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

Octacalcium phosphate (OCP) is a precursor of biological apatite crystals that has attracted attention as a possible bone substitute. On the other hand, few studies have examined this material at the experimental level due to the limitations of OCP mass production. Recently, mass production technology of OCP was developed, and the launch of OCP bone substitutes is occurring. In this study, the bone regeneration capacity of OCP products was compared with two of the most clinically used materials: heat-treated bovine bone (BHA) and sintered biphasic calcium phosphate (BCP). Twelve rabbits were used, and defects in each tibia were filled with OCP, BHA, BCP, and left unfilled as control (CON). The tibias were harvested at 4 and 12 weeks, and 15 μm slides were prepared using the diamond grinding method after being embedded in resin. Histological and histomorphometric analyses were performed to evaluate the bone regeneration ability and mechanism. The OCP showed significantly higher resorption and new bone formation in both periods analysed (p<0.05). Overall, OCP bone substitutes can enhance bone regeneration significantly by activating osteoblasts and a rapid phase transition of OCP crystals to biological apatite crystals (mineralisation), as well as providing additional space for new bone formation by rapid resorption.

Electricity demand forecasting has been a real challenge for power system scheduling in the different levels of the energy sectors. Various computational intelligence techniques and methodologies have been employed in the electricity market for load forecasting; although, scant evidence is available about the feasibility of each of these methods considering the type of data and other potential factors. This work introduces several scientific, technical rationale behind intelligent forecasting methods, based on the work of previous researchers in the field of energy. The fundamental benefits and main drawbacks of the aforementioned methods are discussed in order to depict the efficiency of each approach in various situations. In the end, a proposed hybrid strategy is represented.

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

Abstract: Turmeric is a plant with multiple medicinal attributes. One of them being its analgesic effect. In this project the analgesic effect of the plant was evaluated with an inflammatory pain model: the 5% formalin model. Turmeric was administered to 250 g male Wistar rats (6 ± 2) provided by the Health Science department’s vivarium. The dose-response curve of the plant was per-formed observing the analgesic effect. Once the dose was selected, they were administrated within different turmeric protocols. 400 mg orally every 24 h for two weeks, another group with turmeric ad libitum for two weeks, the control group with 0.9% saline solution for two weeks, and a group with administration of metamizole prior to evaluation with 5% formalin. Subsequently, each rat was evaluated by 5% formalin intraplantarly and the number of rat paw twitches per 1 h was observed. The analysis of the data generated through the obtained results was carried out. The dose of 400 mg of oral turmeric was administered for two weeks without observing any collateral effects. An excellent analgesic effect was found in this protocol, as well as, in the ad libitum administration for two weeks compared to the control group. Likewise, turmeric presents a milder effect than metamizole, a well-known analgesic.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The study subjects were 158 patients (68 males and 90 females, mean age 74.8±11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e’ and E/e’ (p<0.001, respectively). Multivariate logistic regression analysis revealed that PWV higher values and hypertension were significant predictors for the dependent factor (HFpEF). Conclusions: Arterial stiffness amplified LV afterload, leading to LV concentric hypertrophy and LV diastolic dysfunction. This study presents that arterial stiffness due to phosphate retention, and hypertension are important predictors of HFpEF.

The collapsible loess will rapidly soften and lose its bearing capacity when soaked in water. Under a mild condition (20°C), the biomimetic inorganic agent, Diammonium phosphate (DAP), reacts with calcite in the collapsible loess, producing a stronger bonding material, hydroxyapatite (HAP), to modify and stabilize the soil. Uniaxial compression, permeability tests and morphological analysis using XRD and SEM/EDX microscopy were carried out to assess the effectiveness of DAP stabilization on the collapsible loess. The results indicated that HAP improved the inter-particle bonding within loess, filled the pores within particles, reduced the permeability, and consequently mitigated collapsibility of loess. The compressive strength of DAP-treated loess increased as DAP concentration increased. Following 28-days curing, the compressive strength of the loess treated with a 3.0 mol/L DAP solution was six times greater than that of the untreated group. DAP's reinforcement effect on loess was superior to that of cement. The compressive strength of DAP-treated loess was about double that of cement-treated loess and the permeability coefficient was reduced by more than 50% at equivalent solid content. Furthermore, DAP generated 68% fewer carbon emissions compared to Portland cement. Considering eco-friendly and sustainable development, DAP offers a more competitive alternative for modification and stabilization of loess.

Candidatus Accumulibacter belongs to phosphate-accumulating organisms (PAO) which exhibit cyclic metabolism and are capable of intracellular polyphosphate accumulation and their hydrolysis under feast-famine anaerobic-aerobic cycling. In consortia of activated sludge microorganisms, these bacteria are responsible for enhanced biological phosphorus removal (EBPR). The spectrum of the substrates used by Ca. Accumulibacter remains insufficiently studied. It was investigated by measuring the oxygen uptake rates (OUR) of Ca. Accumulibacter-enriched culture supplemented with 17 different organic substrates. The highest oxygen uptake rates values were observed in the presence of tryptone, volatile fatty acids (acetate, propionate, and butyrate), succinate, pyruvate, and amino acids (aspartate and glutamate). Phosphate dynamics in the medium under shifts from anaerobic to aerobic cultivation in batch experiments was studied for these compounds (except for tryptone). All tested substrates were shown to cause phosphate cycling (release in the anaerobic phase and uptake in the aerobic one), with OURs for the substrates correlating with the amount of phosphates consumed during the aerobic phase. It was concluded that OUR may be used as an indicator of the monosubstrates used by Ca. Accumulibacter in the anaerobic/aerobic cycle. The possible pathways for substrate transport and metabolism by Ca. Accumulibacter are discussed using the stoichiometric data and the results of metagenomic analysis.

Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in bone regeneration. iTRAQ generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity. We propose DPSCs as a suitable MSCs for bone regeneration cell-based strategies.What do you want to do ?New mailCopy

3D plotting is an additive manufacturing technology enabling biofabrication, thus the integration of cells or biologically sensitive proteins or growth factors into the manufacturing process. However, most (bio-)inks developed for 3D plotting were not shown to be processed into clinical relevant geometries comprising critical overhangs and cavities, which would collapse without a sufficient support material. Herein, we have developed a support hydrogel ink based on methylcellulose (mc), which is able to act as support as long as the co-plotted main structure is not stable. Therefore, 6 w/v %, 8 w/v % and 10 w/v % mc were allowed to swell in water, resulting in viscous inks, which were characterized for their rheological and extrusion properties. The successful usage of 10 w/v % mc as support ink was proven by multichannel plotting of the support together with a plottable calcium phosphate cement (CPC) acting as main structure. CPC scaffolds displaying critical overhangs or a large central cavity could be plotted accurately with the newly developed mc support ink. The dissolution properties of mc allowed complete removal of the gel without residuals, once CPC setting was finished. Finally, we fabricated a scaphoid bone model by computed tomography data acquisition and co-extrusion of CPC and the mc support hydrogel.

The pentose phosphate pathway (PPP) is one of three major pathways involved in glucose metabolism, regulated by glucose-6-phosphate dehydrogenase (G6PD), controlling NADPH formation. NADPH, in turn, regulates the balance of oxidative stress and reactive oxygen species (ROS) levels. G6PD dysfunction, affecting PPP, is implicated in neurological disorders, including epilepsy. However, PPP's role in epileptogenesis and ROS production during epileptic activity remains unclear. To clarify these points, we conducted electrophysiological and imaging analyses on mouse hippocampal brain slices. Using the specific G6PD inhibitor G6PDi-1, we assessed its effects on mouse hippocampal slices, examining intracellular ROS, glucose/oxygen consumption, and ROS production during synaptic stimulation and in the 4AP epilepsy model. G6PDi-1 increased basal intracellular ROS levels and reduced synaptically induced glucose consumption but had no impact on ROS production from synaptic stimulation. In the 4AP model, G6PDi-1 didn't significantly alter spontaneous seizure frequency or H2O2 release amplitude but increased the frequency and peak amplitude of interictal events. These findings suggest that short-term PPP inhibition has a minimal impact on synaptic circuit activity.

Despite significant research efforts, the question of whether rising atmospheric CO₂ concentrations (C_a) affect leaf respiration remains unanswered. Here, I reanalyse published hydrogen isotope abundances in starch glucose of sunflower leaves. I report that, as C_a increases from 450 to 1500 ppm, respiration by the oxidative pentose phosphate pathway in chloroplasts increases from 0 to ≈ 5% relative to net carbon assimilation. This is consistent with known regulatory properties of the pathway. Summarising recent reports of metabolic fluxes in plant leaves, a picture emerges in which mitochondrial processes are distinctly less important for overall respiration than the oxidative pentose phosphate pathways in chloroplasts and the cytosol. Regulatory properties of these pathways are consistent with observations of lower-than-expected stimulations of photosynthesis in response to increasing C_a. Reported advances in understanding leaf respiratory mechanisms may enable modelling and prediction of respiration effects (inter alia) on biosphere-atmosphere CO₂ exchange and plant performance under climate change.

Alzheimer's disease (AD) is characterized by abnormal amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-PET or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for non-invasive and cost-effective detection of brain Aβ accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aβ42/Aβ40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n=88) and some volunteers (n=66) were subject to evaluation of amyloid status by CSF Aβ quantification or PET analysis. Thresholds of plasma Aβ42/Aβ40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

Load shifting is one of the demand side management (DSM) strategies to support the efficiency in the electricity grid during the peak hours demand. Load shifting at the appliance level is interesting to review since the appliance usage is one of the main inputs in the load profile analysis. More review studies in load shifting at the appliance level are required as it is a specific issue of load profile research body, and still limited studies are available at this moment. It is also essential to focus on the appliance usage patterns to better understand the impacts and characteristics of the individual appliance. The existing studies in load shifting have applied common structured literature reviews, and our study addresses the transparency of each stage and sub-stage of the selection of the final list studies. The finding shows that efficiency has been achieved in the installed capacity reduction, cost including emission reductions, and peak consumption reduction. The most applied method in the load shifting at the appliance level is by developing the load shifting optimisation algorithms. This work contributes to provide a transparent process of applying a systematicity literature review, where it becomes a source of knowledge and grounded theory. It contributes to a limited and specific research of load shifting at the appliance level by highlighting and discussing the key findings for the readers. In specific, it contributes to improve energy efficiency by presenting the load shifting methods at the appliance level and identifying the controllable and uncontrollable appliances. This detail review study at the appliance level can make valuable contributions to support decision and policy-making by illuminating new dynamic system in load shifting area in specific, and demand side management in general for energy efficiency.

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

In this paper I will address Dr. Sonne’s questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas and is more immature and more symptomatic while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions that Dr. Sonne presented and will discuss also my published theory on the physical nature of subjective experience and its relation to the brain and how that theory interacts with DBP, and how the 2 theories relate to subjective experience, will, behavior, psychopathology and its treatment.

The different cell subsets of the immune system express vitamin D receptor (VDR). Through VDR, vitamin D exerts different functions which influences on immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies have explored the impact of vitamin D levels on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results have been confirmed in a prospective cohorts trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies has also been explored. Considering this dual effect both on the immune system as well as on tumor cells in patients with hematologic malignancies, vitamin D might be useful in this setting both to decrease graft-versus-host disease and relapse rates.

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study; real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)₂D₃. Frist; a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)₂D₃ treatment; suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation; gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1; SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1; no changes in gene expression were observed. However; a concomitant decrease in CAT and SOD1 mRNA; and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)₂D₃ treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

Background Candida auris is an emerging multidrug-resistant fungal pathogen that represents a serious threat to healthcare settings currently. Objective: Its objective was to determine the prevalence of C. auris in the hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts. and medical files of all suspected? and confirmed cases of C. auris cases reported at King Khalid University Hospital, Riyadh between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infection in our facility. We established our initial prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed cases positive for C. auris during the study period, 33 (62%) were males. Their ages ranged between 15 and 98; most positive cases occurred in 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and Urine samples yielded the greatest number of positive cases while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence could serve as our baseline/benchmark to compare with regional and international benchmarks.

The theory of heterogeneous nucleation was initially developed as a part of condensed matter physics and later it was used as an important engineering tool to design metallurgical processes. The success leads to wide applications of the theory in metallurgical practice. For example, engineering heterogeneous nucleation in ductile iron has been used to reduce shrinkage defects, suppress cementite formation, and modify size and shape of micro-structural constituencies. This demonstrates how theoretical knowledge could benefit industry practice. This overview aims to summarize the authors’ published studies in co-authorship with colleagues and students, which covered different aspects of engineering heterogeneous nucleation in multiphase cast alloys. Several approaches for engineering heterogeneous nucleation using thermodynamic simulation and practical methods for improving efficiency of nucleation using co-precipitation technique and a local transient melt supersaturation were suggested. Automated Scanning Electron Microscopy Energy-Dispersive-X-ray (SEM/EDX) analysis and a high-resolution Transmission Electron Microscopy (TEM) were used to verify simulation predictions. Practical examples of controlling micro-porosity shrinkage in cast irons with spheroidal graphite are presented to illustrate the power of engineering heterogenous nucleation. The authors appreciate the great efforts that the co-authors have made on the original, overviewed articles here.

On April 17, 2019, a coach with tourists from Germany crashed in Madeira requiring repatriation by the German Air Force. The Advance Trauma Life Support (ATLS) concept was the central component of patient care. Data in Madeira were collected through a structured interview. The analysis of the Aeromedical Evacuation was based on intensive care transport records. In Germany all available were reviewed for data collection. Quality of life (HRQoL) was evaluated by the 12-item Short-Form Health Survey (SF-12). Twenty-eight prehospital patients were transported to the Level III Trauma Center in Funchal (Madeira). Five operative procedures were performed. Fifteen patients were eligible for Aeromedical Evacuation (AE). In the second hospital phase in Germany in total 82 radiological images and nine operations were performed. Hospital stay lasted 11 days (median, IQR 10–18). Median Follow-up (14 of 15 patients) was 16 months (IQR 16–21). 80% (8 out of 10) showed an increased risk for post-traumatic stress disorder (PTSD). Six key findings were identified in this study: divergent injury classification, impact of AE mission on health status, lack of communication, need of PTSD prophylaxis, patient identification, media coverage. Those findings may improve AE missions in the future e.g. required after armed conflicts.

Synthetic bone made of calcium phosphate is widely used for the clinical treatment of bone defects caused by trauma and bone tumors. Although synthetic bone is easy to use, its effects are only partial depending on the size and location of the bone defect, and there are many treatment options other than the use of synthetic bone. Various biodegradable polymers that are being considered for use as scaffolds for regenerative medicine are also being considered for use as synthetic bones; however, commercial synthetic bone products with performance comparable to that of calcium phosphate bioceramics have not yet been clinically applied. This review introduces the practice of bone regeneration therapy with synthetic bone and recent research on bone regeneration therapy with biodegradable polymers.

Calcium sulfate (CS) materials containing terbium ions at 0, 1.0, or 2.0 mol.% were obtained by mechanochemical synthesis. According to X-ray diffraction data, the powder materials are characterized by the presence of a CaSO4×0.5H2O phase, while Tb3+ is incorporated into the lattice at ≤1.0 mol.%. Specific surface area enlarged from 2.1 to 22.5 m2/g as crystallite size decreased from 68 to 31 nm and the Tb3+ concentration increased up to 1.0 mol.%. Thermal analysis showed that terbium slightly raises the temperature of CaSO4×2H2O-to-CaSO4 transition. The presence of Tb3+ did not affect the solubility of the CS cements. Furthermore, after 7 days of soaking of the materials in a simulated body fluid, a calcium phosphate layer formed corresponding to a hydroxyapatite phase, in contrast to the pure cements. Luminescent properties were studied by excitation at 276 nm. The recorded emission peaks of the CS materials indicated that the luminescence of the samples is green and blue, with the most intense luminescence observed for samples containing 1.0 mol.% Tb3+. The developed materials can find applications in medicine as bioimplants for the regeneration and restoration of bone tissue with a possibility of noninvasive monitoring of the bone restoration process.

Water is essential for all living things however its pain has become serious. Many industrial activities cause its pollution by the release of polluting byproduct. Waste water treatment is hence necessary. In this context, the waste water of the textile industry containing Red Acid 52 was treated by the solid waste of the washed natural phosphate byproduct. Natural phosphate was also studied. The solid materials were first characterized by chemical analysis, Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The phosphate materials were after that, tested in the adsorption of the Red Acid 52. The experimental data indicated that the phosphate waste rock allowed the removal of Red Acid 52. Its maximum retention capacity attained 18.4 mg.g-1. Calcinations of materials inhibits the removal capacity found reduced by 60 to 70%. The adsorption kinetics of the Red Acid 52 on the material is well described by the pseudo second order model while the adsorption isotherms are identified by the Langmuir model. Hereafter, the thermodynamic study revealed that the adsorption process is spontaneous and exothermic. Keywords: Waste water, Phosphate co-product, Adsorption, Red Acid 52.

Adenine nucleotide (AN) 2^nd messengers such as 3’,5’-cyclic adenosine monophosphate (cAMP) are central elements of intracellular signaling, but many details of underlying processes remain still elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca²⁺ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Consequently, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.

The aim of the study was to determine the maximum safe concentration of calcium and phosphate in neonatal parenteral nutrition (PN) solutions when various combinations of inorganic and organic salts are applied. Twelve PN solutions for neonatal use were aseptically prepared. Increasing concentration of inorganic and organic calcium and phosphate were added to the standard formulas. Each admixture was separately tested according to following conditions; after mixing, 37°C for 24 h, and maximum safe combination of calcium and phosphate were stored at 4°C for 30 days and followed by 24 h at 37°C. Visual inspections against a black and white contrast background, microscopic observation of undiluted PN solutions as well as the membrane filter after filtration of the PN solution, pH evaluation, and spectrophotometry at 600 nm were examined in triplicate. Safe maximum concentration of organic and inorganic calcium and phosphate was proposed individually for each composition of parenteral nutrition solutions. Surprisingly organic calcium with organic phosphate showed precipitation but over the therapeutic range. The protective effect of amino acid was observed and higher concentrations of calcium and phosphate were free of precipitation.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

As mental health problems tend to increase during adolescence and is a serious public health issue in the Republic of Kazakhstan. Early detection is necessary and monitoring at the population level can be used to evaluate the progress of national programmes promoting positive well-being. Physical activity (PA) can be protective whereas increased screen time behaviours (STB) can be a risk for low levels of well-being. A national representative sample (n=4,731) of young adolescents aged 11y, 13y, and 15y from the Republic of Kazakhstan took part in the WHO collaborative Health Behaviour in School-aged Children (HBSC) study. Respondents completed the WHO-5 Well-being scale, and items in on PA and STB. Internationally recognised, recommended cut-offs were used for analyses. Two models of binary logistic regressions were performed to examine the associations with PA (Model 1) and PA with STB (Model 2) after stratification by gender and controlling for age, locality and family affluence. Three quarters of young adolescents in the Republic of Kazakhstan have good overall well-being, despite the proportion reduces as adolescents age from 11y to 15y (boys, OR=0.66 CI=0.49-0.80; girls, OR=0.55, CI=0.43-0.71). The odds ratio for positive well-being were more than twice for boys and more than 3.5 for girls who reported daily PA than not being active daily. Spending less time on STB for girls was associated with positive well-being than spending more STB time (OR=1.28, CI=1.04-1.59). Well-being among young adolescents drops dramatically between the ages of 11y and 15y and is higher among rural schools attendees than in urban schools. The recommended amounts of PA can be protective of low well-being for both boys and girls. However, meeting reporting STB recommendations was only protective for girls and not boys. Designing and implementing positive well-being programmes require consideration of locality and amounts of PA and STB

The string of bacteria, Vibrio. sp. QD-5 utilizing alginate, was separated from rotten kelp. The results of genome sequencing showed that the strain QD-5 contained four alginate lyase genes.One of the alginate genes Aly-IV was cloned and linked to the plasmid pET-22b (+). The heterologous expressed alginate lyase aly-IVwas characterized，which possessed the theoretical molecular mass of 62 kDa, and theoretical isoelectric point (pI) of 5.12. - The enzyme aly-IV was purified and the activity reached 1256.78 U/mg, with optimal temperature of 35 ^oC and pH value of 8.9. Nurtured in the temperature below 25 ^oC for 30 minutes, the activity was almost stable. The result also suggested that the activity of enzyme was strongly affected by - NaCl whose optimal concentration was 15 mM in a lab environment The TLC and ESI-TOF-MS analysis suggested that the enzyme aly-IV could degrade sodium alginate and polyG in endo-lytic type, producing monomer, dimer and trimmer. So, aly-IV can also be widely applied to make large scale preparation of alginate oligosaccharides with low degree of polymerization (DP).

Sodium-phosphate-based glass-ceramics (GCs) are promising materials for a wide range of applications, including solid-state sodium-ion batteries, microelectronic packaging substrates, and humidity sensors. This study investigates the impact of 24-hour heat-treatments at varying temperatures on Na-Ge-P glass, with a focus on (micro)structural, electrical, and dielectric properties of prepared GCs. Various techniques such as powder X-ray diffraction (PXRD), infrared spectroscopy-attenuated total reflection (IR-ATR), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) are employed. With the elevation of heat-treatment temperature, crystallinity progressively rises; at 450 °C, the microstructure retains amorphous traits featuring nanometric grains, whereas at 550 °C, heat-treatment results in fully crystallized structures characterized by square-shaped micron-scale grains of NaPO3. The insight into the evaluation of electrical and dielectric properties is provided by Solid-State Impedance Spectroscopy (SS-IS), revealing a strong correlation with the conditions of controlled crystallization and observed (micro)structure. The glass-ceramic heat-treated at 450 °C achieves the highest DC conductivity of 2.30×10–8 Ω–1 cm–1 at 393 K. As the heat-treatment temperature rises, the crystallization of the NaPO3 phase depletes the glass matrix of mobile Na+ ions, resulting in a reduction in DC conductivity. Dielectric parameters also decrease with rising heat-treatment temperature, with the glass-ceramic heat-treated at 550 °C displaying the lowest permittivity of 19.37 and the dielectric loss of 0.008. This research uncovers the intricate relationship between heat-treatment conditions and material properties, emphasizing that controlled crystallization allows for precise modifications to microstructure and phase composition within remaining glassy phase, ultimately facilitating fine-tuning of material properties.

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

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

Background and Objectives: Previous studies revealed anti-angiogenic, antiproliferative and anti-inflammatory effects of Vitamin D on cancer cells. Although this body of evidence supported the correlation of high Vitamin D levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). Aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on Vitamin D serum status, dietary intake, and Vitamin D receptor (VDR) polymorphisms in correlation to NMSC incidence. Materials and Methods: A literature search in electronic databases was conducted from inception to January 2023. Inclusion criteria were systematic reviews and meta-analyses published in peer-reviewed journals, evaluating Vitamin D serum levels, dietary and/or supplementary intake, or VDR gene polymorphisms, and reporting data on NMSC. Results: A total of 10 studies were included in the data analysis models. A positive association between Vitamin D serum levels and NMSC is highlighted. However, dietary/supplementation of Vitamin D doesn’t exhibit a likewise strong linkage to NMSC. Despite the contradictory findings, VDR polymorphisms may play a crucial role in the intricate NMSC pathogenesis. Conclusions: This umbrella review showed that high Vitamin D levels are associated with increased NMSC incidence, potentially due to its direct correlation with increased sun exposure. Further research on VDR polymorphisms is suggested to explore their true effect size on NMSC risk.

Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

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

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

Diagnosis of kidney diseases has recently become more comprehensive and accurate by using new renal markers. Despite the fact that creatinine and cystatin c have been sufficient in determining kidney function, they did not indicate the exact site of the damage and they were often insufficient in predicting the course of the disease. Aim of the study was to evaluate the potential correlations and differences in levels of six factors related to kidney function and injury: kidney injury molecule-1 (KIM-1), ncalbindin (CALB), glutathione S-transferase Pi (GST-Pi), calbindin and monocyte chemoattractant protein-1 (MCP-1), between renal patients with diabetic nephropathy (DM), congenital defects (CD) of the kidney and glomerulonephritis (GN). Study involved 75 patients: 49 with diabetic nephropathy, 12 with congenital defects and 14 with glomerulonephritis. Levels of renalase was measured using immunoenzymatic tests. Levels of other markers: calbindin, glutathione-S-transferase (GST-pi), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were analyzed using Kidney Toxicity-1 Panel and BioPlex system, designed for analyses in urine and optimized by us for serum.From all analyzed markers, only levels of KIM-1 differed significantly between any subgroups, and that was for CD and DM. Renalase correlated significantly negatively with creatinine and positively with all other markers, apart from MCP-1. Obtained results indicate, that serum renalase, KIM-1, calbindin and GST-pi are related to kidney function, with KIM-1 being the most exact, while MCP-1 levels are unrelated to creatinine and glucose levels, does not differ between patients with diabetic nephropathy and other subgroups, and therefore seem to be independent of diabetes. Also, serum-optimized Kidney Toxicity Panel 1 kit for determination of selected markers gave results similar to previous ones and therefore the method can be valuable in determination of analyzed factors.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

Footprints are powerful indicators for evaluating the impact of the bioeconomy of a country on environmental goods, domestically and abroad. In this study, we apply a hybrid approach combining a Multi-Regional Input-Output model and land use modelling to compute the agricultural land footprint (aLF). Furthermore, we added information on land-use change to the analysis and allocated land conversion to specific commodities. The German case study shows that the aLF abroad is larger by a factor of 2.5 to 3 than the aLF in Germany. In 2005 and 2010, conversion of natural and semi-natural land-cover types abroad allocated to Germany due to import increases was 2.5 times higher than the global average. Import increases to Germany slowed down in 2015 and 2020, reducing land conversion attributed to the German bioeconomy to the global average. The case study shows that the applied land footprint provides clear and meaningful information for policymakers and other stakeholders. The presented methodological approach can be applied to other countries and regions covered in the underlying database EXIOBASE. It can be adapted, also for an assessment of other ecosystem functions, such as water or soil fertility.

Mexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). PAX8 defects underlie only 1% of these cases and NKX2-1 does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patients (females 77.3%; 6 months to 16.6 years) with non-syndromic CH-TD diagnosis established by clinical evaluation, thyroid hormone serum profiling, and scintigraphy (74%) or ultrasonography (26%). We performed Sanger sequencing of FOXE1, NKX2-5, and TSHR and evaluated copy number variations (CNVs) in TSHR, FOXE1, PAX8, and NKX2-1 by multiplex ligation-dependent probe amplification. Odds ratios for TD risk were explored for FOXE1 polyalanine stretches [polyAla-rs71369530] in cases and controls (N=116). Five rare missense changes cataloged as benign (NKX2-5:p.(Ala119Ser)-rs137852684), of unknown significance (FOXE1:p.(Ala335Gly)-rs543372757; TSHR:p.(Asp118Asn)-rs1414102266), and likely pathogenic (FOXE1:p.(Gly124Arg)-rs774035532; TSHR:p.(Trp422Arg)-rs746029360) accounted for 1.5% (N=2/128) of clinically relevant genotypes (supported in part by protein modeling) in CH-TD. No CNVs were identified, nor did polyAla &gt;14 alanines in FOXE1 significantly protect against TD. The present and previously published data collectively show that small clinically relevant germline variants in PAX8, FOXE1, and TSHR are found in only a very small proportion (2.5%) of isolated CH-TD Mexican patients.

A recent systematic review for 19 selected articles after searching through to 30 September 2017 showed vitamin D deficiency was associated with ischemic stroke (IS), not hemorrhagic stroke (HS). But a heterogeneity would be introduced with comparing the lowest and highest category of vitamin D. The aim of this article was to conduct an updated meta-analysis (UMA) with searching through to 31 March 2019. An interval collapsing method as information extraction was applied in order to decrease a heterogeneity among studies. Additional articles were selected from cited lists from 19 selected articles using citation discovery tools. Random effect model was applied if I-squared value was over 50%. A funnel plot and Egger’s test were used to detect a publication bias. After 5 new studies were added, the summary RRs [and their 95% confidence intervals] (I-squared value) were 1.52 [1.33–1.74] (0.0%) in IS, and 2.44 [1.34–4.46] (69.7%) in HS. This UMA supported the hypothesis that serum vitamin D deficiency was associated with an increased risk of HS as well as IS. Diverse public health programs against vitamin D deficiency status would be needed for higher risk group, especially elderly people.

Upland cotton is sensitive to 2,4-dichlorophenoxyacetic acid (2,4-D), and the identification of potentially 2,4-D tolerant cotton chromosome substitution (CS) lines and understanding tolerance mechanisms provide a significant step into the development and genetic improvement of upland cotton to reduce yield loss caused by 2,4-D herbicide effects including the drifts. Experiments were conducted to understand the possible mechanism of herbicide tolerance in CS-T04-15, CS-T07, and CS-B15sh, 2,4-D herbicide-tolerant cotton CS lines compared with TM-1, the 2,4-D herbicide susceptible recurrent parent of the CS line as control, using [14C]2,4-D. Percent absorption rate and translocation patterns of the 14C-labeled herbicide application at 5.17 kBq at 6 to 48 hours after treatment (HAT) were determined. The tolerant cotton CS lines showed 15-19% [14C]2,4-D uptake while TM-1 exhibited a reduced uptake of only 1.4% [14C]2,4-D at 24 HAT. Distribution of the absorbed [14C]2,4-D showed that 2-5% was translocated outside the treated leaf. In TM-1, 77% of the herbicide was translocated above and below the treated leaf, contrasting with the reduced translocation of 14C-labeled herbicide observed in the tolerant CS lines. Interestingly, CS-T04-15 showed a restricted movement of 14C below the treated leaf at 6 to 48 HAT, suggesting a novel mechanism of herbicide tolerance. This finding is the first report on upland cotton demonstrating a complex differential uptake and translocation associated with herbicide tolerance for [14C]2,4-D in cotton CS lines.

Backgroundː Previous studies have shown that both serum creatinine and D-dimer levels were associated with atherosclerotic coronary artery disease (CAD). We aimed to determine whether DCR is associated with coronary Gensini score in patients with ST-elevation myocardial infarction (STEMI). Methodsː 337 STEMI patients with complete D-dimer and creatinine and other necessary information were included in the analysis. According to the values of the DCR, patients were divided into the lower DCR group (DCR ≤ 1.42, n = 173) and the higher DCR group (DFR > 1.42, n = 174), and the differences between the two groups were compared. Multivariate linear and multivariate logistic regression analyses were performed to determine independent predictors of Gensini score. Resultsː High DCR group had higher Gensini score compared with low DCR group (P < 0.05). DCR was positively correlated with Gensini score (r=0.493, P < 0.001). Multiple linear regression analysis showed that Previous MI (r=11.312, P=0.035) and DCR (r=5.129, P<0.001) were independent risk factors associated with Gensini score. Multivariate logistic regression analysis showed that, compared to the group 1, DCR is independent risk factor for Group 2, Group 3, Group 4 (P <0.001). DCR is positively correlated with coronary Gensini score in STEMI patients and can be used as an independent predictor of higher Gensini score. Conclusionsː As a new and useful clinical marker, DCR is positively correlated with coronary Gensini score in STEMI patients and can be used as an independent predictor of higher Gensini score.

Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them, and moreover, their combinations have been studied wide enough in terms of their in-fluence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′ end lipophilic (single cholesteryl or pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combi-nation of used lipophilic groups with phosphate modifications of various nature and different position on the efficiency of cell penetration was evaluated. Obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the ra-tional design of oligonucleotide structures with desired predefined properties.

Enamel erosion is a process which happens every time we eat and it may be accelerated by some particular acid foods, drinks or other agents. Dental enamel when damaged by low pH substances becomes chalky, rough, opaque, yellowed and it can be related to dentinal hypersensitivity. To the present day, several possible solutions are available, therefore the aim of this study was to evaluate the effect of a biocompatible minerals serum based on calcium silicate, sodium phosphate and fluoride (Regenerate™) on the damaged enamel by four different acid liquids. 135 ovine teeth were equally divided into 5 groups and submerged for one week into lemon juice, energy drink, coffee, tea and physiologic solution for the negative control. The first 4 groups were evaluated for their color with an analogical color scale (Vita® Scale) and for their surface assigning a qualitative aspect among opaque, rough, chalky or smooth. Then they were treated with hydroxyapatite gels and re-evaluated for the same parameters. Data were checked for the normal distribution with Shapiro-Wilk test and analyzed with dependent t-test or Wilcoxon Signed Rank test, every test with a p≤0.05. Both color and surface aspect showed a strongly significant improvement after the treatment. Biocompatible minerals serum based on hydroxyapatite is able to reverse teeth erosion, improve the color and restore the smoothness of the dental enamel.

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.

The sepiolite/ZrO2 composites were prepared by sepiolite (Sep) modification with zirconium propoxide in toluene, at room temperature for 24 h (Sep –ZrI) or 95 °C for 4h (sample Sep –ZrII). The efficiency of the obtained adsorbents for the removal of phosphate from aqueous solutions at initial pH = 4 and pH = 8, was investigated. Characterization of the samples showed that higher temperature of synthesis for shorter time provided slightly higher content of amorphous Zr-phase, which was deposited on sepiolite fibers as a thin layer and agglomerated nanoparticles. Compared to Sep, the composites had lower point of zero charge and higher specific surface area and pore volume. The adsorption kinetics follows the pseudo second-order model. The adsorption capacities of the composites were approximately the same at both initial pH and higher at initial pH = 4 than at pH = 8. The XPS and ATR-FTIR of Sep-ZrI before and after adsorption identified the formation of inner-sphere complexes as the mechanism of phosphate adsorption. The slow release during desorption with NaOH solution confirmed strong bonds of phosphates with the surface of the composites.

The anodic polarization response of magnesium alloy AZ31 was characterized during exposure to aerated 0.1M NaCl solutions with millimolar additions of NaVO₃, Na₃PO₄, Na₂HPO₄, NaF and various pairings to assess their ability to inhibit corrosion kinetics and retard localized corrosion. Each of the candidate inhibitors reduced the corrosion rate of the alloy to some degree. A Na₃PO₄ - NaVO₃ pair produced a powerful inhibiting response decreasing the corrosion rate to about 10^-7 A/cm², which was two orders of magnitude lower than the uninhibited control case. A Bliss Independence assessment indicated that this inhibitor pair acted synergistically. A Na₂HPO₄ - NaVO₃ pair reduced the corrosion rate to 10^-6 A/cm² but was not assessed to be acting synergistically. The NaVO₃ - NaF pair did not reduce the corrosion rate significantly compared to the control case and was an antagonistic pairing. SEM imaging showed film formation due to exposure, which appears to be the origins of the observed inhibition. The resistance to localized corrosion was assessed as the difference in the breakdown potential and the corrosion potential with larger values indicating a lower probability of localized corrosion during free corrosion exposures. Effects of the inhibitors on this characteristic were mixed, but each of the inhibitor pairs yielded potential differences in excess of 100mV. A conceptual conversion coating process based on a mixture of vanadate and phosphate compounds were demonstrated. A fluoride-bearing formulation produced coatings whose total impedance was increased by a factor or 2 compared to an uncoated control. A fluoride-free formulation produced coatings whose corrosion resistance was increased by more than a factor of 3.

To achieve efficient and durable consolidation of weathered sandstone, the selection of a suitable consolidant is essential. To reasonably assess the suitability of different formulations, it is fundamental to compare their performance as a consolidant within a substrate, which reliably models the properties of deteriorated material. As a test substrate, the sandstone from quarries in Mšené in central Bohemia was selected, for its developed porosity and relatively low mechanical strength. To obtain relevant comparison of their application potential, both commercial (Remmers KSE OH and Surfapore) and self-developed consolidants were included. To test the long-term stability of each consolidant, the stone was subjected to accelerated weathering. The characterization of texture properties was based on the physical sorption of nitrogen and krypton, mercury intrusion porosimetry and water uptake. While the mechanical properties in microscale were determined by nanoindentation, the mechanical strength in macroscale before and after consolidation was measured by drilling resistance. Both commercial exhibited good mechanical performance with reasonable durability. The performance of our developed samples was comparable or, in some cases, superior. Very interesting were the consolidants containing TiO2 and ZnO nanoparticles, the former exhibiting comparable degree of consolidation and durability as commercial ones, with additional photocatalytic function, the latter unusually high increase in the mechanical strength, even after the weathering test. The diammonium hydrogen phosphate based consolidant showed exceptional durability in the weathering test, which makes it a promising product not only for carbonate but also sandstone materials.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. In addition, tadalafil protected cerebral nerve development in FGR offspring. The clinical trials we have conducted to date, including a case–control study, a phase I trial, and a phase II trial, have indicated the efficacy of tadalafil in prolonging pregnancy, as well as a good safety profile for fetuses and neonates. The number of fetal, neonatal, and infant deaths was significantly lower in those receiving tadalafil treatment group than that in controls, and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

As one of toxic Volatile Organic Pollutant (TVOCs), formaldehyde has a toxic effect on microorganisms, and then inhibits the biochemical process of formaldehyde wastewater treatment. Therefore, the selective degradation of formaldehyde is of great significance to achieve formaldehyde wastewater high-efficiency and low-cost treatment. This study constructed a heterogeneous Fe-ZSM-5/H2O2 Fenton system for selective degradation to target compounds. By bonding Fe3+ onto the surface of ZSM-5 molecular sieve, Fe-ZSM-5 was prepared successfully. XRD, BET and FT-IR spectral studies shown the prepared Fe-ZSM-5 was mainly composed of micropores. The influences of different variables on formaldehyde selective heterogeneous Fenton degradation performance were studied. The 93.72% formaldehyde degradation and the 98.15% selectivity of formaldehyde compared with glucose had demonstrated in the optimized Fenton system after 360 min. Notably, the resultant selective Fenton oxidation system had a wide range of pH suitability from 3.0 to 10.0. Also, the Fe-ZSM-5 was used in 5 consecutive cycles, while the degradation efficiency of formaldehyde did not drop dramatically. Using reactive oxygen species scavengers, hydroxyl radical was the main active substance to degrade formaldehyde. Furthermore, the great degradation performance of this system to high concentration of formaldehyde was acquired, and the degrading efficiency was more than 95%.

Rice blast fungus (Magnaporthe oryzae) causes massive yield losses annually worldwide. The fungus secreted bunch of effector proteins target different rice cellular compartments to facilitate its infection. However, most of intensively studied effectors are small secreted proteins with high presence/absence polymorphism in the fungus, and effectors conserved among different species were rarely investigated. In this study, we identified MoPce1, a CAP/PR domain containing protein common in different species, as an important virulence factor from a screening of 145 putative core effectors (PCE). MoPCE1 is required for pathogenicity but not the asexual development. Ectopic expression of MoPCE1sp in ZH11 background compromised the plant resistance. We also found that MoPce1 lacks the conserved cysteine residuals in CAP domain, and is BIC-localized in invasive hyphae and nuclei-localized when ectopically expressed in tobacco leaves and rice protoplasts. These results suggested that MoPce1 may bind novel ligand(s) rather than sterol. Indeed, we found that MoPce1 could interact with OsDi19-5, a transcription factor in rice. We inferred from these results that MoPce1 is required for pathogenicity by suppressing the immune response in rice, likely through the interaction with OsDi19-5.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

Autophagy, an alternative cell death mechanism, is also termed programmed cell death type II. Autophagy in cancer treatment needs to be regulated. In our study, autophagy inhibition by desipramine or the autophagy inhibitor chloroquine (CQ) enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 [death receptor (DR5)] expression and subsequently TRAIL-induced apoptosis in TRAIL-resistant A549 lung cancer cells. Genetic inhibition of DR5 substantially reduced desipramine-enhanced TRAIL-mediated apoptosis, proving that DR5 was required to increase TRAIL sensitivity in TRAIL-resistant cancer cells. Desipramine treatment upregulated p62 expression and promoted conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, indicating that autophagy inhibition occurred at the final stages of autophagic flux. Transmission electron microscopy analysis showed the presence of condensed autophagosomes, which resulted from the late stages of autophagy inhibition by desipramine. TRAIL, in combination with desipramine or CQ, augmented the expression of apoptosis-related proteins cleaved caspase-8 and cleaved caspase-3. Our results contributed to the understanding of the mechanism underlying the synergistic anti-cancer effect of desipramine and TRAIL and presented a novel mechanism of DR5 upregulation. These findings demonstrated that autophagic flux inhibition by desipramine potentiated TRAIL-induced apoptosis, suggesting that appropriate regulation of autophagy is required for sensitizing TRAIL-resistant cancer cells to TRAIL-mediated apoptosis.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

The field of mitochondrial genomics has advanced rapidly and revolutionized disciplines from molecular anthropology, population genetics, to medical/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated, mitogenome database and efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4,286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient and accurate means of sequence analysis for translational mitogenomics.

Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

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

Rapid industrialization, urbanization, and population explosion in sub-Saharan Africa escalate environmental Lead levels with subsequent elevation of blood Lead levels in children. Nutrition status, age, and genetics govern one’s susceptibility to Lead toxicity. This study expounded this susceptibility by relating blood Lead levels, d-aminolevulinic acid dehydratase enzyme activity (ALAD), and genetic variations of proteins that code for ALAD enzyme in urban children of Uganda. Spectrophotometric analysis for blood Lead (BL), hemoglobin levels, and determination d-levels aminolevulinic acid dehydratase enzyme activity of the blood samples from 198 children were performed prior to a polymerase chain reaction and restriction fragment length digestion for ALAD polymorphism was done. Up to 99.5% of samples coded for the ALAD1 allele whereas 0.05% coded for ALAD2. Genotypes ALAD2-2 members had elevated BLL (mean 14.1 µg/dL) and reduced ALAD enzyme activity compared to others. This, therefore, implies that the majority of children hoard BL which may affect them later in life.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (&gt;200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p&lt;.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

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

In this paper, we present the interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles and cytisine and salsoline alkaloids. It has been shown that the reaction results in the one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction is affected by the presence of a base and the order in which the reagents are added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity has been carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking shows that the compounds have insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increases the affinity of these substrates for target proteins selected.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

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.

Abstract. Graphene family (GF)-Calcium phosphate (CaP) composites, holds great potential as components of bone regeneration materials. GF nanomaterials can be modified physically as well as chemically, which are to be biomimetic, mechanically to be hard due to their capability to support exceptional mechanical, thermal and electronic properties. These biocompatible GF composites coated on the calcium phosphate can enhance and tolerate stem cell growth and differentiation, proliferation into various lineages or interact with bioorganisms. The development in CF-CaP materials and their physicochemical/biointeractions and strategies towards osteoblasts is a great concern to promote faster healing and reconstructions of large bone imperfections or defects. In this review, we explain the influence of the CF-CaP and summarize recent developments on designing CF-CaP architectures as multifunctional bone regeneration platforms. We have also explored the typical biological applications concerning these CF-CaP based bioactive nanocomposites. Furthermore, the future viewpoints and evolving challenges will also be emphasized. Due to the shortage of full-length reviews in this emerging research field, this review would be caught great attention and encourage various new chances across a wider range of disciplines.

Phosphate (Pi) starvation is a critical factor limiting crop growth, development, and productivity. Rice (Oryza sativa) R2R3-MYB transcription factors function in the transcriptional regulation of plant responses to various abiotic stresses and micronutrient deprivation, but little is known about their roles in Pi starvation signaling and Pi homeostasis. Here we identified the R2R3-MYB transcription factor gene OsMYB58, which shares high sequence similarity with AtMYB58. OsMYB58 expression was induced more strongly by Pi starvation than by other micronutrient deficiencies. Overexpressing OsMYB58 in Arabidopsis thaliana and rice inhibited plant growth and development under Pi-deficiency conditions. In addition, overexpression of OsMYB58 in plants exposed to Pi deficiency strongly affected root development, including seminal root, lateral root, and root hair formation. Overexpressing OsMYB58 strongly decreased the expression of the rice microRNAs, OsmiR399a and OsmiR399j. By contrast, overexpressing OsMYB58 strongly increased the expression of rice PHOSPHATE 2 (OsPHO2), whose expression is repressed by miR399 during Pi starvation signaling. OsMYB58 functions as a transcriptional repressor of the expression of its target genes, as determined by a transcriptional activity assay. These results demonstrate that OsMYB58 negatively regulates OsmiR399-dependent Pi starvation signaling by enhancing OsmiR399s expression.

This research was specifically aimed at assessing the influence of sulfur in triple-super phosphate (TSP) on wheat yield. From the results, wheat showed response to sulfur (S) from gypsum (in 67%); and nitrogen (N) from urea in about 100% (of 24 sites). Based on this N was found to be the most limiting element to wheat production followed by sulfur, and then by phosphorus. TSP is tested to contain agronomically up to 2-6% by weight of S. However, wheat didn’t show response to S impurity supplied in the form of TSP. Though, not statistically significant, it is observed that there have always been yield increments by certain percent due to S from TSP in 8 out of 10 target sites, which is depicted in the increasing trends of yield response curves. From this it is learnt that, the benefits of the accidental/incidental application of such high analysis fertilizers can be many-folds in the quality attributes of wheat, if the soils of such investigation at the same time would contain significant amount of organic matter (OM). Indeed, such analysis would be vital in varietal specific nutrient requirement studies in precision-farming and/or in categorizing soils into fertility gradients and fertilizer recommendation domains.

Astronauts at are risk of losing 1.0 – 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs designed to preserve the musculoskeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth facor-1 and its receptor IGFR1 play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, and sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

(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.

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Viruses pose a great threat to people’s lives. Enterovirus A71 (EV-A71) infects children and infants all over the world with no FDA-approved treatment to date. Understanding the basic mechanisms of viral processes aids in selecting more efficient drug targets and designing more effective antivirals to thwart this virus. The 5´-untranslated region (5’-UTR) of the viral RNA genome is composed of a cloverleaf structure and an internal ribosome entry site (IRES). Cellular proteins that bind to the cloverleaf structure regulate viral replication, while those that bind to the IRES also known as IRES trans-acting factors (ITAFs) regulate viral translation. In this review, we survey the cellular proteins currently known to bind the 5’-UTR and influence viral translation and replication with emphasis on comparing proteins’ functions and localizations pre- and post-(EV-A71) infection. Comprehensive understanding of how the host cell’s machinery is hijacked and reprogrammed by the virus to facilitate its replication is crucial for developing effective antivirals.

The search for a continuous continental record of interglacial periods in semi-arid regions is problematic due to the absence of stable and continuous sedimentary systems over time in this type of climate. In this work, a relatively stable basin is described and analyzed during the last interglacial in a semi-arid region of the western Mediterranean. For this purpose a geomorphological, stratigraphic and sedimentological study has been carried out, with dating through 230Th. A semi-endorrheic Pleistocene basin has been identified, with two units that correspond to a fluvial-lacustrine system (unit P1) and an alluvial system (unit P2). Unit P1 has been dated in the MIS 5e interglacial episode. A framework is described in which the Aljezares Quaternary basin can be considered as a possible source of paleoenvironmental and paleoclimatic information in semi-arid regions from the last interglacial period in future studies.

Reduced glutathione (GSH) is an antioxidant in plants and is one of the important ways for plants to combat low-temperature stress. In this paper, Eriobotrya japonica Lindl. cv. Zaozhong No. 6 seedlings were used to study the effects of exogenous 5-aminolevulinic acid (ALA) application on glutathione synthesis and cyclic metabolism of loquat seedlings under low-temperature stress and to explore the regulatory mechanism of ALA on loquat cold tolerance. The results showed that ALA treatment could increase the content of GSH and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in loquat leaf slices under low-temperature stress; reduce the electrolyte leakage rate and GSSG, H₂O₂ and MDA contents in leaf tissues; and alleviate the peroxidation damage caused by low temperature. ALA treatment increased the activity of γ-glutamine synthetase (γ-ECS) in loquat leaf slices under low-temperature stress and promoted the biosynthesis of reduced glutathione, thereby increasing the GSH content in leaf tissues. On the other hand, ALA treatment could also improve the activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and promote the cyclic regeneration of GSH, accordingly maintaining a high GSH/GSSG ratio, promoting the removal of reactive oxygen species (ROS), and enhancing the antioxidant capacity of leaves. The regulatory effect of ALA on enhancing the antioxidant capacity of loquat seedlings under low-temperature stress can be inhibited by L-buthionine-sulfoximine (BSO, GSH biosynthesis inhibitor). The results showed that ALA improved the antioxidant capacity of loquat seedlings under low-temperature stress, and GSH was involved in the regulation of the antioxidant effect of ALA on loquat seedlings under low-temperature stress.

Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to develop further more potent TAAR5 ligands with putative anxiolytic and antidepressant activity.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the road for the emerging nanomedicine as a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 was reported in lung, colon, metastatic breast cancers and bladder squamous carcinoma. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. Sildenafil had been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the expression of Bad and Bax proapoptotic proteins. It was also reported that the use of sildenafil prior to the administration of Doxorubicin (DOX) increased its EPR-related concentration in breast cancer tissues by 2 folds. Further, a substantial reason of anticancer chemotherapeutic failure is due to multidrug resistance (MDR), exacerbated by the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCCs. Sildenafil has demonstrated inhibitory effects on the efflux activity of ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing MDR caused by these transporters. In this review, we critically examine the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery pointing up the outcome of the most important related preclinical and clinical studies.

In this article we report the first investigation over time of the atmospheric conditions around TGFs occurrence, using GPS sensors in combination with geostationary satellite observations and ERA5 reanalyses data. The goal is to understand which characteristics are favourable to the development of these events and to investigate if any precursor signals can be expected. A total of 9 TGFs, occurred at a distance lower than 45 km from a GPS sensor, were analysed and two of them are shown here as an example analysis. Moreover, the lightning activity, collected by the World Wide Lightning Location Network (WWLLN) was used in order to identify any links and correlations with TGF occurrence and PWV trends. The combined use of GPS and the stroke rate trends identified, for all cases, a recurred pattern in which an increase of PWV is observed on a timescale of about two hours before the TGF occurrence that can be placed within the lightning peak. The temporal relation between the PWV trend and TGF occurrence is strictly related to the position of GPS sensors in relation to TGF coordinates. The life cycle of these storms observed by geostationary sensors, described TGFs producing clouds as intense with a wide range of extensions and, in all cases, the TGF is located at the edge of the convective cell. Furthermore, the satellite data give an added value in associating the GPS water vapor trend to the convective cell generating the TGF. The investigation with ERA5 reanalyses data showed that TGFs mainly occur in convective environment with not exceptional values with respect to the monthly average value of parameters measured in the same location. Moreover the analysis showed the strong potential of the use of GPS data for the troposphere characterization in areas with complex territorial morphology. This study provided indications on the dynamics of convective systems linked to TGFs and will certainly help refine our understanding on their production highlights a potential approach through the use of GPS data to explore the lightning activity trend and the TGFs occurrence.

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

The three heat-induced coffee contaminants acrylamide, furfuryl alcohol (FA) and 5-hydroxymethylfurfural (HMF) were analyzed in a collective of commercial samples as well as in Coffea arabica seeds roasted under controlled conditions from very light Scandinavian style to very dark Neapolitan style profiles. Regarding acrylamide, average contents in commercial samples were lower than in a previous study in 2002 (196 compared to 303 µg/kg). The roasting experiment confirmed the inverse relationship between roasting degree and acrylamide content, i.e. the lighter the coffee the higher the acrylamide content. However, FA and HMF were inversely related to acrylamide and found in higher contents in darker roasts. Therefore, mitigation measures must consider all contaminants and not be focused isolatedly on acrylamide, specifically since FA and HMF are contained in much higher contents with lower margins of exposure compared to acrylamide.

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

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

Use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated to exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally lower. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the tran-scriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP.

Management of calcium and phosphate in biofluids is key to maintaining physiological mineral homeostasis (i.e., appropriate mineralization of hard tissues and an absence of mineral deposition in soft tissues). This review describes and contrasts the ways vertebrates manage calcium phosphate in two biological fluids (breast milk and serum) and illustrates the benefits of mineral sequestration by proteins. In milk, phosphoprotein-sequestered calcium magnesium phosphates provide nutritional support, whereas in serum, protein-sequestered calcium phosphates control transport and delivery of calcium and phosphate to tissues for biological function or excretion. In addition, subsets of sequestered phosphates in serum have been identified as culprits underlying ectopic deposition of calcium phosphates and toxicity.

Applying of blood biopolymers to regulate the phase composition is promising in designing the hydroxyapatite-based hybrid biomaterials with controllable resorbability. Hybrid materials based on hydroxyapatite and platelet-poor plasma (PPP) were formed in conditions of chemical precipi-tation at pH 11, [Ca2+] / [PO43–] ratio 1.67, PPP volume fraction of 6–24%, maturing time of 4–9 days. Mineral component of the materials was represented as 53% hydroxyapatite / 47% amor-phous calcium phosphate after 4 days of maturation, and 100% hydroxyapatite after 9 days of maturation. Varying PPP content from 6% to 24% provided forming of materials with rather de-fined content of amorphous calcium phosphate and biopolymer component, having desired mor-phology ranging from typical apatitic conglomerates to hybrid apatite-biopolymer fibers. Co-precipitated hybrid materials based on hydroxyapatite and PPP are promising for bone regen-eration in osteoplastic and maxillofacial applications.

A notable REE mineralization in Europe is associated with the Ditrău Alkaline Massif (DAM) in the Eastern Carpathians (Romania). It is an expression of the latest hydrothermal phase in the DAM and is found in the form of mineralized carbonate veins cross-cutting the complex in the NW (Jolotca region) and the SE (Belcina region) parts of the DAM. In the Belcina veins monazite-(Ce), xenotime-(Y), apatite, together with Fe-Mg-rich carbonate, thorite, thorogummite, gedrite and plagioclase are rock-forming. Three different textural and chemical types of the monazite-(Ce) and the xenotime-(Y) document a three-stage evolution. The relative phosphate age succession (from older to younger) thereby is xnt1 > xnt2 (>)+ mnz1 + Fe2O3 + Fe-gedrite > mnz2 + Fe-dolomite (+ plagioclase) > mnz3 + xnt3 + apatite. Phosphate chemistry shows that these crystallized from hydrothermal fluids, whereby each phosphate type follows a separate evolutionary path recommending growth from (at least) 3 independent and successive hydrothermal fluids. Chemistry and pathways within the DAM suggest that these hydrothermal fluids could be derived from a subsurface carbonatitic intrusion. Mnz1,2 and xnt1,2 ages are tightly cluster at 215.8 ± 0.7 Ma (Norian, Upper Triassic). The third-generation phosphate ages are younger, but associated with large analytical uncertainties and did not deliver geologically useful ages. The mean age of ca. 216 Ma is interpreted as timing the Belcina REE mineralization, what together with the fluid chemistry, supports a model of the presence of a late-stage, independent carbonatitic intrusion about 10 Ma after the main igneous activity (ca. 235 - 225 Ma) forming the DAM, synchronous with extension-related magmatism in the region.

The flow behavior of the administrated fluid matrices demands careful assessments for stability as consumed by individuals with dysphagia. In the present study, we incorporate tapioca starch (TS), hydroxypropyl distarch phosphate (HDP), and xanthan gum (XG) as thickeners into different nectars (300±20 mPa.s) undergoing thermal processing and evaluated their stability. The thickened nectars presented better water holding and oil binding capacities at 25 ℃ than 4 ℃, and the nectars with TS provided the best results for both capacities as well as the highest solubility index and swelling power (p<0.05). All prepared nectars appeared to be shear-thinning fluids with yield stress closely fitting the power law and Casson models. XG-contained nectars presented a higher yield stress and consistency index. Matrices thickened by HDP exhibited a higher viscoelastic property compared to those thickened by TS during thermal processing. TS nectars presented viscous behavior, whereas HDP and XG nectars presented elastic behavior at 80 ℃ processing. The 3-min thermal processing HDP-nectars remained stable and met dysphagia-friendly requirements under 4 ℃ storage for 28 days regardless of the types of fluid bases (distilled water, sport drink, or orange juice). The employed thickeners present adequate physicochemical properties to be potentially utilized for producing dysphagia-friendly formulations.

Cadmium (Cd) is a heavy metal that suppresses plant growth; however, application of endophytic bacteria can increase resistance of plants against Cd, as well as improve plant growth. Two bacterial endophytic strains were isolated from Solanum nigrum and were identified as Serratia sp. AI001 and Enterobacter sp. AI002 by 16S DNA sequencing. Strains AI001 and AI002, tolerated up to 25 mg/mL Cd in broth culture and showed phosphate solubilization potential in Pikovskaya agar medium. AI001 and AI002 produced indole-3-acetic acid, which was confirmed by gas spectrometry-mass chromatography. Brassica plants stressed with 0, 5, 15, and 25 mg/L Cd showed significant decrease in plant growth, chlorophyll content and biomass, and significant increase in Cd dose-dependent electrolyte leakage. Inoculation of strain AI001 or AI002 significantly enhanced the plant growth attributes of shoot length, root length, chlorophyll content, and biomass as compared to those in uninoculated plants. Reduced glutathione contents in plants stressed with different concentrations of Cd also increased with inoculation of AI001 and AI002. The reason of Cd resistance enhancement in plants by inocula could be due to their greater plant growth promoting activities as well as their antioxidative response.

Overhydration (OH) is a common medical problem found in patients with kidney or heart failure, but still a specific marker has not been found. Clinicians today use bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function like NT-pro-BNP, GFR or creatinine levels. New serum markers such as Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are being researched with promising results. The need to discover a more precise marker of overhydration is dire mainly because physical examination is extremely imprecise. Signs and symptoms of fluid overload like edema or gradual increase of body mass are not always present, especially in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation focusing especially on kidney diseases.

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

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.