Biochar application to the soil can improve soil quality and nutrient leaching loss. Recent studies have reported that surficial application of biochar to stored swine manure can reduce emissions of odorous compounds and reduce the volatilization loss of ammonia. Our working hypothesis was that the biochar-treated manure application to the soil would decrease nutrient leaching from manure and increase plant-available nutrients. The study objectives were to evaluate the impact of biochar-treated swine manure on soil total C, N, and other major and minor nutrients. Three biochars (i) neutral pH red-oak (RO), (ii) highly alkaline autothermal corn (Zea mays) stover (HAP), and (iii) mild acidic Fe-treated autothermal corn stover (HAPE) were incubated with swine manure for a month. The biochar-manure mixture was applied in triplicate to soil columns with application rate determined by the P₂O₅-P content in manure or manure-biochar mixtures after the incubation. The ammonium (NH₄⁺), nitrate (NO₃^-), and reactive P concentrations in soil column leachates were recorded for eight leaching events. Soil properties and plant-available nutrients were compared between treatments and control manure & soil. Manure-(HAP&HAPE) biochar treatments significantly increased soil organic matter (OM) and increased soil total C, N, and improved soil bulk density. Concentrations of KCl-extractable NH₄⁺ and NO₃^- significantly increased in HAPE column leachates during this 4-week study and in the soil after the experiment. A significant reduction in soil Mehlich3 Cu was also observed for the manure-HAPE mixture compared with the control. Overall, the manure-biochar incubation enabled biochar to sorb nutrients from manure, and the subsequent manure-biochar mixture application to soil improved soil quality and plant nutrient availability in comparison to conventional manure application to soil. This proof-of-the-concept study suggests that biochars could be used to solve both environmental and agronomic challenges and further improve the sustainability of animal and crop production agriculture.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

The over use of pharmaceutical compounds, essentially antibiotics, led to an increase of their concentrations in aquatic ecosystems. In this study, the white-rot fungus Coriolopsis gallica (high-laccase-producing fungus) was investigated for the biodegradation of ampicillin (AMP) under different cultivation conditions. The biotransformation of the antibiotic was confirmed by means of high-performance liquid chromatography (HPLC), and the antibacterial activity was evaluated via the bacterial growth inhibition agar well diffusion method using Escherichia coli as an ampicillin-sensitive test strain. The results showed that AMP (50 mg L-1) was totally removed by C. gallica after 6 days of incubation in a liquid medium. The antibiotic removal rate was maximal with a fungal culture aged 9 days. Such a culture achieved the removal of a higher concentration of up to 500 mg L-1 of ampicillin in 3 days. This higher antibiotic removal rate was concomitant with the maximal laccase production in culture supernatant. In addition, four consecutive doses of 500 mg L-1 of ampicillin were transformed by the same fungal culture in 24 days. After that, the fungus was unable to remove the antibiotic. The measurement of ligninolytic enzyme activity showed that laccase of C. gallica might participate in the biotransformation of AMP.

The protein TRPM8, a non-selective, calcium (Ca2+) permeable ion channel is implicated in several pathological conditions, including neuropathic pain states. In our previous research endeavors, we have identified β–lactam derivatives with high hydrophobic character that exhibit potent and selective TRPM8 antagonist activity. This work describes the synthesis of novel derivatives featuring C-terminal amides and diversely substituted N’-terminal monobenzyl groups, in an attempt to increase the total polar surface area (TPSA) in this family of compounds. The primary goal was to assess the influence of these substituents on the inhibition of menthol-induced cellular Ca2+ entry, thereby establishing critical structure-activity relationships. While the substitution of the tert-butyl ester by isobutyl amide moieties improved the antagonist activity, none of the N’-monobencyl derivatives, regardless of the substituent on the phenyl ring, achieved the activity of the model dibenzyl compound. The antagonist potency of the most effective compounds was subsequently verified using Patch-Clamp electrophysiology experiments. Furthermore, we evaluated the selectivity of one of these compounds against other members of the TRP ion channel family and some receptors connected to peripheral pain pathways. This compound demonstrated specificity for TRPM8 channels. To better comprehend the potential mode of interaction, we conducted docking experiments to uncover plausible binding sites on the functionally active tetrameric protein, which come upon four main poses by the pore zone, differents from those described for other known antagonists. Finally, in vivo experiments, involving a couple of selected compounds, revealed significant antinociceptive activity within a mice model of cold allodynia induced by oxaliplatin.

Forty-five male Dorper crossbred lambs (40.17 ± 0.35 kg BW) were used in order to investigate the effects of the duration of calcium propionate (CaPr) supplementation in lambs finished with zilpaterol hydrochloride (ZH) on the productive performance, carcass characteristics, and meat quality. Lambs were individually housed and fed a finishing-diet for 42 d before being slaughtered. Lambs received the following treatments: 1) No additives (CTL), 2) ZH supplementation for 28 d (with 3 d ZH withdrawal before slaughter) at a dosage of at 7.2 mg/kg diet (ZH), for treatments 3, 4, and 5, lambs received ZH and 10g CaPr/lamb/d throughout the entire phase (42 d), or during the last 28 or 14 d before slaughter. Compared to CTL, ZH lambs exhibited a similar average daily gain (ADG) but had lower dry matter intake (DMI), leading to increased feed efficiency. Supplementing with ZH alone did not affect carcass traits, visceral mass, whole cuts, or meat quality. Lambs that received both CaPr and ZH exhibited quadratic increases (p < 0.05) in final BW (FBW), ADG, and dressing percentage (D%). These increases were optimal at an estimated inclusion durations of 26 d for FBW, 30 for ADG, and 39 d for D%. The ADG:DMI ratio and the longissimus muscle area (LMA) both exhibited quadratic increases (p < 0.05). The optimal duration of CaPr supplementation for ADG:DMI ratio was found to be 28 d, while for LMA, it was 14 d. As the period of CaPr supplementation increased, there was a linear increase (p <0.05) in hot carcass weight, leg circumference, and whole cuts of breast IMPS209 and shoulder IMPS207. Cook loss percent increased quadratically (p < 0.05), being higher when CaPr was included for an estimated duration of 26 d. As the duration of CaPr supplementation increased, the purge loss percentage (PLR) also increased linearly (p < 0.05). In conclusion, including CaPr in the diet for a duration of 28 d in lambs improved the response to ZH supplementation on the productive performance, carcass weight and some whole cuts. However, it can also have a negative effect on PRL%.

This study presents an innovative analytical method for the detection and quantification of 14 β-agonists in pork using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method involves the use of a solid phase microextraction (SPME) probe, consisting of a wooden tip coated with polyacrylonitrile (PAN) and molecularly imprinted polymer (MIP). This probe has been integrated into an automated extraction device, designed in our laboratory to extract the target analytes prior to LC-MS/MS analysis. Compared to the traditional solid-phase extraction (SPE) procedure, the proposed approach significantly reduces the costs related to adsorbent ma-terial and solvent consumption, and shortens purification time, thereby reducing both the tech-nical workload and associated expenses. The methodology has been carefully validated in ac-cordance with the National Standard of the People's Republic of China (GB/T 22286-2008), evalu-ating key parameters including the limit of detection (LOD), limit of quantification (LOQ), matrix effects, linearity, and both intra-day and inter-day precision. The average recovery rates for all β-agonists were observed to lie between 71.6% and 82.2%, with relative standard deviations (RSDs) consistently below 15% for both types of precision. The LOD and LOQ values were found to range from 0.09 to 0.39 μg/kg and 0.27 to 0.99 μg/kg, respectively. In terms of accurate detection of positive samples, the developed method demonstrated a closer approximation to the true value of the sample compared to the National Standard method GB/T 31658.22-2022. Overall, the proposed method exhibits substantial promise for the routine assessment of β-agonists in pork and presents a practical alternative for compliance monitoring in regulatory settings.

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM) - Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus - cultivated on a barley medium, was assessed for its anti-AD effects. A neuron-like PC12 cells, which were subjected to Zn2+, an Aβ aggregator, was employed as an in vitro AD model. The cells pretreated with or without MMMM assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and increment in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaques accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation, and neuroinflammation, by impeding Aβ-induced neurotoxicity.

Enzyme immobilization is known to enhance polypeptide resistance towards environmental changes, particularly in terms of their stability. The Y509E mutant of β-xylosidase from Geobacil-lus stearothermophilus (XynB2Y509E) (which also bears xylanase activity) has been immobilized in chitosan spheres through either entrapment or covalent bond formation methods. In the immo-bilization by entrapment, besides observing a total loss of xylanase activity, it was found that chitosan concentration affects the process efficiency. Additionally, the maturation time of the spheres and the alkaline pH used to precipitate the spheres affect the β-xylosidase activity of the enzyme. In covalent bond immobilization, it was found that the pH during the modification with glutaraldehyde, as well as the subsequent protein binding, were key factors in preserving the dual enzymatic activity. The activity expressed after immobilization by covalent bonding was 23% higher compared to the activity expressed following entrapment immobilization, with values of 122.3 and 99.4 U. g-1, respectively. Both biocatalysts showed increased thermal and pH stability, along with an improved storage capacity, as they retained 40% and 88% of their activi-ty after being stored at 4 C for two months. Moreover, XynB2Y509E immobilized by covalent binding also exhibited outstanding reusability, retaining a 92% of activity after ten cycles of re-use.

β-thalassemia, a congenital genetic hematological disorder characterized by decreased or absence of β-globin chains, leads to decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications arising due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to the iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, we critically evaluate the therapeutic efficacy of different iron chelators, emphasizing their respective advantages in managing iron overload complications. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia.

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥ 1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, β-HCG, and HbA1C was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with increase in β-HCG and HbA1C, and decrease of total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wildtype (+/+) and knockout (-/-) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of PEPCK mRNA independent of genotype, while increasing CPT1 mRNA only in GPR109a -/- mice. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and -/- mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator activated receptor α (PPARα) mRNA expression. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the ketogenic state or the pharmacological benefits associated with niacin.

The transforming growth factor-β (TGF-β), in which overexpression have been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Three series of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–h, 15a–h, 16a–h, 22a, 22b, 22d, 23a, 23b, 23d, 24b, and 24d were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activity in an enzymatic assays. Among these compounds, the most active compound 16f inhibited ALK5 phosphorylation with an IC₅₀ value of 0.28 µM, with 98% inhibition at 10 µM. Compound 16f also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). Molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.

As a chronic disease, osteoarthritis (OA) leads to degradation of both cartilage and subchondral bone, of which the development is related to proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of Specnvezhenide in osteoarthritis and mechanism of it was studied in vitro and in vivo. The results showed that Specnvezhenide decreases interleukin-1β-induced expression of matix-degrading enzymes and reduces the activation of NF-κB and wnt/β-catenin pathways in vitro. Furthermore, Specnvezhenide treatment prevents the degeneration of both cartilage and subchondral bone in rats OA model. As conclusion, to the best of our knowledge, we report firstly that Specnvezhenide decreases interleukin-1β-induced inflammation on rat chondrocytes by inhibiting activation of NF-κB and wnt/β-catenin pathways, and has therapeutic potential in OA treatment.

Environmental estrogen pollution and estrogen effects on the female reproduction system are well-recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproduction system. 17 β-estradiol is carcinogen and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects the psychological well-being such as depression, fatigue and others. Thus, a simple method of detection of 17 β-estradiol will be important for both environmental estrogen pollution and women’s health care. This study demonstrates a simple-use, cost effective 17 β-estradiol biosensor system which can be used for both environment and women’s health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe (CN) ₆/K₄Fe (CN) ₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER- α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied was between 2.25 pg/mL to 2,250 pg/mL, Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulate urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone which has a similar chemical structure and molecular weight as those of 17 β-estradiol was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

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

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

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19.Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

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

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.

Pyrazinacenes are linearly fused heteroaromatic rings, with N atoms replacing all apical CH moieties. Component rings may exist in a reduced state having NH groups instead of N, causing cross-conjugation. These compounds have interesting optical and electronic properties, including strong fluorescence in the near infrared region and photocatalytic properties, leading to diverse possible applications in bio-imaging, organic synthesis as well as obvious molecular electronic uses. In this study, we have investigated the behaviour of seven-ring pyrazinacene 2,3,11,12-tetraphenyl-7,16-dihydro-1,4,5,6,7,8,9,12,13,14,15,16,17,18-tetradecaazaheptacene (Ph4H2N14HEPT) with emphasis on protic processes including oxidation, tautomerism, deprotonation and protonation, and the species resulting from those processes. We have used computational methods to optimize the structures of the different species and generate/compare molecular orbital structures. Aromaticity of species generated by the different processes has been assessed using the nucleus independent chemical shifts, and trends in the values have been associated with the different transformations of the pyrazinacene core. The computational data was compared with experimental data obtained from synthetic samples of the molecule tBu8Ph4H2N14HEPT.

The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. Yet, several complications were reported, like vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.

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

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

In this paper, we concentrate on the study of the properties of residual Tsallis entropy for order statistics. Order statistics have an important role in reliability structural engineering for example for modelling lifetimes of series and parallel systems. The residual Tsallis entropy of ith order statistic from a continuous distribution function and its deviation from the residual Tsallis entropy of ith order statistics from a uniform distribution is investigated. In a mathematical framework, a method to express the residual Tsallis entropy of the ith order statistic from a continuous distribution in terms of the residual Tsallis entropy of the ith order statistic from a uniform distribution is provided. This approach may provide insight into the behavior and properties of the residual Tsallis entropy for order statistics. Further, we study the monotonicity properties of the residual Tsallis entropy of order statistics under dierent conditions. By studying these properties, deeper understanding of the relationship between the position of order statistics and the resulting residual Tsallis entropy is gained.

Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status and RBC n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 CHD events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for the n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of the marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes, however in the same sample, little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

Li⁺-conducting polyethylene oxide-based membranes, incorporating the N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide, are as electrolyte separators for all-solid-state lithium polymer batteries operating at medium-high temperatures. The incorporation of the ionic liquid remarkably improves the thermal, ion-transport and interfacial properties of the polymer electrolyte, which, in combination with the wide electrochemical stability even at medium-high temperatures, allow high current rates without any appreciable lithium anode degradation. Battery tests carried out at 80 °C have shown excellent cycling performance and capacity retention even at high rates, never tackled by ionic liquid-free polymer electrolytes. No dendrite growth onto the lithium metal anode was observed.

Cassava Solid waste (Onggok) is a solid waste from the cassava-based tapioca industry, the starch content in Onggok is still 50-80 wt.% of residual starch, which can be used to produce maltodextrin for foods application. Furthermore, using cassava solid waste is beneficial in terms of the cost of raw materials. The starch content in cassava can be modified through enzymatic hydrolysis using α-amylase and β-amylase enzymes at 80oC and pH 5.5. Enzymatic hydrolysis was done using mixed enzymes that varied the concentration of α-amylase at 0,.1% and the β-amylase enzymes at 0.05, 0.1, and 0.5%. the concentration of cassava waste (Onggok) varied from 4%, 7%, 10%, and 13%. The optimum concentration of α-amylase and β-amylase enzymes are 0.1% and 0.1% respectively at time intervals of 1 minute resulting in a dextrose equivalent (DE) value 0f 5.7. The characteristics of maltodextrin were studied using scanning electron microscopy (SEM) to determine the morphology of the starch structure which had changed due to the enzyme hydrolysis. Simultaneous thermal analysis (STA) was studied to determine the Thermal stability of hydrolysis products. Maltodextrin produced from cassava waste (Onggok) has a DE value < 10, which has the potential to be used in the pharmaceutical industry

Chrysin, a flavonoid compound, has attracted interest as a therapeutic agent due to its anti-inflammatory, antidiabetic, antidepressant, and particularly its anticancer properties. Although studies have presented findings regarding the anticancer properties of chrysin, research on its molecular mechanisms of action remains largely insufficient. This research aimed to deeply investigate chrysin's effects on the breast cancer cell line, MDA-MB-231, in terms of proliferation, invasion, colony formation, and apoptosis. The XTT test results confirmed chrysin's cytotoxic effect on MDA-MB-231 cells, indicating a 48-hour IC50 value of 115.77 µM. Chrysin induced apoptosis in cells, as evidenced by Annexin V assay, and also reduced their colony-forming and invasion. Gene expression analyses showed elevated levels of APC, AXIN1, AXIN2, GSK3A, GSK3B, CK1α, CTNNB1, as well as apoptosis-related genes CASP3, -7, -9, and BAX. This increase was corroborated by the observed rise in protein levels of caspase 3/7 and GSK3B. Moreover, molecular docking results showed that chrysin interacted with genes in the WNT/β-catenin pathway and exhibited drug-like ADME properties. In conclusion, chrysin exhibits potential anticancer effects against MDA-MB-231 cells. It is hoped that these findings will advance preclinical and clinical studies on chrysin's potential in breast cancer treatment.

Soy isoflavones are considered important sources of bioactive compounds, but they are poorly absorbable, due to their large hydrophilic structures. Some biotransformation strategies have been used to convert the glycosidic form into aglycones, making them available for absorption. This study evaluated the potential of enzymatic and/or microbial fermentation bioprocesses in soymilk extract before and after gastrointestinal in vitro digestion. Commercial β-glucosidase and mix of commercial probiotics containing Lactobacillus acidophilus, L. casei, Lactococcus lactis, Bifidobacterium bifidum e B. lactis were used to biotransform soymilk extract. Isoflavone profile was quantified by HPLC-DAD, total phenolic content by Folin–Ciocalteu test, and antioxidant capacity by ORAC and FRAP. Soymilk enzymatically treated (ET) followed by microbial fermentation (ET+F) resulted in the conversion of glycosylated isoflavones (6-fold lower than control for daidzin and 2-fold for genistin) to aglycones (18-fold greater than control for dadzein and genistein), besides to increase the total phenolic content (3.48 for control and 4.48 mg/ml ET+F) and to improve antioxidant capacity represented by the ORAC (120 for control and 151 mg/ml ET+F) and by the FRAP (285 for control and 317 µl/ml for ET+F) before in vitro digestion. Further, the digested ET+F samples resulted a higher content of genistein (2-fold higher than control) also an increase in the total phenolic content (2.81 for control and 4.03 mg/ml for ET+F) and antioxidant capacity by ORAC were greater compared to undigested samples. In addition, the microbial fermentation process isolated also resulted in the positive effects, but de combination of ET followed by F presented a synergistic effect, suggesting the greater potential for both bioprocesses to contribute to functional and nutritional properties on fermented soy-based products.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

Mushrooms have been an invaluable ingredient in terms of food and medicine to humanity since time immemorial. Mushrooms have been shown to be possessing properties such as anti-tumor, antiproliferative, antioxidant, immunomodulatory, anti-diabetic. Traditional Czech republic medicine involved using Piptoporus betulinus in curing colorectal cancer; similarly, fruiting bodies of Inonotus obliquus were employed in Folk medicine in eastern Europe since the 16^th century. The oriental practice of utilizing mushrooms has witnessed an overwhelming attentiveness from the global research fraternity in exploring its wonder substances. Cancer is one of the key problems faced by researchers in finding an efficient medicine without inducing severe health complications. Mushrooms contain a plethora of bioactive compounds involved in tumor inhibition, such as hispolon, lentinan, gannoderic acid, illudin-s, and many more. The current article briefly describes various edible mushrooms with anti-tumorigenic compounds and their effect on the cancer cells of various means.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease. We aimed to determine the effects of lactoferrin intervention on cognitive function from APP/PS1 mice, and possible mechanisms involved in. Both young and middle-aged male APP/PS1 mice were divided into control and lactoferrin group with 16 weeks’ intervention. Lactoferrin intervention had no effects on cognitive function from both young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered post lactoferrin intervention. In regards to gut microbiota profiles, in the young mice, lactoferrin elevated α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter, in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant post Lf intervention via LEfSe analysis. In the middle-aged mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus and Ruminococcus was significantly reduced post Lf intervention, additionally, S24_7, Bacteroidia, Bacteroidetes and Methylobacterium were specific via LEfSe analysis post lactoferrin intervention. In conclusion, dietary lactoferrin might be beneficial for gut microbiota homeostasis although might have no effects on cognition.

Macro and micronutrients, essential for the maintenance of human metabolism, are daily assimilated through the diet. Wheat and other major cereals are a good source of nutrients, such as carbohydrates and proteins, but cannot supply enough amounts of essential micronutrients which includes provitamin A. As vitamin A deficiency (VAD) lead to several serious diseases spread worldwide, the biofortification of a major staple crop, such as wheat, represents an effective way to preserve human health in developing countries. In the present work, a key enzyme involved in the branch of carotenoids pathway producing β-carotene, lycopene epsilon cyclase, has been targeted by a TILLING approach in a “Block strategy” perspective. The null mutant genotype showed a strong reduction in the expression of lcyE gene and also interesting pleiotropic effects on an enzyme (β-ring hydroxylase) acting downstream in the pathway. Biochemical profiling of carotenoids in the wheat mutant lines showed an increase of roughly 75% in β-carotene in the grains of the complete mutant line vs. the control. In conclusions, here we describe the production and the characterization of a new wheat line biofortified in provitamin A obtained through a non-transgenic approach also shading new light on the molecular mechanism governing carotenoids biosynthesis in durum wheat.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

General phytochemical screening of the aerial parts of Consolida orientalis revealed the presence of steroids, terpenes, phenolic compounds, saponins, fatty acids, alkaloids. This study was conducted to investigate the bioactivities of extracts, isolation and identification the compounds from aerial parts of C.orientalis. The main goal of the present study is identifying and characterizing the antioxidant activity of the Consolida orientalis and biological isolation of active terpenoid. Aerial parts of the plant were dried at room temperature and reduced to small pieces, followed by using extraction with ethyl acetate percolation. Tree complementary analysis system was used, DPPH free radical scavenging test, total phenolic metabolites and FRAP. The total phenolic content was 38.83±2.09 mg gallic acid corresponding to g-1 extract with regarding to standard curve (y=0.0054x+0.0488, r2=0.995). IC50 value for DPPH radical – scavenging was 987.11±28.66 mgml-1. The extract was exhibited a medium reducing power compared with Vit C. The isolation and purification was afforded white crystalline powder which was subjected to physical, chemical and spectral identification by IR, ¹H- and ¹³C- NMR and GC-MS. Isolated compound was identified as β-sitosterol. That is a terpenoid with melting point 133.4-134.5 ͦ c and with molecular formula C₂₉H₅₀O.

The association between depressive symptomatology and cognitive decline has been examined using the Centre for Epidemiologic Studies-Depression Scale (CES-D), however, concerns have been raised about this self-report measure. Here, we examined how the CES-D total score from the 14- and 10-item versions compared to the 20-item version in predicting progression to cognitive decline from a cognitively unimpaired baseline. Data from 1,054 participants were analysed using ordinal logistic regression, alongside moderator and receiver-operating characteristics curve analyses. All baseline total scores significantly predicted progression to cognitive decline. The 14-item version was better than the 20-item version in predicting consensus diagnosis, as shown by their AICs, while also showing the highest accuracy when discriminating between participants by diagnosis at last visit. We did not find sex to moderate the relationship between CES-D score and cognitive decline. Current findings suggest the 10- and 14-item versions of the CES-D are comparable to the 20-item version, and that the 14-item version may be better at predicting longitudinal consensus diagnosis compared to the 20-item version.

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

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

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased transforming growth factor (TGF) β/interferon (IFN)-γ ratio with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4⁺ and CD8⁺ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, Varicella Zoster (VZV) aka Human Herpesvirus 3 (HHV3), HBV, HCV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF-β/IFN-γ and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

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

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

Adequate serum vitamin D and iron levels are thought to positively influence physical training adaptations and mood. The purpose of this prospective, observational, study was to investigate relationships between serum 25-OH vitamin D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (49 female) from 7 indoor and outdoor sports were tested pre-season and post-season for: nutrient biomarkers (serum 25-OH vitamin D and serum ferritin) via venipuncture; body composition (total lean mass, bone mineral densi-ty/BMD, and % body fat) via dual energy x-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female co-horts were combined, significant relationships were noted between pre-season serum 25-OH vit-amin D versus the change (∆: post-season minus pre-season) in both BMD (r=-0.34;p=0.0003) and % body fat (r=-0.28;p=0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r=-0.34;p=0.003). For burnout symptoms, serum 25-OH vitamin D ∆ significantly explained 20.6% of the variance for devaluation of sport in the male cohort only. Across time, serum 25-OH vitamin D levels increased while serum ferritin levels decreased, non-significantly, in both males and fe-males. Relationships between nutrient biomarkers and body composition were opposite of physio-logical expectations.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

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

This study aimed to examine the vitamin D status of professional volleyball athletes and to determine its correlation with shoulder muscle strength. We finally included 52 healthy male professional volleyball players (23.2 ± 4.5 years), who were categorized by vitamin D status (<20 ng/mL: deficiency, 20-30 ng/mL: insufficiency, and >30 ng/mL: sufficiency). We examined the strength of the internal rotator (IR) and external rotator (ER) muscles of the shoulder by using isokinetic dynamometer. Fourteen players (26.9%) had vitamin D deficiency, 24 players (46.2%) were vitamin D insufficient, and 14 players (26.9%) were vitamin D sufficient. There was no significant correlation between the vitamin D level and shoulder muscle strength at 60°/s (IR, r = 0.159, p = 0.26; ER, r = 0.245, p = 0.08), and at 180°/s (IR, r = - 0.093, p = 0.51; ER, r = - 0.037, p = 0.79). Moreover, the isokinetic shoulder strengths were not significantly different across the three groups in all settings. In conclusion, vitamin D insufficiency was common in elite volleyball players. Though not being associated with isokinetic muscle weakness, vitamin D should be regularly monitored and supplemented in young elite athletes, considering its importance on musculoskeletal health.

Since it was proposed, the Robot Operating System (ROS) has fostered solutions for various problems in robotics in the form of ROS packages. One of these problems is Simultaneous Localization and Mapping (SLAM), a problem solved by computing the robot pose and a map of its environment of operation at the same time. The increasingly availability of robot kits ready to be programmed and also of RGB-D sensors often pose the question of which SLAM package should be used given the application requirements. When the SLAM subsystem must deliver estimates for robot navigation, as is the case of applications involving autonomous navigation, this question is even more relevant. This work introduces an experimental analysis of GMapping and RTAB-Map, two ROS compatible SLAM packages, regarding their SLAM accuracy, quality of produced maps and use of produced maps in navigation tasks. Our analysis aims ground robots equipped with RGB-D sensors for indoor environments and is supported by experiments conducted on datasets from simulation, benchmarks and from our own robot.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

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.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p&lt; 0.0001) and NAC+Pb groups (p&lt;0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Thus, this study evaluated the anti-inflammatory potential of the compound N'-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. To find out the likely mechanism of action, a preliminary molecular docking study was performed focusing on the crystallographic structures of NFκB, iNOS, and sGCs. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the control group, with the 10 mg/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-α, IL-17, and IFN-γ, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-α levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.

The objective of this work was to investigate the effect of different soil tillage practices in sunflower cultivation in a rotation system with intercropping Triticosecale x Pisum sativum. For this purpose a two year experimental field of 5% slope was established in central Greece. There were four treatments with three replications each. The treatments were: (a) no tillage - planting parallel to the contour (NTC-PAC), (b) conventional tillage - planting parallel to the contour (CTC-PAC), (c) no tillage - planting perpendicular to the contour (NTC-PEC), (d) conventional tillage - planting perpendicular to the contour (CTC-PEC). During the experiment plant height, leaf area index, specific leaf area, plants’ total nitrogen and plants’ proteins were measured. According to the results plant height ranged from 64.9 (CTC-PAC) to 85.2 cm (NTC-PEC) the 1st year and between 66.5 – 86.5 cm in CTC-PAC and NTC-PEC treatments in the 2nd year. Furthermore, LAI and SLA, plant’s total nitrogen and protein content and N-uptake were affected positively by the no tillage practice. To conclude, sunflower is a promising crop in a rotation system with intercropping Triticosecale x Pisum sativum, cultivating under rainfed sloping conditions.

Inappropriate use of fertilizers is one of the major production constraints in sesame. Studies to optimize the use of N fertilizer on sesame were conducted at Humera Agricultural Research Center (HuARC) under rain fed and irrigation conditions. Thirteen (13) N doses were evaluated in a Randomized Complete Block Design (RCBD) during 2016, 2017 and 2018. In the rain fed condition; results showed higher number of days to 50% flowering on the higher N application. The 31-121.5 kg N ha-1 have scored higher seed yield, where the lower (18 kg N ha-1) and higher (156 kg N ha-1) N doses scored lower seed yield. In the irrigation condition; higher N application rate prolonged the flowering time to some extent and days to 90% maturity was reduced as N rate increased. Heavier seed weights and maximum seed yield were recorded on 64 and 75 kg N ha-1 and the lower N doses scored low seed yield. Agronomic efficiency of N fertilizer (N-AE) was higher on 64 kg N ha-1 under both growing conditions. The partial budget analysis revealed that 64 kg N ha-1 (rain fed) and 75 kg N ha-1 (irrigation) had the higher net profit, MRR and residual ranking. Therefore, for the greater sesame productivity 64 kg N ha-1 has to be recommended for rain fed and 64 to 75 kg N ha-1 for the irrigated sesame.

In no-tillage systems, there is an accumulation of crop residues (CR) which plays an important role in available of soil-N. A study was set up to provide information regarding the CR N credit, and the influence of N mineral fertilizer. An incubation was run in a loam soil with addition of a similar rate of residue (10 Mg ha-1; sugarcane, soybean, and brachiaria) and N mineral fertilizer (urea; 120 kg N ha-1). After the stabilization of biological activity, soil and remaining residues were collected, and N monitored. Results showed that the N credit was positive with application of soybean, sugarcane, and brachiaria. There was an expressive performance of soybean N credit represented by a positive balance, and a reduction from 2.49 to 0.9 g kg-1 of N in residue, with direct increase of 90% of soil-N. There is no need of N fertilizer to potentialize the soybean N credit, but it is requested to potentialize N credit of brachiaria and sugarcane. The urea demonstrated be a good enhancer of brachiaria N credit, but it was not adequate to sugarcane residues. Based in our result, the accumulation and incorporation of CR can be considered as a N credit with positive contribution in soil-N.

The high interest in N-heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. They displayed an effective activity after only 45 minutes of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives.

Researches on flexible thermoelectric (TE) materials usually focus on conducting polymers (CPs) and CP-based composites; however, it is a great challenge to obtain high TE properties comparable to inorganic counterparts. Here, we report an n-type Ag₂Se film on flexible nylon membrane with an ultrahigh power factor ~987.4 ± 104.1 μWm⁻¹K⁻² at 300 K and an excellent flexibility (93% of the original electrical conductivity retention after 1000 bending cycles around a 8-mm diameter rod). The flexibility is attributed to a synergetic effect of the nylon membrane and the Ag₂Se film intertwined with numerous high-aspect-ratio Ag₂Se grains. A TE prototype composed of 4-leg of the hybrid film generates a voltage and a maximum power of 19 mV and 460 nW, respectively, at a temperature difference of 30 K. This work opens opportunities of searching for high performance TE film for flexible TE devices.

In this work the influence of the structure forming agent on the composition, morphology and oxygen reduction reaction (ORR) activity of Fe-N-C catalysts was investigated. As structure forming agent (SFA), dicyandiamide (DCDA) (nitrogen source) or oxalic acid (oxygen source) or mixtures thereof were used. For characterization, cyclic voltammetry and rotating disc electrode (RDE) experiments were performed in 0.1 M H2SO4. In addition to this, N2 sorption measurements and Raman spectroscopy were performed for the structural characterization. The role of metal, nitrogen and carbon sources within the synthesis of Fe-N-C catalysts has been pointed out before. Here, we show that the optimum in terms of ORR activity is achieved if both N- and O-containing SFAs are used in almost similar fractions. All catalysts display a redox couple, whereat its position depends on the fractions of SFAs. The SFA has also a strong impact on the morphology: Catalysts that were prepared with a larger fraction of N-containing SFA revealed a higher order in graphitization, indicated by bands in the 2nd order range of the Raman spectra. Nevertheless, the optimum in terms of ORR activity is obtained for the catalyst with highest D/G band ratio. Therefore, the results indicate that the presence of an additional oxygen-containing SFA is beneficial within the preparation.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

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

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of &gt;90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of &lt;80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

The purpose of this study was to investigate the effect of circuit training on β-amyloid, BDNF, and cognitive function in untrained obese elderly Korean women. The subjects for the study were aged 65–70 years, composed of the circuit training group(n=12) and control group(n=11). The 60-minute combined exercise was performed 3 times per week for 16 weeks. Exercise intensity was progressively increased from 40% HRR to 70% HRR. The test data were analyzed by paired t-test, independent t-test, and two-way repeated measures ANOVA, and the alpha level of .05 was set for all tests of significance. The findings of this study were as follows: β-amyloid significantly decreased after the exercise group had compared to before the exercise and BDNF and cognitive function significantly increased after the exercise group had compared to before the exercise. However, there were no significant changes in β-amyloid, BDNF, and cognitive function in the control group Therefore, it is suggested that the circuit training used in this study could be an effective exercise method for improving the risk factors of cognitive impairment in obese elderly Korean women.

The significant environmental issue of water pollution caused by emerging contaminants un-derscores the imperative for developing novel cleanup methods that are efficient, economically viable, and that are intended to operate at high capacity and under continuous flows at the in-dustrial scale. This study shows the results of the operational design to build a prototype for the retention at lab scale of pollutants residues in water by using as adsorbent material, insoluble polymers prepared by β-cyclodextrin and epichlorohydrin as a cross-linking agent. Laboratory in batch tests were run to find out the adsorbent performances against furosemide and hydro-chlorothiazide as pollutants model. The initial evaluation concerning the dosage of adsorbent, pH levels, agitation, and the concentration of pharmaceutical pollutants enabled us to identify the optimal conditions for conducting the subsequent experiments. The adsorption kinetic and the mechanisms involved were evaluated revealing that that the experimental data perfectly fit the pseudo second order model being the adsorption process mainly governed by chemisorption. According to the KF constants values of 0.044 (L/g) and 0.029 (L/g) for furosemide and hydro-chlorothiazide, respectively and determination coefficient (R2) higher than 0.9 for both com-pounds, Freundlich yielded the most favorable outcomes, suggesting that the adsorption process occurs on heterogeneous surfaces involving both chemisorption and physisorption processes. The maximum monolayer adsorption capacity (qmax) obtained by Langmuir isotherm reveal a saturation of the β-CDs-EPI polymer surface 1.45 times higher for furosemide (qmax = 1.282 mg/g) than hydrochlorothiazide (qmax = 0.844 mg/g). Based on these results, the sizing design and building of a lab scale model were conducted, which in turn will be used later to evaluate its performances working in continuous flow in a real scenario.

The heterogeneous nature of human breast cancer (HBC) can still lead to therapy inefficacy and high le-thality and new therapeutics are needed as well as new spontaneous animal models to benefit translational HBC research. Dogs are primarily investigated since they spontaneously develop tumors which share many features with human cancers. In recent years, different natural phytochemicals including berberine, a plant alkaloid, have been reported to have antiproliferative activity in vitro in human cancers and in rodent animal models. In this study, we report the antiproliferative activity and mechanism of action of berberine, of its active metabolite berberrubine, and of eight analogues, on a canine mammary carcinoma cell line and in transgenic zebrafish models. We demonstrate both in vitro and in vivo the significant effects of specific analogues on cell viability, via induction of apoptosis, also identifying their role in inhibiting the Wnt/β-catenin pathway and activating the Hippo signals with a downstream reduction of CTGF expres-sion. Particularly the berberine analogues NAX035 and NAX057 show the highest therapeutic efficacy, de-serving further analyses to elucidate their mechanism of action more in detail, and in vivo studies on spon-taneous neoplastic diseases aiming at improving veterinary treatments of cancer as well as translational cancer research.

Background In many African countries, clinical samples are not routinely tested for carbapenem-resistant bacteria, the resistance data remaining limited. Material and methods In March 2020 –June 2022, we collected extended spectrum β-lactamase (ESBL) -producing Enterobacterales (ESBL-PE) isolates from five hospitals in Burkina Faso. The species were identified using API20E and ESBL production confirmed by double-disc synergy test. Production of carbapenemases and AmpC-β-lactamases and phenotypic co-resistance were determined. Results Among the 473 ESBL-PE, 356 were ESBL- E. coli (ESBL-Ec) and 117 Klebsiella spp. (ESBL-K). Of the isolates, 5.3% were carbapenemase and 5.3% AmpC-β-lactamase positive Three types of carbapenemases were identified: 19 NDM, 3 OXA-48 like and 1 VIM. Two isolates produced both NDM and OXA48-like carbapenemases. Carbapenemase rates were highest among isolates in tertiary hospitals. Co-resistance rates were up to 85% for aminoglycosides, 90% for sulfonamides, 95% for fluoroquinolones and 25% for chloramphenicol, Fosfomycin resistance was 6% for ESBL-Ec and 49% for ESBL-K (49%). Conclusion Many ESBL-Ec and ESBL-K co-produced carbapenemases and/or AmpC-β-lactamases, at all healthcare levels and in various samples, with high co-resistance rates to non-betalactams. Carbapenem resistance is no longer rare, calling for testing in routine diagnostics, vigorous resistance surveillance system, and infection control within healthcare.

The aim of this study is to prepare redox-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via disulfide bond creating nanophotosensitizers that were fabricated for redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize suc-cinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss) and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). Chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by dialysis procedure. They formed small particles with an average particle size of 152.0±23.2 nm and they showed improved singlet oxygen (SO) generation in the aqueous solution under light irradiation and was significantly higher than that of Ce6 alone. Ce6 release rate from bCDsu-ss-Ce6 nanophotosensitizers was accelerated by addition of glutathione (GSH), indicating that bCDsu-ss-Ce6 nanophotosensitizers have re-dox-sensitive photosensitizer delivery capacity. bCDsu-ss-Ce6 nanophotosensitizers have low in-trinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, bCDsu-ss-Ce6 nanophotosensitizers showed improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production and phototoxicity compared to those of Ce6 alone. GSH addition resulted in higher Ce6 uptake ratio, ROS generation and phototoxicity than those of Ce6 alone, indicating that bCDsu-ss-Ce6 nanophotosensitizers have redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. At tumor xenograft model using HeLa cells, bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than normal organs, i.e. fluores-cence intensity in tumor tissues was significantly higher than those of other organs while Ce6 alone did not specifically target tumor tissue. These results indicated higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, by efficiently inhibiting growth of tumor in in vivo animal tumor xenograft study.

The β-thalassemias are hereditary monogenic diseases characterized by low or absent production of adult hemoglobin and excess in the content of α-globin. This excess is cytotoxic for the erythroid cells and responsible of the β-thalassemia associated ineffective erythropoiesis. Therefore, the decrease of α-globin excess is a relevant clinical effect for these patients and can be obtained by induction of fetal hemoglobin, by autophagy, or both. The in vivo effects of sirolimus (rapamycin) and analogues on induction of fetal hemoglobin (HbF) is of key importance for therapeutic protocols in a variety of hemoglobinopathies, including β-thalassemia. In this research communication, we report data showing that decrease of autophagy-associated p62 protein, increased expression of ULK-1 and reduction of the excess of α-globin is operating in erythroid precursors (ErPCs) stimulated in vitro with low dosages of sirolimus. In addition, increased ULK-1 mRNA content and decrease of α-globin content were found in ErPCs isolated from β-thalassemia patients recruited for the NCT03877809 clinical trial and treated with 0.5-2 mg/day sirolimus. Our data support the concept that autophagy, ULK1 expression and α-globin chain reduction should be considered important endpoints in sirolimus-based clinical trials for β-thalassemia.

The aim of this systematic review is to describe and to identify prospect of β-Tricalcium Phosphate (β-TCP) as Alveolar Bone Grafting (ABG) in Cleft Lip/Palate (CL/P) or alveolar bone cleft defect. A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted with MEDLINE/PubMed, Web of Science/ ISI-Web of Knowledge, Scopus and Cochrane Library with English language and no publication year limits. The keywords yielded a total of 5824 publications. There are 3196 suitable articles to evaluate after removing duplicates and languages. Afterward, 1315 studies left after doing title and abstract reading. In addition, 85 full-articles were assessed for eligibility. The read the complete texts of those papers and eventually chose 20 that matched the inclusion requirements. Thirteen of the twenty studies included in this systematic review had a low risk of bias, one had a high risk of bias, and six had moderate bias which not report the randomization. β-TCP as ABG is biocompatible, visible and practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. β-TCP as synthetic ABG can be the alternative to autologous bone grafts with several terms and conditions. Improvement of β-TCP efficacy for ABG in CL/P or alveolar bone cleft defects can be done by a tissue engineering approach combining β-TCP with growth factor, mesenchymal stem cells, or other graft materials and modification of β-TCP physical properties.

Background: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of β -Lapachone, a novel synthetic compound. Methods: The antibacterial activity of the β -Lapachone compound was examined against laboratory strains by agar well diffusion method, minimal inhibitory concentration (MICs), and minimal bactericidal concentration (MBCs). Growth kinetics inhibition in presence of β -Lapachone on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa (ATCC 27853) was assessed by MABA. Crystal violet blue assay was used for biofilm inhibition assays, biofilm eradication assay and for molecular modeling PyMOL was used. Results: β -Lapachone exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Molecular modeling predicted the binding of β -Lap at active site and heme binding site of catalase, KatA. The activity of some commercial antibiotics was enhanced in association with β -Lap. In addition, β -Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains.

Klebsiella pneumoniae (Kp) has gained prominence in the last two decades due to its global spread as a multi-drug resistant (MDR) pathogen. Further, Carbapenem-Resistant Kp are emerging at an alarming rate. The objective of this study was (1) to evaluate the prevalence of β-lactamases, especially carbapenemases in Kp isolates from India, (2) determine the most prevalent sequence type (ST) & plasmids, and their association with β-lactamases. Clinical samples of K. pneumoniae (n=65) were collected from various pathology lab, drug susceptibility and minimum inhibitory concentrations (MIC) were detected. Whole genome sequencing (WGS) was done for (n=22) resistant isolates and WGS analysis was performed using various bioinformatics tools. Additional Indian MDR Kp genomes (n=187) were retrieved using Pathosystems Resource Integration Center (PATRIC) database. Detection of β-lactamase genes, location, plasmid replicons, and ST type of genomes were carried out using CARD, mlplasmids, PlasmidFinder, and PubMLST respectively. All data were analyzed and summarized using iTOL tool. ST231 was highest, followed by ST147, ST2096 & ST14 among Indian isolates. blaAmpH was detected as the most prevalent gene followed by blaCTX-M-15, blaTEM-1. Among carbapenemase genes, blaOXA-232 was prevalent and associated with ST231, ST2096 and ST14, which was followed by blaNDM-5 which was observed to prevalent in ST147, ST395 &ST437. ST231 genomes were most commonly found to carry Col440I and ColKP3 plasmids. ST16 carried mainly ColKP3, and Col (BS512) was abundantly present in ST147 genomes. One Kp isolate with novel MLST profile was identified, which carried blaCTX-M-15, blaOXA-1 and blaTEM-1. ST16 &ST14 from this study, which is mostly dual producer of carbapenem and ESBL genes, could be emerging high-risk clones in India.

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagen-fibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties.

β-Ga2O3 crystal have attracted great attentions in the fields of photonics and photoelectronics because of its ultra wide-band gap and high thermal conductivity. Here, pure β-Ga2O3 crystal was successfully grown by optical floating zone (OFZ) method, and used as saturable absorbers to realize a passively Q-switched all-solid-state 1μm laser for the first time. By placing the as-grown β-Ga2O3 crystal into the resonator of Nd:GYAP solid-state laser, a Q-switched pulses at the center wavelength of 1080.4 nm are generated under a output coupling of 10%. The maximum output power is 191.5 mW while the shortest pulse width is 606.54 ns, and the maximum repetition frequency is 344.06 kHz. The maximum pulse energy and peak power are 0.567 μJ and 0.93 W, respectively. Our experimental results show that β-Ga2O3 crystal has great potential in the development of all-solid-state 1μm pulsed laser.

β-cyclodextrin-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, we synthesized well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) acted as theranostic nanoparticles for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX) and superparamagnetic iron oxide particles (SPIO) were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to folate receptor-mediated endocytosis process of the nanoparticles and GSH triggered disulfide-bonds cleaving.Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO showed strong MRI contrast enhancement properties. In conclusion, folate-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjӧgren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS, although TGFβ family members seems to have ambiguous effects on the function of pSS salivary glands. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

In this paper, the lamellar structural evolution and microvoids variations of β-iPP during the processing of two different stretching methods, sequential biaxial stretching and simultaneous biaxial stretching, were investigated in detail. It was found that different stretching methods led to significantly different lamellae deformation modes, and the microporous membranes obtained from the simultaneous biaxial stretching exhibited better mechanical properties. For the sequential biaxial stretching, abundant coarse fibers originated from the tight accumulation of the lamellae parallel to the longitudinal stretching direction, whereas the lamellae perpendicular to the stretching direction were easily deformed and separated. Those coarse fibers were difficult to be separated to form micropores during the subsequent transverse stretching process, resulting in a poor micropores distribution. However, for the simultaneous biaxial stretching, the β crystal had the same deformation mode, that is, the lamellae distributed in different directions were all destroyed, forming abundant microvoids and little coarse fibers formation.

COVID-19 disease, caused by the SARS-CoV2 virus, is a potentially fatal disease that represents a serious public health and economic problem worldwide. The SARS-CoV2 virus infects the lower respiratory tract and can cause pneumonia in humans. ARDS is the leading cause of death in COVID-19 disease. One of the main characteristics of ARDS is the cytokine storm, an uncontrolled systemic inflammatory response resulting from the release of pro-inflammatory cytokines and chemokines and growth factors, by immune cells. The other important aspect of the disease is represented by the involvement of the vascular organ that undergoes endothelitis. Hyperinflammation and endothelitis contribute in various ways to trigger coagulation disorders with diffuse micro thrombotic and thromboembolic phenomena. Lastly, multiple organ failure may occur (MOF). Since so far there is no approved treatment, there is an urgent need to reposition known treatments, considered safe, to be included in trials. Naturally produced interferons represent the body's first line of defense against viruses. Pharmacological forms, obtained by means of genetic recombination techniques, have long been approved and used to treat numerous pathologies. Interferons are divided into three families, within which some subfamilies are distinguishable. Only IFN-II comprises a single isoform which has completely different aspects and functions. The IFN I and III, however, each comprise different subfamilies (17 subfamilies the IFN-I and 4 subfamilies the IFN-III), share many aspects, representing the body's first antiviral response, but play different roles. The use of IFNs has been studied in two severe hCoV (Human Coronavirus) diseases, closely related to COVID-19 disease, such as SARS and MERS. Numerous in vitro and in vivo studies have been conducted, often in combination with other antivirals. The results have been controversial. The positive results in vitro and in experimental animals were often not replicable in humans. The possible positioning of these molecules in the right window of therapeutic opportunity requires that the complex dialogue between IFN, inflammasome, cytokines, pro-inflammatory chemokines, growth factors and barrier function be shed light.

A derivative series of 3,4-dimethoxy-β-nitrostyrene were synthesized and identified including new compound 6. The effect of antimicrobial activity of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking was also performed to obtain information about their interactions with Protein Tyrosine Phosphatase 1B (PTP1B). PTP1B containing cysteine 215 and arginine 221 as essential active residues plays a key role in signaling pathways that regulate various cell functions of microorganisms, which also act as negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. Compound 5 and 6 were the most potent as fragment of PTP1B inhibitor based on molecular docking, but compound 5 was more effective against Candida albicans. These compounds interact with serine 216 and arginine 221 residues. However, further research is needed to investigate their potential medicinal use.

Thienopyrimidines are a versatile group of compounds that contain a biologically active pharmacophore and reported to have anticancer efficacy in vitro. Here, we report for the first time, that thieno[3,2-d]pyrimidine - based compounds, designated the RP series, have efficacy in prostate cancer cells. The lead compound, RP-010, was efficacious in PC3 and DU-145 prostate cancer (PC) cells (IC50< 1µM). The cytotoxicity of RP-010 was significantly lower in normal cells. RP-010 (0.5, 1, 2, and 4 µM) arrested prostate cancer cells in the G2 phase of the cell cycle, induced mitotic catastrophe and apoptotic signaling in both PC cell lines. Mechanistic studies suggested that RP-010 (1 and 2 µM) inhibits the wingless-type MMTV (Wnt)/β-catenin signaling pathway, mainly by inducing β-catenin fragmentation, while down regulating important proteins in the pathway, i.e. LRP-6, DVL3, and c-Myc. Interestingly, RP-010 (1 and 2 µM) induced the nuclear translocation of the negative feedback proteins, Naked 1 and Naked 2, in the signaling pathway. In addition, RP-010 (0.5, 1, 2, and 4 µM) significantly decreased the migration and invasiveness of PC cells in vitro. Finally, RP-010 did not produce significant toxic effects in zebrafish at concentrations up to 6 µM. In conclusion, RP-10 is a promising anticancer compound in metastatic prostate cancer and did not produce overt toxicity in an in vivo zebrafish model. Future mechanistic and efficacy studies are needed in-vivo to optimize the lead compound RP-010 for clinical use.

Recent interest in intestinal hormones has risen with the idea that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones like peptide YY (PYY), ghrelin, glucagon-like peptide (GLP)-1 and 2, and cholecystokinin (CKK) are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Furthermore, in the recent years, multiple studies suggest that the microbiota is critically important for normal host functions, while impaired host microbiota interactions contribute to the pathogenesis of numerous common metabolic disorders. In this study, we considered the nutraceutical effects of β-glucans added to pasta at the concentration of 6g\100g. Ten participants have been recruited and hematochemical analyses and intestinal hormones tests have been performed before and after 30 days of pasta intake. Stool specimens have been studied for Lactobacillus Fermentum, Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium longum, and Enterococcus faecium presence before and after 30 days of nutritional intervention. After 30 days of regular intake of pasta enriched by β-glucans results have been evaluated. In conclusion, pasta prepared from barley flour enriched with β-glucans at 6% exhibit promising responses on glucose metabolism, on intestinal hormones responses and on microbiota modification.

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

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

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

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

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

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

Revenue-sharing (RS) contracts are a common approach to incentivize innovation of upstream suppliers by addressing the uneven profit distribution between upstream and downstream firms. Considering the possible overconfidence characterizing decision makers in the supply chain, we investigate the effect of the RS contract and the tendency of overconfidence of supply chain members on the investment in R&D of key components of products in the context of an upstream supplier that is the leader in the R&D and production of key components. We find that regardless of the bargaining power of either party, a RS contract can increase the R&D investment in key components. Regarding the effects of overconfidence of either downstream manufacturer or up-stream supplier, it can increase the R&D investment in key components. Supplier (manufacturer) overconfidence can harm their own profits but increase the profits of the manufacturer (supplier), and when the level of overconfidence is below a certain threshold, the damage to their own profits is less than the increase in each other's profits, thus benefiting the whole supply chain. In addition, we also find a joint effect of RS contracts and overconfidence: when the bargaining power of the supplier is low, the RS contract has a certain compensatory effect on the loss of their own profits caused by overconfidence.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

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

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

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

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