L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism during fasting. The wild-type (WT) and LRH-1 liver-specific knockout (LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. During fasting, the LRH-1 LKO mice showed greater accumulation of triglycerides in the liver compared to that in WT mice. Interestingly, LRH-1 LKO liver decreased the perilipin 5 (PLIN5) expression and genes involved in β-oxidation. Additionally, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed to analyze the PLIN5 promoter sequence, which revealed −1620/−1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immuno-precipitation assays. Moreover, fasted WT primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted LRH-1 LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs and manage the cellular needs.

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n=6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.4% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in PFC for [3H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in hippocampus (+9.24%) and PFC (+6.1%) whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin’s antidepressive actions are linked to increased persistent synaptogenesis and possibly also to an acute decrease in 5-HT2AR density.

After the increasing number of SARS-CoV-2 infections all over the world, researchers and clinicians are struggling to find a vaccine or innovative therapeutic strategies to treat this viral infection. The SARS-CoV infection that occurred in 2002, MERS and other more common infectious diseases such as HCV, led to the discovery of many RNA-based drugs. Among them, siRNAs and antisense LNAs have been demonstrated to have effective antiviral effects both in animal models and humans. Owing to the high genomic homology of SARS-CoV-2 and SARS-CoV (80-82%) the use of these molecules could be employed successfully also to target this emerging coronavirus. Trying to translate this approach to treat COVID-19, we analyzed the common structural features of viral 5’UTR regions that can be targeted by non-coding RNAs and we also identified miRNAs binding sites suitable for designing RNA-based drugs to be employed successfully against SARS-CoV-2.

CrHZSM-5 was placed in an electric field with appropriate strength in a quartz packed bed reactor with CO2 as oxidant to analyze its catalytic activity. Olefin yield increases with decrease in band gap since lattice oxygen mobility increases by reducing band gap. Fermi level change at the catalyst surface affects the catalytic activity. One way to change Fermi level is use electric field. In high voltage electric field, energy band was curved, bending of the energy band promoted the activity and Fermi level position is increasing. The CCD experiments were carried out with Design-Expert 7.3 software to determine the interaction between four operating variables, namely: temperature, electrical current, gap distance and metal loading. The levels of the independent variables were: temperature (550-700 °C), electrical current (0-12 mA), gap distance (6-14 mm), metal loading (0.5-7.5 %wt.). The conversion of LPG (Liquefied petroleum gas) was greatly increased by weak and effective application of an electric field to the catalyst bed. The obtained results indicated that the maximum yield value (46.94%) can be achieved under 673.66 °C, input electrical current of 11.01 mA, gap distance of 6.55 mm and metal loading of 3.98 wt.%.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.

Abstract: Composite sintered bodies comprising silicon dioxide (SiO2) nanoparticles dispersed in β-tricalcium phosphate (β-TCP) were prepared. The addition of nano-sized colloidal SiO2 to the β-TCP produced well-dispersed secondary phase nanoparticles that promoted densification by suppressing grain growth and increasing volume shrinkage of the sintered bodies. The SiO2 was found not to react with the β-TCP at 1120 °C and the substitution of silicon for phosphorous to produce a solid solution did not occur. This lack of a reaction is ascribed to the absence of avail-able calcium ions to compensate for the increase in charge associated with this substitution. The SiO2 nanoparticles were found to be present near the intersections of grain boundaries in the β-TCP. A β-TCP composite sintered body containing 4.0 wt% SiO2 exhibited a bending strength comparable to that of cortical bone and hence could potentially be used as a bone filling material.

RCH is known rapidly enhance cold tolerance of insects. Trehalose has been demonstrated to be one of the cryoprotectant in L. oryzophilus, an important invasive pest of rice in China. Trehalose synthesis mainly occurs through the TPS/TPP pathway in insects. In this study, LoTPS gene was cloned and characterized for the first time. Its expression and trehalose content changes elicited by RCH were investigated. Our results revealed that RCH not only increased the survival rate of adults but also upregulated the gene expression level of LoTPS and increased trehalose content under low temperature. We hypothesized upregulated LoTPS promoted trehalose synthesis and accumulation to protect adults from low-temperature damage. To further verify the function of LoTPS gene, we employed RNAi technology. Our findings showed that RCH efficiency disappeared and failed to increase the survival rate when the adults were fed dsRNA of LoTPS. Additionally, inhibiting LoTPS gene expression resulted in no significant difference in trehalose content between RCH and non-RCH treatments. Furthermore, the expression patterns of TRET and TRE were also affected. Collectively, these results indicate the critical role of LoTPS in L. oryzophilus cold resistance after RCH induction. LoTPS can enhance the survival ability by regulating trehalose metabolism. These findings contribute to further understanding of the role of TPS in insect cold resistance and invasiveness of L. oryzophilus. Moreover, RNAi of the LoTPS opens up possibilities for novel control strategies against L. oryzophilus in the future.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

Bone growth plate abnormalities and skull shape defects are seen in hypophosphatasia, a heritable disorder in humans that occurs due to deficiency of Tissue Nonspecific Alkaline Phosphatase (TNAP, Alpl) enzyme activity. Abnormal development of the cranial base growth plates (synchondroses) and abnormal skull shapes have also been demonstrated in global TNAP-/- mice. To distinguish local vs. systemic effects of TNAP on skull development, we utilized P0-Cre to knockout TNAP only in cranial neural crest derived tissues using TNAP flox mice. Here we show that TNAP deficiency in cranial neural crest leads to leads to skull shape defects and deficient growth of the intersphenoid synchondrosis (ISS). ISS chondrocyte abnormalities included increased proliferation in resting and proliferative zones with decreased apoptosis in hypertrophic zones. ColX expression is increased, indicative of premature differentiation in the absence of TNAP. Sox9 expression is increased in both resting and prehypertrophic zones of mutant mice. Expression of PTHrP and IHH were also increased. Finally, cranial base organ culture revealed that inorganic phosphate (Pi) and pyrophosphate (PPi) have specific effects on cell signaling and phenotype changes in the ISS. Together, these results demonstrate that TNAP expression in growth plate chondrocytes is essential for normal development, and that the mechanism likely involves Sox9, PTHrP, IHH and PPi.

Cyanobacteria are photosynthetic microorganisms capable of using solar energy to convert CO2 and H2O into O2 and energy-rich organic compounds, thus enabling sustainable production of a wide range of bio-products. More and more strains of cyanobacteria are identified that show great promise as cell platforms for the generation of bioproducts. However, strain development is still required to optimize their biosynthesis and increase titers for industrial applications. This review describes the most well-known and newest most promising strains available to the community and gives an overview of current cyanobacterial biotechnology and the latest innovative strategies used for engineering cyanobacteria. We summarize advanced synthetic biology tools for modulating gene expression and their use in metabolic pathway engineering to increase the production of value-added compounds, such as terpenoids, fatty acids, and sugars, to provide a go-to source for scientists starting research in cyanobacterial metabolic engineering.

Disrupted nutrient recycling is a significant problem for Europe, while phosphorus and nitrogen are wasted instead of being used for plant nutrition. Mineral phosphate is critical raw material, which contains environmentally hazardous elements such as cadmium and uranium. Therefore, phosphorus recovery from agricultural by-product streams is critically important key priority. Phosphorus recovery from food grade animal bone by-products have been applied researched since 2002 with objective driven evolution progress towards specialized pyrolysis processing technology and animal bone char product (ABC) developments in economical industrial scale. Different animal bone by-products tested under different conditions at 400 kg/h throughput capacity in the continuously operated 3R zero emission autothermal carbonization system. The different material core treatment temperatures (between >300°C and <850°C) were combined with different residence times under industrial productive processing conditions. It has been industrial demonstrated that material core treatment temperature <850°C with 20 minutes residence time is necessary to achieve high quality ABC with useful agronomic value. The output ABC product having concentrated >30% phosphorus pentoxide (P2O5) and specific quality innovative fertilizer for agronomical efficient organic and low input farming applications as functional organic fertilizer, soil improver, growing medium and/or fertilizing product blend with high mineral phosphate fertiliser replacement value.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

In the realm of the five-category classification endeavor, there has been limited exploration into applied techniques for classifying Arabic text. These methods have primarily leaned on singletask learning, incorporating manually crafted features that lack robust sentence representations. Recently, the Transformer paradigm has emerged as a highly promising alternative. However, when these models are trained using single-task learning, they often face challenges in achieving outstanding performance and generating robust latent feature representations, especially when dealing with small datasets. This issue is particularly pronounced in the context of the Arabic dialect, which has a scarcity of available resources. Given these constraints, this study introduces an innovative approach to dissecting sentiment in Arabic text. This approach combines Inductive Transfer (INT) with the Transformer paradigm to augment the adaptability of the model and refine the representation of sentences. By employing self-attention SE-A and feed-forward sub-layers as a shared Transformer encoder for both the five-category and three-category Arabic text classification tasks, this proposed model adeptly discerns sentiment in Arabic dialect sentences. The empirical findings underscore the commendable performance of the proposed model, as demonstrated in assessments of the Hotel Arabic-Reviews Dataset, the Book Reviews Arabic Dataset, and the LARB dataset.

Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modelled by administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo, or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102), but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations.

Cannabidiol, is the first cannabis-derived drug approved for the treatment of Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). The current study performed a descriptive analysis followed by a disproportionality analysis of potential adverse events caused by CBD extracted from the database VigiBase®. Further, biological plausibility of the association between CBD and the serotonin 5-HT1A receptor, as possible cause of adverse events was analyzed and discussed. Data were extracted from VigiBase® database using VigiLyze® signal detection and signal management tool. Adverse events in VigiBase® reports were coded using MedDRA, version 19 of Preferred Terms (PTs). Data were uploaded into SPSS software and analyzed via disproportionality analysis. Statistically significant disproportionality signals for CBD were found for “weight decreased” 5.19 (95% CI: 4.54 - 5.70), “hypophagia” 3.68 (95% CI: 3.22 - 5.27), and “insomnia” 1.6 (95% CI: 1.40 - 1.83). Positive IC025 values were found for “weight decreased” (2.2), “hypophagia” (1.3), and “insomnia” (0.5), indicating a surplus of reported cases. CBD’s interactions with 5-HT1A serotonin receptors may offer a potential biological explanation for the occurrence of insomnia in patients. It is noteworthy that the risk profiles mentioned in the prescribing information for CBD as antiepileptic agent by regulatory agencies showed disparities specifically related to the adverse event “insomnia”.

Background: The presence of single nucleotide polymorphisms in the gene encoding key en-zyme in the folate pathway methyltetrahydrofolate reductase (MTHFR), causes methylation disorders associated with CAD development. Methods: Study group: 42 patients with CAD con-firmed by coronary angiography. Controls: 16 patients without CAD symptoms or significant coronary artery stenosis, based on invasive coronary angiography or multislice computed to-mography with coronary artery calcification scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined by LC-MS. Results: c.[1286A>C];[1286A>C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to (CAD-) cohort and to the European population. The con-centration of 5-MTHF and folic acid in the subgroups of patients with methylation disorders di-vided by genotypes and (CAD+) was lower compared to (CAD-). Conclusions: The homozygous c.1286 A>C MTHFR variant can be considered as CAD genetic marker. In the subjects with the c.1286 A>C heterozygous and homozygous genotypes, lower concentrations of methyltetrahy-drofolate (5-MTHF) were observed. 5-MTHF can be considered as a biomarker of CAD. Identifi-cation of people at high risk of CAD using genetic tests can contribute to personalized therapy using active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymor-phisms.

In the face of the current energy and environment problems, the full use of biomass resources instead of fossil energy to produce a series of high-value chemicals has great application prospects. 5-hydroxymethylfurfural (HMF), which can be synthesized from lignocellulose as raw material, is an important biological platform molecule. Its preparation and catalytic oxidation of subsequent products have important research significance and practical value. In the actual production process, porous organic polymer (POPs) catalysts are highly suitable for biomass catalytic conversion due to its high efficiency, low cost, good designability, and environmentally friendly features. Here, we briefly described the application of various types of POPs (including COFs、PAFs、HCPs、CMPs) in the preparation and catalytic conversion of HMF from lignocellulosic biomass, and analyzed the influence of the structural properties of catalysts for the catalytic performance. Finally, we summarized some challenges that POPs catalysts will face in biomass catalytic conversion, and prospected the important research directions in future. This review would provide valuable references for the efficient conversion of biomass resources into high-value chemicals in practical applications.

Synthesis of ZSM-5 zeolite from OSDA-free systems has been a very interesting alternative method because it can avoid the usage of organic templates and consequent calcination step. However, in opened reports, organic substance such as alcohol is more or less involved. In the present work, a calcined commercial ZSM-5 zeolite was used as a seed, sodium aluminate as an aluminum source, silica sol as a silicon source, which ensures that there is no any organics (template) in the synthesis system, and polycrystalline ZSM-5 aggregates consisting of rod-like nanocrystals are successfully prepared in a completely OSDA-free system. The effects of seed (chemical component, dosage) and crystallization conditions on the synthesis of ZSM-5 were systematically investigated. The results show that highly crystallinity ZSM-5 aggregate consisting of primary nano-sized crystals with a size of less than 100 nm can be yielded from a gel precursor with 5.6 wt.% seed after hydrothermal treatment for 48 h. The results also shows that the chemical composition of the seeds had little effect on the topological structure and pore structure of the synthesized samples, but the seed with a low Si/Al ratio is more conducive to the rapid crystallization of zeolite and to the improvement of the acid, especially the strong acid centers of the catalyst.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

A new variant of the SARS-CoV-2 Omicron BA.5 virus has displaced all previous variants of the virus around the world. Preliminary assessment of the effectiveness of drugs for the prevention and treatment of COVID-19 requires the availability of infection models in animals. In this study, we characterize the infection model SARS-CoV-2 Omicron BA.5 and its progeny sublineage BE.1 in hACE2-transgenic mice and in Syrian hamsters. Both sublineages turned out to be pathogenic for animals – the challenged animals showed weight loss, a high level of viral load and acute inflammation in the lungs. Part of BA.5-infected mice died after virus challenge, indicating that this virus variant is more pathogenic than the previous BA.1 variant but less pathogenic than Wuhan variant.

CRISPR-Cas allows us to introduce desired genome editing, including mutations, epitopes, and deletions with unprecedented efficiency. The development of CRISPR-Cas has progressed to such an extent that it is now applicable in various fields with the help of model organisms. C. elegans is one of the pioneering animals in which numerous CRISPR-Cas strategies have been rapidly es-tablished over the past decade. Ironically, the emergence of numerous methods makes the right choice of method difficult. Choosing an appropriate selection or screening approach is the first step in planning a genome modification. This report summarizes the key features and applications of CRISPR-Cas methods using C. elegans and illustrates key strategies. Our overview of significant advances in CRISPR-Cas will help readers to understand current advances in genome editing and navigate various methods of CRISPR-Cas genome editing.

This study focused on the impact of the treatment with the hypomethylating agent 5-Azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD, catalase, CAT, glutathion peroxidase, GPx, and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, and CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, and increased CAT activity compared with healthy subjects, with not changes in SOD, GPx and GRd activities, and AOPP levels. When analyzed the evolution from early- to advanced stages of the disease, the GPx activity, GSSG/GSH ratio, LPO and AOPP increased, with a reduction in CAT. GPx changes were related with the presence of risk factors such as high-risk IPSS-R or mutational score. Besides, there was an increase in IL-2, IL-6, IL-8 and TNF-α plasma levels, with further increase of IL-2 and IL-10 from early to advanced stage of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generates oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

The COVID-19 pandemic and associated restrictive measures implemented may considerably affect people’s lives. This study aimed to assess the well-being of Vietnamese people after COVID-19 lockdown measures were lifted and life gradually returned to normal. An online survey was organized from 21st to 25th April 2020 among Vietnamese residents aged 18 and over. Besides collecting socio-demographic and COVID-19-related data, the WHO-5 Well-Being Index (scored 0–25) was used to score participants’ well-being. A multivariate logistic regression model was used to determine the predictors of well-being. A total of 1922 responses were analyzed (mean age: 31 years; 30.5% male). Mean well-being score was 17.35±4.97. Determinants of high well-being score (≥13) included older age, eating healthy food, practising physical exercise, working from home, and adhering to the COVID-19 preventive measures. Female participants, persons worried about their relatives’ health, and smokers were more likely to have a low well-being score. In conclusion, after the lockdown measures were lifted, the Vietnamese people continued to follow COVID-19 preventive measures and most of them scored high on the well-being scale. Waiting to achieve large scale COVID-19 vaccine coverage, promoting preventive COVID-19 measures remains important, together with strategies to guarantee the well-being of the Vietnamese people.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

Characterised by the growth of benign tumours, fibropapillomatosis (FP) is a debilitating disease that predominantly afflicts the endangered green turtle (Chelonia mydas). A growing body of histological and molecular evidence has consistently associated FP tumours with Chelonid alphaherpesvirus 5 (ChHV5), leading this virus to be considered the most likely aetiological agent of FP. However, a recent study which detected both ChHV5 and Chelonia mydas papillomavirus 1 (CmPV1) DNA in FP tumour tissues has challenged this hypothesis. The present study aimed to establish the wider prevalence of CmPV1 and co-occurrence with ChHV5 in marine turtles in waters adjacent to the east coast of Queensland, Australia. This comprehensive molecular survey screened a total of 353 samples from 275 foraging turtles using probe-based qPCR. Three sample categories were used in this study: Group A (FP tumours), Group B (non-tumoured skin from turtles with FP tumours) and Group C (non-tumoured skin from turtles without FP tumours). Concurrent detection of ChHV5 and CmPV1 DNA is reported for all three categories, with the highest rate of concurrent detection reported for Group A samples (43.5%). Collectively, these results pivot the way we think about FP; as an infectious disease where two separate viruses may be at play.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

A supramolecular host-guest interaction and sensing between cationic pillar[5]arenes (CP5) and L-carnitine were developed by the competitive host-guest recognition for the first time. The fluorescence sensing platform was constructed by CP5 functionalized Au nanoparticles (PP5@Au-NPs) as receptor and probe (rhodamine 123, R123), which shown a high sensitivity and selectivity to L-carnitine detection. Due to the property of the negative charge and molecular size of L-carnitine, it can be highly captured by the CP5 via electrostatic interactions and hydrophobic interactions. The mechanism of host-guest between PP5 and L-carnitine was studied by ¹H NMR and molecular docking, which indicated more affinity binding force of PP5 with L-carnitine. Therefore, a selective and sensitive fluorescent method was developed. It has a linear response of 0.1–2.0 and 2.0–25.0 μM and a detection limit of 0.067 μM (S/N = 3) for L-carnitine. The fluorescent sensing platform was also used to detect L-carnitine in human serum and milk samples, which provided potential applications of detection drugs of abuse, and had path for guarding a serious food safety issues.

Today, non-expensive remote sensing (RS) data from different sensors and platforms can be obtained at short intervals and be used for assessing several kinds of forest characteristics at the level of plots, stands and landscapes. Methods such as composite estimation and data assimilation can be used for combining the different sources of information to obtain up-to-date and precise estimates of the characteristics of interest. In composite estimation a standard procedure is to assign weights to the different individual estimates inversely proportional to their variance. However, in case the estimates are correlated, the correlations must be considered in assigning weights or otherwise a composite estimator may be inefficient and its variance be underestimated. In this study we assessed the correlation of plot level estimates of forest characteristics from different RS datasets, between assessments using the same type of sensor as well as across different sensors. The RS data evaluated were SPOT-5 multispectral data, 3D airborne laser scanning data, and TanDEM-X interferometric radar data. Studies were made for plot level mean diameter, mean height, and growing stock volume. All data were acquired from a test site dominated by coniferous forest in southern Sweden. We found that the correlation between plot level estimates based on the same type of RS data were positive and strong, whereas the correlations between estimates using different sources of RS data were not as strong, and weaker for mean height than for mean diameter and volume. The implications of such correlations in composite estimation are demonstrated and it is discussed how correlations may affect results from data assimilation procedures.

Sphingosine 1-phosphate (S1P) is a signaling lipid molecule involved in various cellular processes. It is important to develop a quantitative method for S1P to determine endogenous levels and to investigate its functions. Especially since S1P is a tiny lipid component of most biological samples, highly sensitive analysis by LC-MS/MS is required. The main challenge in S1P analysis by chromatography is peak broadening due to the presence of a polar phosphate and zwitterion formation in S1P. In this study, we used hydrogen fluoride (HF) to efficiently remove a phosphate and then analyzed the surrogate, sphingosine, as a sharp peak by LC-ESI-MS/MS. We optimized the dephosphorylation reaction in terms of reaction time, temperature, and HF concentration. Multiple reaction monitoring (MRM) for dephosphorylated form of S1P and C17-S1P as internal standard at m/z transition 300.4&gt;282.4 (quantification ion), 300.4&gt;262.4 (qualification ion), 286.3&gt;268.2 (internal standard). This method was validated by essential parameters such as specificity, linearity, range, LOQ, LOD, accuracy, precision, and repeatability. To confirm this new method, we quantified S1P levels in various serum products (100.02 ~ 284.38 nM). To apply the method in vivo, we analyzed S1P in plasma and kidney tissues obtained from a chronic kidney disease (CKD) mouse model. S1P levels were increased only in CKD kidney tissue but not in plasma. In conclusion, by applying the dephosphorylation step with HF, we established a new sensitive LC-MS/MS quantitative method for S1P that can be applied to biological samples.

Ceramic samples based on b-calcium pyrophosphate b-Ca2P2O7 were prepared using firing at 900, 1000, and 1100 oC from powders of g-calcium pyrophosphate g-Ca2P2O7 with preset molar ratios Ca/P=1; 0,975 and 0,95. To prepare powders of g-calcium pyrophosphate g-Ca2P2O7 with preset molar ratio Ca/P=1; 0,975 and 0,95 powder mixtures based on calcium lactate pentahydrate Ca(C3H5O3)2⋅5H2O and, monocalcium phosphate monohydrate Ca(H2PO4)2⋅H2O were treated in an aqua medium in mechanical activation conditions, dried, disaggregated in acetone, and heat-treated at 600 oC. The phase composition of powder mixtures after treatment if planetary mill in aqua medium included both brushite CaHPO4⋅2H2O or monetite CaHPO4, and starting salts. The phase composition of all powder mixtures after disaggregation in acetone in planetary mill included monetite CaHPO4 and starting salts. After heat treatment at 600 oC according to the XRD data phase composition of all powder mixtures was presented by g-calcium pyrophosphate g-Ca2P2O7. The grain size of ceramics increased both with the growth of firing temperature and with decreasing of molar ratio Ca/P of powder mixtures. Calcium polyphosphate (t melt =960–968 oC) formed from monocalcium phosphate monohydrate Ca(H2PO4)2⋅H2O acted like a liquid phase sintering additive. It was confirmed by tests in vitro, that prepared ceramic materials with preset molar ratio Ca/P=1; 0,975 and 0,95 and phase composition presented by b-calcium pyrophosphate b-Ca2P2O7 according to XRD data were biocompatible and could maintain bone cells proliferation.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p&lt;0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Dentin bonding is a key in restorative dentistry. Herein, we developed self-etching two-bottle adhesive system containing 10-methacryloyloxidecyl dihydrogen phosphate monomer (MDP) and the physical, mechanical, and biocompatible properties were evaluated. The characteristics of MDP were analyzed using nuclear magnetic resonance (NMR). The water sorption and solubility, the shear-bond strengths to dentin and enamel, and cytotoxicity tests were performed. The newly blended experimental group showed the lowest thickness and water sorption and solubility values. The shear bond strength to enamel and dentin were comparable to control groups (the three other products) all test groups showed 60% of cell viability. In this study, the properties of the newly synthesized adhesive are comparable with the others. The fundamental goal of this study is to get the MDP patent released, as it is intended for domestic production. For this purpose, this dentin adhesive was developed and compared with the commercial product.

The problem of effective immobilization of liquid radioactive waste (LRW) is key to the successful development of nuclear energy. The possibility of using magnesium potassium phosphate (MKP) compound for LRW immobilization on the example of nitric acid solutions containing actinides and rare earth elements (REE), including high level waste (HLW) surrogate solution is considered in the research work. Under the study of phase composition and structure of the MKP compounds obtained by the XRD and SEM methods, it was established that the compounds are composed of crystalline phases - analogues of natural phosphate minerals (struvite, metaankoleite). The hydrolytic stability of the compounds was determined according to the semi-dynamic test GOST R 52126-2003. Low leaching rates of radionuclides from the compound are established, including a differential leaching rate of ²³⁹Pu and ²⁴¹Am - 3.5 × 10^-7 and 5.3 × 10^-7 g/(cm²∙day). As a result of the research work it was concluded that the MKP compound is promising for LRW immobilization and can become an alternative material combining the advantages of easy implementation of the technology like cementation and the high physical and chemical stability corresponding to a glass-like compound.

The reaction between 5-acetylbarbituric acid and 4-dimethylthiosemicarbazide or 4-hexamethyleneiminyl thiosemicarbazide produces 5-acetylbarbituric-4-dimethylthiosemicarbazone (H2AcbDM) and 5-acetylbarbituric-4N-hexamethyleneiminyl thiosemicarbazone (H2Acbhexim). Eight new complexes with different cooper (II) salts have been prepared and characterized using elemental analysis, molar conductance, UV–vis, ESI-HRMS, FT-IR, magnetic moment, EPR and cyclic voltammetry. In addition, three-dimensional molecular structures of [Cu(HAcbDM)(H2O)2](NO3)·H2O (3a), [Cu(HAcbDM)(H2O)2]ClO4 (4), and [Cu(HAcbHexim)Cl] (6) were determined by single crystal X-ray crystallography, and was carried out an analysis of their supramolecular structure. The H-bonded assemblies were further studied energetically using DFT calculations, MEP surface and QTAIM analyses. In these complexes, the thiosemicarbazone coordinates to the metal ion in an ONS-tridentate manner, in the O-enolate/S-thione form. The electrochemical behavior of the thiosemicarbazones and their copper(II) complexes has been investigated at room temperature using the cyclic voltammetry technique in DMFA. The Cu(II)/Cu(I) redox system was found to be consistent with the quasi-reversible diffusion-controlled process.

With the inclusion of Internet Gaming Disorder (IGD) in both the DSM-5 and ICD-11, understanding the prevalence and diagnostic discrepancies is crucial for developing appropriate interventions. This study presents a meta-analysis of the prevalence of IGD based on two diagnostic criteria. We systematically searched PubMed, Web of Science databases. 17 studies were included in the final analysis, The analysis incorporated studies employing the DSM-5 and ICD-11 criteria and focused on the impact of various factors, including study location, sample size, and quality score, on the reported prevalence rates using a random-effects model. Heterogeneity and publication bias were analyzed using an I2 test and Galbraith plots , The prevalence of IGD varied among the selected studies, with a general pooled prevalence of 5% (95% CI: 3%–7%). Subgroup analysis indicated that the prevalence rates of IGD (DSM-5 criteria) and GD (ICD-11 criteria) do not show significant differences. DSM-5-based scales yielded varied results, while heterogeneity among the studies was high (I2 = 98.50). In contrast, ICD-11-based scales produced more consistent and less variable findings. Our findings highlight that assessment scales, not diagnostic criteria, impact IGD prevalence. This underscores the importance of adopting standardized methodologies to guide public health interventions. However, given the limited research based on ICD-11 diagnostic criteria, further investigation is necessary to determine the variations in prevalence rates of IGD under different diagnostic standards.

This report provides a comprehensive overview of occupational asthma and respiratory hypersensitivity, focusing on some chemicals used in the workplace Includes numerous case studies and research papers related to occupational exposure methacrylates, such as HEMA-HPMA, and respiratory hypersensitivity are discussed And the relationship is explored The book also examines asthma pathophysiology, emerging drug delivery systems used to treat asthma, and the potential of nanoparticles , dendrimers and micellar systems have to improve pulmonary drug delivery in detail The worldwide prevalence of asthma is highlighted, with higher rates in high-GDP countries. The book highlights the need to improve asthma diagnosis, treatment and biomarkers, particularly in rural and low-income countries where the disease is often underdiagnosed and inadequately treated, and discusses the role of inflammation in asthma, in particular secondary inflammation characterized by specific cytokines and inflammation cells In addition, the paper explores various drug delivery methods, such as parenteral and parenteral drugs, pressurized inhalers (pMDIs), dry powder inhalers ( DPIs), nebulizers, nanoparticles, liposomes, micellar systems, microparticles , dendrimers, and gene therapy . These systems aim to increase pulmonary delivery of drugs and improve clinical outcomes. The potential of dendrimer bilirubin-based nanoparticles and micellar systems in the treatment of asthma and lung inflammatory diseases, including asthma, has been discussed in summary, this paper provides an overview of occupational asthma and respiratory hypersensitivity, and this discussion highlights the association between methacrylate exposure and respiratory hypersensitivity.

Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with in-gested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant to help evaluate potential effects of ingested jet fuel. Results of the in vivo study provided evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), indi-cations of abnormal estrous cycles, and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while the alternative jet fuel derived from the camelina plant was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid re-ceptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

The intricacies of translational strategies make this stage of the implementation of genetic information one of the most difficult to understand and, at the same time, perhaps the most interesting. It also becomes clear that all this variety of strategies is not just a consequence of a long evolutionary history but is of paramount importance for fine-tuning gene expression and metabolic modulation. This is especially true for those organisms that demonstrate predominantly biochemical and physiological reactions with a lack of behavioural ones. Plants are just such a group of organisms. Overcoming unfavourable environmental conditions occupies a key place in plant physiology. This is especially true with the changing conditions of global warming and the irretrievable loss or depletion of natural ecosystems. Conceptually, the response of plants to abiotic stress is a set of complex and intricate strategies. This is dictated both by a variety of abiotic factors that provoke stressful conditions and by a variety of molecular genetic mechanisms that make it possible to fine-tune the metabolic pathways through which the plant organism overcomes non-standard and non-optimal conditions. In the presented review, we tried to focus on the state-of-the-art in the field of translational regulation in plants under abiotic stress conditions. Various regulatory elements and patterns are considered in relative chronological order. We also considered it necessary to pay attention to key high-performance methods for studying the dynamics of genetic information at the stage of translation.

Jacobian theta function identities are related to the Addition formula for the Weierstrass 1 Sigma function. In this paper, from the Addition formula for Weierstrass Sigma function, new and 2 simple proofs of four square sums theorem are given. Using the addition formula of the theta func- 3 tions, we also give simple proofs of two square sums and eight square sums theorem.

Purpose The COVID-19 pandemic, triggered by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in over 160 million infections and 3.5 million fatalities worldwide. Evidence of SARS-CoV-2 presence in the highly vascularized penile tissue and the established correlation between COVID-19 and subsequent erectile dysfunction (ED) has emerged. Robot-assisted radical prostatectomy (RARP) is a popular procedure for prostate cancer because of its reliability and swift recovery rate. However, the ED prevalence post-surgery is believed to be comparable to open surgery, and postoperative ED significantly affects the patient's quality of life. Our study aimed to explore the effect of COVID-19 on ED recovery in patients undergoing bilateral nerve preservation during RARP. Materials and Methods We conducted a retrospective study on 85 patients who underwent bilateral nerve-sparing RARP (nsRARP) at our institution between December 2017 and May 2021. Chart reviews and the International Index of Erectile Function-5 (IIEF-5) questionnaire facilitated the analysis. Our objective was to contrast ED recovery after surgery between SARS-CoV-2–infected and non-infected patients using preoperative IIEF-5 scores and scores at 6, 12, and 24 months post-surgery. We defined successful ED recovery as an IIEF-5 score of 17 or higher and successful sexual intercourse. We also compared ED recovery rates between the two groups, regardless of the timing of COVID-19 diagnosis. IBM's SPSS version 18.0 assisted in the statistical analysis, with Fisher's exact test and chi-square test used for comparing categorical variables. Independent t-tests determined mean differences between baseline and postoperative IIEF-5 scores. A p-value less than 0.05 was considered statistically significant. Results From December 2017 to May 2021, our institution executed 213 RARP cases, with 185 of these involving nerve preservation. Among these patients, 133 had an IIEF-5 score of 17 or higher during preoperative EF assessment. We included 85 patients with consistent IIEF-5 records before surgery and at 6, 12, and 24 months post-surgery in this study. Of these, 44 and 41 patients comprised the COVID-19–positive and COVID-19–negative groups, respectively. The COVID-19–positive group had a higher proportion of diabetes mellitus (DM) patients (24 (54.55%) vs. 7 (17.07%), p<0.001). There was no significant difference in preoperative IIEF-5 scores or scores up to 6 months after surgery between the two groups. However, the IIEF-5 scores of the COVID-19–positive group were statistically lower after 12 and 24 months post-surgery. Additionally, the COVID-19–negative group showed a more considerable score increase between 6 and 12 months post-surgery, and the EF recovery rate was lower in the COVID-19–positive group starting from the 12th month after surgery. Within the COVID-19–positive group, no statistically significant difference in IIEF-5 scores was found between single infection and multiple reinfection groups. Conclusions Principal component analysis revealed the impact of COVID-19 on ED recovery in patients who underwent nsRARP. The most substantial changes in IIEF-5 scores occurred between 6 and 12 months. From 12 months onwards, the COVID-19–positive group had significantly lower scores, and fewer patients had IIEF-5 scores above 17. However, the number of COVID-19 diagnoses did not significantly affect the IIEF-5 scores.

Depressive disorder is a disease that causes a decrease in daily function, and the prevalence of depressive disorder in Korea is the highest among OECD countries. However, due to lack of manpower and negative social awareness, timely treatment is not being performed properly. As a solution to this, AI counseling chatbots are emerging, and it is essential to use labeled datasets to create chatbots. Currently, many countries around the world, including Korea, use the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, DSM-5, but there are no nine labeled datasets according to the DSM-5 depression disorder diagnosis criteria. This study collects sympathetic datasets, analyzes morphemes using Kind Korean Morpheme Analyzer and augments and builds a word dictionary using Word2Vec. As a result, we have labeled the dataset with nine criteria for diagnosing DSM-5 depressive disorder, which will enhance the performance of the counseling chatbot.

The presence of azo dyes in textile effluents is an issue of major concern due to their potential impact on the environment and human health. In this study we investigate the photocatalytic degradation under visible light of Reactive Violet 5 (RV5), an azo dye widely used in the textile industry. A preliminary screening of different titania-based catalysts was carried out to identify the best candidate for RV5 removal. The selected catalyst was then tested in a stirred and aerated lab-scale reactor illuminated with a light LED source (λmax = 460 nm). The effects of pH, catalyst load and hydrogen peroxide additions on the efficiency of dye removal were evaluated. Under the best conditions (pH 10, 3 g/L of catalyst and 60 mM hydrogen peroxide), the dye solution was completely decolorized in about 2 h. Overall, the results obtained suggest that the proposed process may represent a suitable method for the removal of RV5 from textile effluents.

In the past decade, under the background of the carbon peaking and carbon neutrality era, the rapid development of new energy vehicles has put forward higher requirements for the performance of strike forces such as battery cycle life, energy density and cost. Lithium-ion batteries have gradually become the mainstream of electric vehicle power batteries due to their excellent energy density, rate performance and cycle life. At present, the most widely used cathode materials for power batteries are lithium iron phosphate (LFP) and ternary nickel-cobalt-manganese (NCM). However, these materials exhibit the bottlenecks that limit the improvement and promotion of power battery performance. In this review, the performance characteristics, cycle life attenuation mechanism (including structural damage, gas generation and active lithium loss, etc.) and improvement methods (including surface coating and element-doping modification) of LFP and NCM batteries are reviewed. Finally, the development prospects of this field are proposed.

Endophytic fungi colonize the inner tissues of plants and provide direct and indirect benefits to the plant. Although Mongolia is rich in medicinal plants, due to climatic and anthropogenic reasons the resources are being depleted and many species are under the threat of gradual extinction, while the endophytic fungi of Mongolian plants are largely unknown. Understanding the diversity and metabolic potential of endophytic fungi is of great significance in terms of the utilization of beneficial fungal strains in plant propagation and the discovery of bioactive compounds. In this study, a total of 24 culturable endophytic fungal strains were isolated from Cynomorium songaricum (Rupr.), a medicinal and vulnerable plant species of Mongolia. Based on the morphological characteristics and the sequences of the rDNA internal transcribed spacer (ITS) region, the isolates were identified to 6 genera: Fusarium (8), Clonostachys (7), Penicillium (6), Alternaria (1), Aspergillus (1), and Madurella (1). The antimicrobial activity was assessed by agar-diffusion method, revealing that 15 strains were able to inhibit the growth of at least one of the test organisms. Among them, 1 strain showed inhibitory activity against Escherichia coli, 12 against Bacillus subtilis, 13 against Staphylococcus aureus, 8 against Aspergillus niger, respectively. All fungal strains were screened for their ability to solubilize complex phosphorus and zinc minerals and for their production of indole-3-acetic acid (IAA). The strains were preserved in the national culture collection for further sustainable exploitation of their biotechnological potential.

Lucky bamboo (Dracaena sanderiana hort. ex Mast. = Dracaena braunii) is a domestic species widely cultivated for ornamental purposes in China. In March 2022, a severe occurrence of anthracnose disease was observed on the stems of lucky bamboo plants in a greenery retail store located in Nanjing, Jiangsu Province, China. The morphological characteristics of isolates obtained from diseased stem tissues were identical with those described for Colletotrichum species. Based on multilocus phylogenetic analysis with the internal transcribed spacer (ITS), actin (ACT) gene, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, the pathogen was identified as Colleto-trichum gloeosporioides (Penz.) Penz. & Sacc. Pathogenicity was verified by mycelial plug-inoculating stem cuttings of one-year-old lucky bamboo plants and spray-inoculating whole one-year-old lucky bamboo plants, respectively. Koch’s postulates were fulfilled by the re-isolation of C. gloeosporioides from symptomatic tissues. To the best of our knowledge, this report describes the first time that C. gloeosporioides was observed to cause anthracnose on lucky bamboo in China.

Endophytic microbes are a ubiquitous group of plant-associated communities that colonize the intercellular or intracellular host tissues while giving numerous beneficial effects to the plants. All the plant species are thought to be associated with endophytes, majorly constituted with bacteria and fungi. During the last two decades, there has been a considerable movement toward the study of endophytes associated with coffee plants. In this review, the main consideration is given to address the coffee-associated endophytic bacteria and fungi, particularly their action on plant growth promotion and the biocontrol of pests. In addition, we sought to identify and analyze the gaps in available research. Additionally, the potential of endophytes to improve the quality of coffee seeds is briefly discussed. Even though there are limited studies on the subject, it has been well recognized the potentiality of coffee endophytes in plant growth promotion through enhancing nitrogen fixation, availability of minerals, nutrient absorption, secretion of phytohormones, and other bioactive metabolites. Further, the antagonistic effect against various coffee pathogenic bacteria, fungi, nematodes, and also insect pests lead to the protection of the crop. Furthermore, it is recognized that endophytes enhance the sensory characteristics of coffee as a new field of study.

In Nitrate Vulnerable Zones (NVZ) site-specific techniques are needed to match N availability with durum wheat (Triticum turgidum subsp. durum Desf.) requirements. Enhanced-efficiency fertilizers (EEF) can improve efficient N supply and reduce leaching, thus contributing to sustainable agriculture. To study the effects of rates, sources and timings of nitrogen application, two-year field experiments were carried out at two Mediterranean NVZs of Central Italy (Pisa and Arezzo). The trial compared: i) two N rates: one based on the crop N requirements (NO), the other on the Action Programmes’ prescriptions of the two NVZ (NAP); ii) three N sources (urea, methylene urea (MU), and nitrification inhibitor (NI) 3,4-Dimethylpyrazole phosphate (DMPP); and two top-dressing timings (1st tiller visible and 1st node detectable). Grain yield and yield components were determined, together with N uptake. Results showed that: i) grain and biomass production were reduced with NAP at both locations; ii) urea performed better than slow-release fertilizers; iii) the best application time varied depending on N source and location: at Pisa enhanced-efficiency fertilizers achieved higher yields when applied earliest, while for urea the contrary was true; at Arezzo different N fertilizers showed similar performances between the two application timings. Different behaviors of top-dressing fertilizers at the two localities could be related to the diverse patterns of temperatures and rainfall. Therefore, optimal fertilization strategies vary according to environmental conditions.

The aim of this study was to determine the microbial stability, challenge to L. monocytogenes, and some physicochemical properties of turkey breast meat by alginate-based coating enriched with postbiotics (8% concentration, CFS) of Bifidobacterium bifidum DSM 20456 and Bifidobacterium bifidum BB12 strains. For this purpose, firstly, some antimicrobial and total phenolic matter, flavonoid, and DPPH activity values of postbiotics were determined. In addition, FTIR analysis was performed to see the intermolecular interactions of the biological coating agent. As a result of the study, alginate solution with postbiotic showed significant differences in pH, a*, b*, yeast-mold values of turkey meat during storage (7 days), while L* value, total aerobic mesophilic bacteria count (TMAP), psychrotrophic bacteria (PAB), lactic acid bacteria (LAB) and Listeria monocytogenes count were not effective (p&gt;0.05).

(1) Background: The aim of study was to investigate the salt consumption by children and adolescents from the Silesian Province (Poland), taking into account the region’s dietary traditions and number of years of school education. (2) Methods : 300 students aged 10–18 from different types of schools, were enrolled in the study and divided into groups in terms of: school, sex, the state of nutrition. The survey questionnaire about dietary habits, including the frequency and serving size with respect to 12 salty products was used. On the basis of the frequency and the amount of consumed products, as well as the data on salt content, the amount of total daily intake of salt was estimated.; (3) Results: The mean daily intake of salt by children and adolescents was 1.083 g ( 0.433 g of sodium); children aged 10–12 consumed the highest amount of salt (1.296 g/day) compared to pupils aged 13–15 (1.131 g of sodium) and adolescents aged 16–18 (0.863 g/day); (4) Conclusions: With age, as a result of various factors, the consumption of salt declines. The parents impact and the familial socio-environmental factors begin to wane, and other factors start to have influence, e.g. school education of healthy lifestyle, health behavior of peers.

Results showed that mulberry leaves could significantly reduce backfat thickness (P&lt;0.05) and increase intramuscular fat (IMF) content (P&lt;0.05). Lipidomics analysis showed that mulberry leaves improved lipid profile composition and increased the proportion of triglycerides (TG). Interestingly, IMF content was positively correlated with acyl C18:2 and negatively correlated with C18:1 of differential TGs. In addition, cecal microbiological analysis showed that mulberry leaves could increase the abundance of bacteria such as UCG−005, Muribaculaceae_norank, Prevotellaceae_NK3B31_group, Limosilactobacillus, and so on. At the same time improve the L-tyrosine-baton rouge ester, Oleic acid methyl ester, 21-deoxycortisol, N-acetyldihydrosphingosine, Mulberrin relative abundance. In this study, we found that mulberry leaves could extremely significantly increasing the mRNA relative expression of lipoprotein lipase (LPL), fatty acid-binding protein 4 (FABP4) and peroxisome proliferators-activated receptor γ (PPARγ) in muscle (P＜0.01), significantly increasing mRNA relative expression of diacylglycerol acyltransferase 1 (DGAT1) (P＜0.05) and significantly decreasing the mRNA relative expression of acetyl CoA carboxylase (ACC) (P＜0.05), and aignificantly upregulated hormone-sensitive triglyceride lipase (HSL), peroxisome proliferators-activated receptor α (PPARα) mRNA relative expression (P＜0.05) in backfat. In addition mulberry leaves could increased serum leptin and adiponectin (P＜0.01). Ultimately lead to up-regulation of IMF and down-regulation of backfat.

This paper explores the ethical considerations surrounding the research on echinoderms, a group of invertebrates that has recently garnered attention in the scientific community. We emphasize the importance of responsible animal handling and the need for an ethical framework that encompasses echinoderms. The 3R's principle, advocating for the replacement of conscious living vertebrates with non-sentient material in research, is discussed as a guiding tool in current animal research practices. As invertebrates are generally classified as non-sentient animals, the Replacement dimension tends to favor them as prevalent models in experimental research. While we currently lack the means to assess the mental states of invertebrates, there is undeniable evidence of social behavior in many species, suggesting that a lack of interactions with these organisms could potentially adversely affect their well-being. In the last few years, considerable progress has been made in developing an ethical framework that takes invertebrates into account, particularly cephalopods, crustaceans, and echinoderms. In this context, we discuss the development of a broader conceptual framework of 5R’s that includes Responsibility and Respect, which may guide practices ensuring welfare in echinoderms, even in the absence of any particular normative.

The vascular endothelium is key target for immune, and thrombotic responses that has to be controlled in successful xenotransplantation. Several genes were identified that if induced or overexpressed help to regulate the inflammatory response and preserve the transplanted organ function and metabolism. However, few studies addressed combined expression of such genes. The aim of this work was to evaluate in vivo the effects of the simultaneous expression of a three human genes in a mouse generated using the multi-cistronic F2A technology. Male 3-month-old mice that express human heme oxygenase 1 (hHO-1), ecto-5’-nucleotidase (hE5NT), and ecto-nucleoside triphosphate diphosphohydrolase 1 (hENTPD1) (Transgenic) were compared to wild-type FVB mice (Control). Background analysis include extracellular nucleotide catabolism enzymes profile on the aortic surface, blood nucleotide concentration and serum L-arginine metabolites. Furthermore, inflammatory stress induced by LPS in transgenic and control mice was used to characterize interleukin 6 (IL-6) and adhesion molecules endothelium permeabil-ity responses. Transgenic mice had significantly higher rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis on the aortic surface in comparison to control. Increased levels of blood AMP and adenosine were also noticed in transgenics. Moreover, transgenic ani-mals demonstrated the decrease in serum monomethyl-L-arginine level and a higher L-arginine/ monomethyl-L-arginine ratio. Importantly, significantly decreased serum IL-6, and adhesion mol-ecule levels were observed in transgenic mice in comparison to control after LPS treatment. Fur-thermore, reduced endothelial permeability in the LPS-treated transgenic mice was noted as com-pared to LPS-treated control. The human enzymes (hHO-1, hE5NT, hENTPD1) simultaneously encoded in transgenic mice demonstrated benefits in sev-eral biochemical and functional aspects of endothelium. This is consistent in use of this approach in the context of xenotransplantation.

Cancer is a complex disease, considered a major public health problem worldwide. Among the types of cancer, melanoma, and leukemias present high mortality rates in Brazil and worldwide. Currently, conventional cytotoxic treatments cause severe side effects by the non-selectivity between normal cells and cancer cells. Therefore, molecules of natural origin with more efficient anticancer properties and that present fewer adverse effects are of extreme importance for cancer therapy and improvement in patients’ quality of life. This study isolated, identified, and characterized the chemical structure of a new anthraquinone present in the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by NMR. Subsequently, their cytotoxic activity was evaluated by the MTT method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. By flow cytometry technique, the apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2'-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2'-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and CA+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed-cell death pathways induced by 2'-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2'-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

Foxtail millet (Setaria italica (L.) P. Beauv) is an important food and forage crop that is well adapted to nutrient-poor soils. However, little is known about how foxtail millet adapts to low nitrogen (LN) at the physiological and molecular levels. In the present study, two foxtail millet varieties with contrasting low nitrogen (LN) tolerance properties were investigated through integrative analyses of physiological featureparameters and transcriptomics. The physiological results showed that JG20 (high tolerance to LN) had higher biomass accumulation, nitrogen content and nitrogen use efficiency compared with JG22 (low tolerancesensitive to LN) under LN. JG20 had higher soluble sugar and soluble protein concentration in shoots compared with JG22 under LN, while contcentrations of soluble sugar and soluble protein contents were higher in the roots of JG22. Higher levels of CTK contentzeatin concentration were found in the shoots of JG20 com-pared with JG22, and a higher ABA contcentration was found in both the shoots and roots of JG22 compared with JG20 under LN. In the transcriptomics results, JG20 had more differentially ex-pressed genes (DEGs) than JG22 both in shoots and roots in response to LN. These LN-responsive genes were enriched in glycolysis, starch and sucrose metabolism, photosynthesis, biosynthesis of amino acids, hormone metabolism and nitrogen metabolism. Furthermore, the high-affinity nitrate transporter gene, SiNRT2.1, and glutamine synthetase gene, SiGS5, chlorophyll apoprotein of photosystem II gene, SiPsbQ, ATP synthase subunit gene, b, auxin-responsive protein gene, SiIAA25, and aldose 1-epimerase gene, SiAEP, in shoots, and high-affinity nitrate transporter gene, SiNRT2.3, SiNRT2.4, and glutamate synthase gene, SiGOGAT2, auxin-responsive protein gene, SiIAA4, fructose-bisphosphate aldolase gene, SiAEP5, in root, were important genes in-volved in the LN tolerance of foxtail millet. These results provide a detailed description of the physiological and transcriptome response of foxtail millet under LN condition.

Here we present an overview of speleothem δ18O records from South America, which mostly are available in the Speleothem Isotopes Synthesis and Analysis (SISAL_v1) database. South American tropical and subtropical δ18O time series are primarily interpreted as being driven by the amount effect and, consequently show the past history of the convection intensity of convergence zones such as the Intertropical Convergence Zone and the South America Monsoon System. We investigate past hydroclimate scenarios in South America related to the South American Monsoon System in three different time scales: Late Pleistocene, Holocene and the last two millennia. The precession driven insolation is the main driver of convective variability over the continent during the last 250 kyrs, including the Holocene period. However a dipole is observed between the west and east portions of the continent. Records located in the central region of Brazil appear to be weakly affected by insolation driven variability and more susceptible to the South Atlantic Convergence Zone. Cold episodic events in Northern Hemisphere increase the activity of the South American Monsoon System on all time scales, in turn increasing rainfall amounts in South America, as was documented during Heinrich events in the late Pleistocene and Bond events in the Holocene, as well as during the Little Ice Age.

Structurally related 7-acetyl-2-aryl-5-bromoindoles 2a–d and the 7-acetamido-2-aryl-5-bromoindoles 4a–d as well as their corresponding 3-trifluoroacetyl–substituted derivatives 5a–d and 5e–h were evaluated for potential antigrowth effect in vitro against the human lung cancer (A549) and cervical cancer (HeLa) cells. All of the 3-trifluoroacetyl–substituted 7-acetamido-2-aryl-5-bromoindoles 5e–h were found to be more active against both cell lines when compared to the chemotherapeutic drug, Melphalan. The most active compound 5g induced apoptosis in a caspase dependent manner for both cell lines. Compounds 5e–h were found to significantly inhibit tubulin polymerization. Molecular docking of 5g into the colchicine-binding site suggests that the compounds bind to tubulin by different type of interactions including pi-alkyl, amide-pi stacked and alkyl interactions as well as hydrogen bonding with the protein residues to elicit anticancer activity.

We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. Thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression.

Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.

Borneol and menthol were two terpenes wildly used as penetrate enhancer in transdermal drug delivery. To explore their penetration enhancement effect towards hydrophilic drug, 5-FU was selected as model drug. A method combined vitro permeation studies and coarse grain molecular dynamics was used to investigate their penetration enhancement effect towards 5-FU. As a result, although both borneol and menthol showed a penetration enhancement effect towards 5-FU, they differed a lot in the penetration enhancement mechanism, which was also thought to account for their different penetration enhancement effect. As for menthol, SC bilayer disrupting effect seemed to be its main mechanism. While for borneol, its mechanism seemed to be more complicated. Except for disrupting the SC bilayer, it could also increase the permeation of 5-FU by enhancing the diffusion rate of 5-FU or inducing the formation of transient pore. All of this enable us a molecular understanding of borneol and menthol’s penetration enhancement effect towards hydrophilic drug, which might provide some guidance in the latter research and application.

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

Porous β-tricalcium phosphate (Ca3(PO4)2; β-TCP) was prepared by freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing β-TCP slurries above a liquid nitrogen surface at −180 °C with subsequent immersion in liquid nitrogen at −196 °C. These materials were then dried under reduced pressure in a freeze-dryer after which they were sintered by heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the β-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of up to 1.24 µm and macroscopic, interconnected pores up to 25.8 µm in size. The effects of non-ionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (75%) and good compressive strength (&gt;2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

Background: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of the study is to evaluate the clinical findings of glucose 6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiency, to prevent further examinations for prolonged jaundice, and to contribute by regulating its treatment. At the same time, it is to determine whether systemic-immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can be used in addition to conventional complete blood count (CBC) parameters in the diagnosis of neonatal prolonged jaundice. Methods: In full term neonates with hyperbilirubinemia who were admitted to Medicine Hospital between January 2019 and January 2024 with the complaint of jaundice, 167 infants with a serum bilirubin level above 5 mg/dL, whose jaundice persisted after the 10th day, were included in the study. Results: 63.5% of the patients were male and the mean age was 31±6 days. G6PD was negatively perfectly correlated with NLR (r: -1; p

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

Placental growth factor (PlGF or PGF) is a member of the VEGF family, which is known to play a critical role in pathological angiogenesis, inflammation, and endothelial cell barrier function. However, the molecular mechanisms by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remain elusive. In this study, we performed transcriptome-wide profiling of differential gene expression for human retinal endothelial cells (HRECs) treated with PlGF antibody. The effect of antibody treatment on the samples was validated using trans-endothelial electric resistance (TEER), and western blot. A total of 3760 genes (1750 upregulated and 2010 downregulated) were found to be differentially expressed between the control and PlGF antibody treatment group. These differentially expressed genes (DEGs) were used for gene ontology and enrichment analysis to identify gene function, signal pathway, and interaction networks. The gene ontology results revealed that catalytic activity (GO:0003824) of molecular function, cell (GO:0005623) of the cellular component, and cellular process (GO:0009987) were among the most enriched biological processes. Pathways such as TGF-β, VEGF-VEGFR2, p53, apoptosis, pentose phosphate pathway, and ubiquitin-proteasome pathway, were among the most enriched, and TGF-β1 was identified as a primary upstream regulator. These data provide new insights into the underlying molecular mechanisms of PlGF in mediating biological functions, in relation to DR.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

children is challenging. An important advance is the 15-questions Pictorial Personality Traits Questionnaire for Children. A study on students from 10 to 13 years old in Poland validated the questionnaire but with some observations. Thus, there is a need for replication and stronger evi-dence in this age group. In Chile, we replicated the study with 3,423 4th-graders (9 to 12 years old). Teachers, in regular sessions, applied the questionnaire to their entire classes. We found similar results, including that asexual pictograms worked well in both genders. We also found positive relationships between conscientiousness, openness, and extraversion with mathematical performance. Furthermore, a combination of these three traits has a relationship with math performance twice as big as each trait alone. Moreover, students with the lowest scores in this combination of personality traits (6.6% of students) have 0.27 standard deviations less in mathematical performance than those with the highest score, which is 74.3% of students. To the best of our knowledge, this is the first time that a study finds a strong relationship between a combination of personality traits gathered with a 15-question questionnaire and fourth-graders´ math perfor-mances.

Stress is one of the important factors affecting the growth and development of plants. In recent years, a large body of data on transcriptional changes in response to stress in plants has been obtained. Despite the fact that the important role of the regulation of translation in response to stress has been proven in plants, knowledge in this area remains extremely scarce. In this review, we focused on mRNA translation in the cytoplasm of higher plants. Most of the current research on the effects of translation has been done in yeast and mammalian systems. Translation factors and mechanisms are mostly conserved among eukaryotes; however, some differences are known to exist among plants. A comprehensive understanding of the complex apparatus of translation and its regulation in plants is required. In this work, we have tried to update modern ideas about the regulation of translation under conditions of abiotic stress.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "Classic" BPD, as per the original description, is less common now. "New BPD," which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving due to medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of serotonin (5-HT) neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to PS. PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5-HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine–tryptophan–ketoglutarate (HTK) solution is a preservative used during organ transplantation. Can HTK also protect neurons from severe hypoxia (SH) following CA? We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and NADPH oxidase-4 (NOX4) expression were evaluated at different time points till 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluating NOX4 and H2O2 level in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persisted HIF-1α expression, reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK’s effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity and NOX4 gene expression were all decreased in the brain specimen of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution.

Relationship between the results of penile duplex doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data of 148 patients with ED were analysed retrospectively. Patients who did not respond to therapy were classified as Group I (n = 32), those responded partially were classified as Group II (n = 40) and complete responders were classified as Group III (n = 76). Age, comorbid diseases, vascular and penile pathology were compared among the three groups. While diabetes mellitus (DM) and dyslipedimia positivity adversely affect the response to treatment, the presence of hypertension (HT), peyronie's disease and priapism increase the therapeutic response to the treatment (p < 0.05). Arterial insufficiency was present in 20(30.3%), 25(37,9%) and 21(31.8%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Venous insufficiency was observed in 3(14.3%) patients in Group I and in 8(85.7%) patients in Group III (p = 0.001). Arterial/venous insufficiency was seen in 9(30%), 14(46.7%) and 7(23.3%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Response rate to treatment was highest in normal patients according to PDDU, followed by patients with venous insuffiency. Besides, it was found that DM decreased the response to treatment, whereas response was increased in cases with HT, priapism and Peyronie’s disease.

Polymorphism of vitamin D3 receptor (VDR), has been associated with low bone mineral density and other immune and metabolic disorders; however, its impact on mortality of female dialysis patients is not well studied. This study aimed to identify bone mass-related factors, VDR gene polymorphism, and their interaction with morbid conditions that could influence all-cause mortality. In 246 female dialysis patients, age 43±11 years on continuous ambulatory dialysis peritoneal; 48%, haemodialysis; 23% and automated peritoneal dialysis; 29%. Tscore, Ca, PO4, albumin, hs-CRP, osteoprotegerin, fetuin, osteocalcin, iPTH, PINP and β-CTx were measured. PCR products were digested with Bsml to analyze VDR polymorphisms. Patients n=229; were followed for a median of 17 (15-31) months; 42 patients died. Bsml polymorphism, bb=64% and BB+Bb=36%. Hs-CRP was the risk of death in multivariate Cox Analysis. Patients with bb and inflammation had a higher risk of death (HR 2.48, 95% CI 1.08-5.68) persisted after adjustment for age, diabetes and iPTH (HR 2.33; 95% CI, 1.01-8.33) and after further adjustment for vintage, albumin, osteoprotegerin and vitamin D therapy (HR 3.49; 95% CI, 1.20-10.9). We may conclude that the presences of the bb genotype of VDR and inflammation have additive effects on all cause-mortality in females in CAPD, APD, and HD patients.

To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon shaped molecule. We analyse the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme 1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH), and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.

In recent times, models like the Transformer have showcased remarkable prowess in tasks related to natural language processing. However, these models tend to be excessively intricate and demand extensive training. Additionally, while the multi-head self-attention mechanism in the Transformer model aims to capture semantic connections between words in a sequence, it encounters limitations when handling short sequences, thereby limiting its effectiveness in 5-polarity Arabic sentiment analysis tasks. The switch-transformer model has recently emerged as a high-performing alternative. Nevertheless, when these models are trained using single-task learning, they often fall short of achieving exceptional performance and struggle to generate robust latent feature representations, especially when working with compact datasets. This challenge is particularly pronounced in the case of the Arabic dialect, which is considered a low-resource language. Given these constraints, this research introduces a novel approach to sentiment analysis in Arabic text. This method leverages multitask learning in tandem with the switch-transformer shared encoder to enhance model adaptability and refine sentence representation. By introducing a mixture of expert (MoE) mechanism that break down the problem into smaller, more manageable sub-problems, the model becomes adept at handling lengthy sequences and intricate input-output relationships, benefiting both five-point and three-polarity Arabic sentiment analysis tasks. This proposed model effectively discerns sentiment in Arabic dialect sentences. The empirical results highlight the outstanding performance of the suggested model, as evidenced in evaluations on the Hotel Arabic-Reviews Dataset, the Book Reviews Arabic Dataset, and the LARB dataset.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA. However, several are under development, and the FDA anticipates their fast entry, as evidenced by the FDA's actions of issuing GE-specific guidelines. The potential of GE in treating diseases far supersedes any other modality due to the recognized role of genes in most human diseases. While GT products add missing genes, GE tools can overcome many aberrations. However, GE presents many safety challenges, including off-target impact, delivery consistency, and long-term effects of gene-fixing. However, most of these concerns will be resolved once the FDA begins approving them, leading to hundreds of products capable of treating untreatable diseases.

A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPP’s) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c] pyridine (13g), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead. Certain structure-activity relationships were established in the course of this study which were rationalized by the induced-fit docking experiments in silico.

Cancer patients may experience significant distress. The “Emotion Thermometers” (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an NGO, and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of Distress and 33 items of the problem list. Four items - sadness, depression, sleep and breathing - were found to be significantly related to a higher level of Distress. Additionally, women and those who were in the palliative phase also had significantly higher levels of Distress. Conclusions: The results confirm the need for early emotional screening in cancer patients, as well as the relevance of attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psy-chosocial services.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

Recent advancements in surgical and anti-cancer therapies have provided significant hope of long survival in patients with pancreatic cancer (PC). To realize this hope, routine medical checkups of asymptomatic people should be performed to identify operable PCs. In this study, we evaluated the efficacy of medical checkups using abdominal ultrasonography (US). We retrospectively analyzed 374 patients with PC at our institute between 2010 and 2021. We divided these patients into several groups according to the diagnostic approach and compared their background and prognosis. These groups comprised PCs diagnosed through (a) symptoms, 242 cases; (b) US during medical checkup for asymptomatic individuals, 17; and other means. Of the 375 patients, 192 were men (51.3%), and the median age was 74 years (34–105). Tumors were located in the pancreatic tail in 67 patients (17.9%). Excision ratio and 5-year survival rate were significantly better in group (b) than in (a) (58.8% vs. 23.1%, P<0.01 and 42.2% vs. 9.4%, P<0.001, respectively). The prognosis of patients diagnosed using US during medical checkup was better than that of patients identified through symptomatic presentation of PC. US for asymptomatic individuals with PC might be useful for promoting better prognosis of PCs.

Phytonutrients are plant foods that contain many natural bioactive compounds, called phytochemicals, which expose specific biological activities. These phytonutrients and their phytochemicals may play an important role in health care maintaining normal organism functions (as preventives) and fighting against diseases (as therapeutics). Phytonutrient’s components are the primary metabolites (i.e., proteins, carbohydrates, and lipids) and phytochemicals or secondary metabolites (i.e., phenolics, alkaloids, organosulfides, and terpenes). For years, several phytonutrients and their phytochemicals have demonstrated specific pharmacological and therapeutic effects in human health such as anticancer, antioxidant, antiviral, anti-inflammatory, antibacterial, antifungal, and immune response. This review summarizes the effects of the most studied or the most popular phytonutrients (i.e., turmeric, garlic, cinnamon, graviola, and oregano), and any contraindication found. This article also calculated the physicochemical properties of the main phytochemicals in the selected phytonutrients using Lipinski’s, Veber’s and Ghose’s rules. Based on our revisions for this article, all these phytonutrients have consistently shown several in vitro, in vivo, and clinical studies with great potential as preventives and therapeutics on many diseases.

We live in the time of profound transformations commonly labelled with the word “globalization”. The rise of one ecological-technological-social system encompassing our whole planet is an important element of these processes. Solving big global problems demands knowledge of two complementary sorts: on the one hand – going “in depth”, on the other – going “in breadth”. The present paper assumes the second (in a sense: philosophical) perspective. It tries to analyze some relations between the development of technology (IT) and the development of democracy. The notion of democracy, its various forms and axiological reasons for it are considered first. In the subsequent chapter different consequences (both positive and negative) the IT development has for contemporary democracy are discussed. In the next chapter the evolutionary nature of the technological development is debated as well as the question of (democratic) control of this process. The development of Artificial General Intelligence is presented as a challenge for democracy

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C₁₆-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition. The emergence of novel stationary phases added to the need for a less complex mobile phase has led to the development of a new HPLC assay called alphaLogD, applicable to neutral and basic compounds at pH 7.4, that combines superficially porous particles, a high number of equilibriums between solutes and stationary phase, and results in a lower number of isocratic methods to determine the logk’_w at a higher throughput. Statistical studies have been run to successfully evaluate the alphaLogD method compared to the Shake-Flask method and to allow this lipophilicity measurement into the so-called Beyond-Rule-of-5-molecules space.

2,5-Di(hydroxymethyl)furan (DHMF) is a high-value chemical block than can be synthesized from 5-hydroxymethylfurfural (HMF), a platform chemical that results from the dehydration of biomass-derived carbohydrates. In this work, the HMF biotransformation capability of different Fusarium species was evaluated and F. striatum was selected to produce DHMF. The effects of the inoculum size, glucose concentration and pH of the media over DHMF production were evalu-ated by a 23 factorial design. A substrate feeding approach was found suitable to overcome the toxicity effect of HMF towards the cells when added at high concentrations (>75 mM). The pro-cess was successfully scaled-up at bioreactor scale (1.3 L) with excellent DHMF production yields (95%) and selectivities (98%). DHMF was purified from the reaction media with high recovery and purity by organic solvent extraction with ethyl acetate.

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Besides, from pharmacogenomic research it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1 and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarkers microRNA could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

In recent years, remote sensing technology has been widely used to predict forest stand parameters. In order to compare the effects of different features of remote sensing images and topographic information on the prediction of forest stand parameters, multivariate stepwise regression analysis method was used to build estimation models for important forest stand parameters by using textural and spectral features as well as topographic information of SPOT-5 satellite images in northeastern Heilongjiang Province in China as independent variables. The study results show that the optimal window to predict forest stand parameters using textural features of SPOT-5 satellite image is 9×9; the ability of textural features was better than that of spectral features in terms of predicting forest stand parameters; with the inclusion of topographic information, the accuracy of prediction of all models was improved, of which elevation has the most significant effect. The highest accuracy was achieved when predicting the stand volume (SV) (R²_adj=0.820), followed by basal area (BA) (R²_adj =0.778), accuracy of both above models exceeded 75%. The results show that models combined use of textural, spectral features and topographic information of SPOT-5 images have a good application prospect in predicting forest stand parameters.

The microbiome is capable of modulating the bioavailability of chemotherapy drugs mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic properties on cancer cells. In this study we addressed the question whether the cytostatic bacterial metabolites (cadaverine, indolepropionic acid, indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil, paclitaxel). The chemotherapy drugs were applied in a wide concentration range to which a bacterial metabolite was added in a concentration within its serum reference range and the effects on cell proliferation were assessed. There was no interference between doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib and the bacterial metabolites. Nevertheless, cadaverine increased the Hill coefficient of the inhibitory curve of 5-fluorouracil and indolepropionic acid increased the IC50 value of 5-fluorouracil that are either disadvantageous effects or effects of unknown significance. Nevertheless, indolepropionic acid decreased the IC50 value of paclitaxel that is a potentially advantageous combination.

This paper outlines the evolution of a learning technology interface from a Beta version to launch with educators and its alignment to pedagogical theory, designed to maximise collaboration between teacher and student. It explores how the “co-creation” of curricula via textual sources that underpin teaching and learning can be enhanced through interactive e-books and outlines the challenges involved in this praxis. With a number of stakeholders involved in the live use of the platform (including teachers, students, HE educators, course instructors, curriculum designers and software developers), iterative feedback loops informed real-time design improvements to both the interface and the-ory. This collaboration utilised a design-based research (DBR) approach (Wang and Hannafin, 2005), which is outlined here as explanation of how the tool developed and how iterative feedback helped to reconsider the challenges educators face in implementing pedagogical innovation across differing contexts. We propose how speculative design (Lukens and DiSalvo, 2012) and Activity Theory (Engeström, 1987) workshops can methodologically enhance the planning and evaluation phases inherent to DBR approaches, which involve students to prepare for educators’ innovation. Finally, we conclude with how educators can utilise these design principles using stratified approaches to help prepare organisational approaches for innovation.