in 309 women, latitude 51° 14' N. Blood samples were taken four times throughout the year for analysis of 25(OH)D and serum PTH concentration. After each seasonal visit, the individuals completed 4-day diet diaries and used two dosimeter badges for 1 week to estimate weekly UVR exposure. A questionnaire was applied to provide information about lifestyle and their ethnicity. Residential greenness was measured by Normalized Difference Vegetation Index (NDVI), within a 1000 m radius around each participant’s home address. Women living in greener spaces were more likely to have improved vitamin D status (RR: 1.51; 95%CI: 1.13 – 2.02), as well as those who were more exposed to UVR (RR: 2.05; 95%CI: 1.44 – 2.92). Our results provided a first insight into the connection between vitamin D, residential greenness, and lifestyle in a region of temperate climate and with a high degree of urbanization.

Mixed plastic packaging waste sorting residues (MPO323) were treated by thermal pyrolysis to utilize pyrolysis oil and char. The pyrolysis oil was found to contain aromatic and aliphatic hydrocarbons. Chlorine and bromine contents were up to 40,000 mg/kg and 200 mg/kg, respectively. Additionally, other elements like sulfur, phosphorous, iron, aluminum, and lead were detected, which can be interpreted as impurities regarding the utilization of the oils by means of chemical recycling. The pyrolysis char showed high contents of potentially active species like silicon, calcium, aluminum, iron, and others. To enhance the content of aromatic hydrocarbons and to reduce the level of contaminants, the pyrolysis oil was reformed with the corresponding pyrolysis char to act as an active material in a fixed bed. The temperature of the reactor and the flow rate of the pyrolysis oil feed were varied to gain insights on cracking and reforming reactions as well as on the performance with regard to decontamination.

Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.

Three monoruthenium complexes 1(PF6)23(PF6)2 bearing a N(CH3)-bridged ligand have been synthesized and characterized. These complexes have a general formula of [Ru(bpy)2(L)](PF6)2, where L is a 2,5-di(N-methyl-N-(pyrid-2-yl)amino)pyrazine (dapz) derivative with various substituents and bpy is 2,2′-bipyridine. The photophyscial and electrochemical properties of these compounds have been examined. The solid-state structure of complex 3(PF6)2 is studied by single crystal X-ray analysis. These complexes show two well-separated emission bands centered at 451 and 646 nm (max = 195 nm) for 1(PF6)2, 465 and 627 nm (max = 162 nm) for 2(PF6)2, and 455 and 608 nm (max = 153 nm) for 3(PF6)2 in dilute acetonitrile solution, respectively. The emission maxima of the higher-energy emission bands of these complexes are similar, while the lower-energy emission bands are dependent on the electronic nature of substituents. These complexes display two consecutive redox couples owing to the stepwise oxidation of the N(CH3)-bridged ligand and ruthenium component. In addition, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations are carried out to elucidate these experimental findings.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility and differentiation. Dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of ligand without assuming that the mutations induce receptor dimerization. In this review, we discuss mechanisms underlying ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.

Background/Objectives: Type 1 Diabetes Mellitus (T1DM) is the reduction or non-production of insulin. As T1DM increases cardiovascular risk, in addition to glycemic control, the monitoring of other risk factors, such as lipid profile, has gained attention. Vitamin D deficiency has been associated with the pathophysiology of T1DM, metabolic syndrome, and cardiovascular diseases. This study investigated the relationship between vitamin D, glycemic control, and lipid profiles in children and adolescents with T1DM. Methods: This observational study consisted of 81 patients with T1DM. Laboratory test data were collected to determine the lipid profile. Glycated hemoglobin (HbA1c) and fasting glucose levels assessed glycemic control. Results: A significant association was observed between serum vitamin D levels and a pubertal stage and a moderate negative correlation between vitamin D, age, and HbA1c. There is a negative correlation between vitamin D levels and age, as well as with HbA1c, and a positive correlation of HbA1c with glucose, total cholesterol, triglycerides, Low-density lipoprotein (LDL-c), non-HDL cholesterol (non-HDL cholesterol), apolipoprotein B (apoB), and the apolipoprotein B/apolipoprotein A ratio. Finally, the study indicated that vitamin D levels, insulin administration method, and total cholesterol, when considered together, explained approximately 43.6% of the observed variation in HbA1c, highlighting the complex interdependence of these factors in regulating glycemia. Conclusions: Our results show that Vitamin D levels are associated with glycemic control and other biochemical parameters and its control can bring benefits to the patient with T1DM.

The aim of this study is to characterize the compound extremes of rainfall and temperature in Côte d’Ivoire. For this purpose, we analyzed the outputs of fourteen (14) climate models from the CORDEX-Africa project. Results show an increase (approximately 4.3°C) of the surface temperature and a decrease (5,90 %) of the mean rainfall in the near (2036-2065) and far futures (2071-2100) over Côte d’Ivoire during January-February-March (JFM) period. The analysis of the compound extremes of wet/warm type highlights an increase in the frequency of this climatic hazard in the northern and central parts of the country during January-March (JFM) season in the near and far futures. The dry/warm mode will increase in the central and southern parts of the country during the near future and in the whole country during the far future. These increase in compound extremes could lead to an increase in droughts and natural disasters over the country and could have a negative impact on socio-economic activities, such as transportation and agricultural production. This work could provide decision support for political decision-makers in formulating future public policies for managing agricultural production, food security, and natural disasters.

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositols may influence oocyte maturation, improve intracellular Ca2⁺ oscillation in the oocytes and have been proposed as potential interventions for restoring spontaneous ovulation. MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase thus regulating androgen synthesis. Under physiological conditions, MYO/DCI ratio is maintained at 40:1 in the plasma. In women with PCOS, MYO/DCI ratio lowers to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositols may be a promising strategy to address female infertility and sustain healthy pregnancy.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Cyclooxygenases (COX), or prostaglandin endoperoxide synthases (PTGS), are key enzimes in the synthesis of prostaglandins, which are chemical species critical in mediating inflammatory processes. There are two highly homologous COX isoforms: COX-1 and COX-2. COX-1 is involved in the production of prostaglandins, chemical compuounds that take part in physiological processes such as: protection of the gastric epithelium, maintenance of renal flow, platelet aggregation, neutrophil migration and, also, are expressed in the vascular endothelium. Meanwhile, COX-2 is induced by proinflammatory stimuli. It is very frequent the use of nonsteroidal antiinflammatory drugs (NSAIDs) to counteract the symptoms of inflammatory processes. These drugs, in addition to its benefits, can cause side effects on people’s health, such as cardiovascular and respiratory problems, among others. In the past years, it has been recognized the potential of plants secondary metabolites as pharmacological agents, prompting the need for investigations that shed light into its mechanism of action. In this work we have applied computational techniques, based on quantum chemistry and mechanical statistics, to study the protein-ligand interaction involving COX’s and secondary metabolites from natural sources. Our aim is to determine the structure activity interplay in processes involving the participation of secondary plant metabolites such as luteolin, galangin, kaempferol, apigenin, morine and quercetin on the inactivation of COX’s. From molecular docking analysis, we have extracted the energetics of the COX-(1,2)/metabolite coupling. By defining energy based factors, we have determined a procedure that predicts the chemical species with highest stability and selectivity towards inactivation of COX-2 over COX-1. The results are discussed with regard to conformational features of the selected ligands and its intermolecular strong/weak interactions inside the active-sites of the COX’s hosts.

Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases evolving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like receptors). Fifteen structurally diverse ligands were docked to these models. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for DR sub-type specificity. Results: We showed that the number of conformations for a receptor:ligand complex was associated to unspecific interactions > 2.5 Å and hydrophobic contacts, while the decoys binding energy was influenced by specific electrostatic interactions. Known residues such as 3.32Asp, the serine microdomain and the aromatic microdomain were found interacting in a variety of modes (HB, SB, π-stacking). Purposed TM2-TM3-TM7 microdomain was found to form a hydrophobic network involving Orthosteric Binding Pocket (OBP) and Secondary Binding Pocket (SBP). T-stacking interactions revealed as especially relevant for some large ligands such as apomorphine, risperidone or aripiprazole. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, key for the design of more specific ligands.

Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples (including leaf, fruit and seed) were analysed in duplicate for vitamin D₂, vitamin D₃, 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃. Five samples contained vitamin D₂: raw wattleseed (Acacia victoriae) (0.03 µg/100 g dry weight (DW)); fresh and dried lemon myrtle (Backhousia citriodora) leaves (0.03 and 0.24 µg/100 g DW, respectively); dried leaves and berries of Tasmanian mountain pepper (Tasmannia lanceolata) (0.67 and 0.05 µg/100 g DW, respectively). Fresh kombu (Lessonia corrugata) contained vitamin D₃ (0.01 µg/100 g DW). Detected amounts were low; however, it is possible that exposure to ultraviolet radiation may increase the vitamin D content of plants and algae if vitamin D precursors are present.

Background: According to newly published studies, patients with Coronavirus Disease 2019 (COVID-19) have significantly lower serum 25-hydroxyvitamin D 25(OH)D levels than those without the SARS-CoV-2 infection. Vitamin D insufficiency may be a predictor of poor prognosis in COVID-19 patients. Vitamin D supplementation is related to improved clinical outcomes in terms of intensive care unit (ICU) admission and death, particularly in individuals with moderate-to-severe forms of COVID-19 requiring hospitalization. Materials and methods: This placebo-controlled five-day study was performed on 100 hospitalized COVID-19 patients with vitamin D insufficiency randomized into two groups. Vitamin D in the form of a sublingual sprayable microemulsion (LYL love your life® sunD3 LYLmicro™) was given three times daily after breakfast, lunch, and dinner (daily dose 12,000 IU) to 52 patients with blood vitamin D levels below 30 ng/ml. 48 patients in the control group received a placebo spray in the same daily regiment. Results: We observed a statistically significant increase by 8.6 ng/ml in median vitamin D level after five days of high-dose vitamin D3 spray therapy. 90.2% of subjects reached normal serum levels of vitamin D. There was a strong correlation between changes in vitamin D and C-reactive protein (CRP) levels in individuals with moderately severe disease (p<0.05), while mild and severe cases showed no statistical significance comparing case and control groups. There were no statistically significant changes in ferritin and interleukin-6 (IL-6) levels. Conclusions: In this study, we demonstrated the possibility to rapidly increase circulating levels of vitamin D just in 5 days of high-dose intervention and found a statistically significant decrease of CRP levels in patients with moderately severe COVID-19. We were not able to detect statistically significant changes in ferritin and IL-6 levels during the 5-day vitamin D intervention.

1) Background: The aim was to evaluate the bioefficacy of vitamin D (VitD) encapsulated in nanoemulsions developed by sonication and pH-shifting of pea protein isolate in restoring VitD status in VitD-deficient rats. 2) Methods: Weaned (3-week old), male albino rats (n = 35) were initially divided into two groups: control sufficient group (VDS; n = 7) fed on a normal AIN-93G diet and a VitD-deficient group (n = 28) fed a VitD-deficient diet for six weeks. VitD-deficient rats were divided into four subgroups: two treatment groups (Nano+VitD and Oil+VitD) and two control groups (Nano-VitD and Oil-VitD), receiving seven rats in each sub-group. Nano+VitD and Oil+VitD groups received VitD dispersed in PPI-nanoemulsions and in canola oil, respectively, while the control groups received the respective delivery vehicles without VitD. Serum 25-hydroxyvitamin D [25(OH)VitD], parathyroid hormone (PTH), calcium (Ca), phosphorus levels (P), and alkaline phosphatase (ALP) activity were measured. Femur bone was used to prepare histopathological sections. 3) Results: After one week of treatment, the VitD-deficient rats consuming Nano+VitD recovered from VitD deficiency (serum 25(OH)VitD 34.38 ± 7.00) compared to the sufficient control (36.84 ± 9.16; p > 0.05) and the deficient control consuming VitD+Oil (14.05 ± 3.08; p < 0.01). Enhancement in VitD status was followed with expected changes in serum PTH, Ca, P, and ALP levels, no difference in similar biomarkers against the sufficient control, and an improvement of the osteoid area and reduction of trabecular separation in bone. 4) Conclusions: Stabilization of VitD within PPI-based nanoemulsions enhances its absorption and restores its status and biomarkers of bone resorption in VitD-deficient rats.