We have synthesized and examined a series of calix[4]arene-based chemosensors containing thiosemicarbazone or thiourea as a binding site and a pyridine-chromophore unit in various conformations. These conformations include pinched cone (I), cone (III and IV), and 1,3-alternate (II and V). Our objective was to assess the binding abilities of these sensors towards anions and cations using different spectroscopic techniques. All receptors demonstrate the ability to recognize cations, with notable distinctions between them. Receptor I demonstrates a broad spectrum of ion recognition, encompassing Ag+, Cu2+, Co2+, Ni2+, and Zn2+. Receptors IV and V also exhibit complex formation with Co2+, Ni2+, and Cu2+ ions. Sensors II and III demonstrate exceptional selectivity for recognizing the copper (II) ion. When studying anions, only receptor I yielded satisfactory results. This is due to the thiosemicarbazone bridge and its spatial orientation in the pinched cone conformation, which allows for an interaction to occur. It is worth noting that sensors IV and V, which are fluorescent molecules due to the triazolo pyridine unit in their structure, exhibit particularly noteworthy behavior. The highest association constant is observed for cobalt (II) complexes, with values of 6.59 and 2.38 (x1012 mol/L)-2 for receptors IV and V, respectively. Our findings indicate that there are no significant differences in selectivity and sensitivity between ca-lix[4]arene receptors in 1,3-alternate and cone conformations.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

This study introduces a novel, robust, and efficient method for the simultaneous quantitative determination of three sunscreen filters namely 4-methylbenzylidene camphor, octyl methoxycinnamate, and avobenzone, in a moisturizing sunscreen cream specifically designed for acne-prone skin. The method employs high performance liquid chromatography with photodiode-array detection, providing reliable separation of the analytes. Chromatographic separation was achieved using a Fortis Phenyl analytical column (150.0 x 2.1 mm, 5 μm), with isocratic elution at a flow rate of 0.4 mL/min. The mobile phase was composed of a 57/43 (v/v) mixture of acetonitrile/45 mM aqueous ammonium formate solution, ensuring sufficient resolution and peak symmetry for the target compounds. The method was validated comprehensively for critical performance parameters, including linearity, precision, accuracy, and robustness. Linearity was established across a suitable range for all three analytes, with high correlation coefficients. Precision was confirmed with intra-run and total precision coefficients of variation of ≤ 4.6 %, while accuracy assessments yielded a percent recovery between 98.6 and 100.4, for all quality control levels. Additionally, the method was able to effectively separate the sunscreen filters from other cosmetic ingredients, such as [β-(1.3), (1.6)-D-glucan], Low Molecular Weight (LMW) hyaluronic acid and plant extracts ensuring specificity in complex formulations. This straightforward and time efficient sample preparation process, involving methanol extraction followed by serial dilution, makes the method suitable for routine quality control in cosmetic laboratories. The method was successfully applied to the analysis of two different lots of a commercial sunscreen cream, achieving excellent recovery for all filters, ranging between 94.6% and 99.8%, thus demonstrating its reliability and applicability for the quality control of cosmetics.

The paper proposes a universal algorithm for parallelizing calculations that arise when using highly-optimized minimization functions available in many computing packages. The main idea of the proposed algorithm is based on the fact that although the “inner workings” of the minimization function used may not be known to the user, it inevitably uses in its work auxiliary functions that implement the calculation of the minimized functional and its gradient, which are usually implemented by the user, which means that in most cases they can be parallelized relatively easily. The paper discusses in detail both the parallelization algorithm and its software implementation using MPI parallel programming technology. Examples of the software implementation of the proposed algorithm are demonstrated using the Python programming language, but can be easily rewritten using the C/C++/Fortran programming languages.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

Background: In 2023, ChatGPT-4 has been impactful across several sectors including healthcare, where it aids in medical information analysis and education. Electronic Patient-Reported Outcomes (ePROs) play a crucial role in monitoring cancer patients’ post-treatment symptoms, enabling early in-terventions. However, managing the voluminous ePRO data presents significant challenges. This study assesses the feasibility of utilizing ChatGPT-4 for analyzing side effect data from ePROs. Methods: Thirty cancer patients were consecutively collected via a web-based ePRO platform, reporting side effects over 4 weeks. ChatGPT-4, simulating oncologists, dietitians, and nurses, analyzed this data and offered improvement suggestions, which were then reviewed by professionals in those fields. Results: Two oncologists, two dieticians and two nurses evaluated the AI’s performance across roles with 540 reviews. ChatGPT-4 excelled in data accuracy and completeness, and was noted for its empathy and support, enhancing communication and reducing caregiver stress. It was particularly effective as a dietician. Discussion: ChatGPT-4 shows promise in processing ePRO data with high accuracy, suggesting that AI can enhance clinical decision-making. Nevertheless, its limitations in emotional engagement highlight the need for AI to supplement, not replace, human care. Emphasizing the role of dietitians underscores the importance of nutritional advice in cancer care. Future studies will further explore the feasible application of AI and ePRO in cancer care clinical processes.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.

Metabolomics profiling for accurate and reliable quantification of organic acids that carry a carboxylic acid functional group in complex biological samples, remains a major analytical challenge in clinical chemistry research. Several procedural barriers associated with quantification of clinically important carboxylic containing metabolites (CCMs) including spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column, limit the sensitivity, specificity, and reproducibility of multiple-reaction monitoring (MRM) based LC-MS assay development. We report a targeted metabolomics-based analytical method for the quantification of CCMs using phenylenediamine derivatization. Accurate and sensitive quantification of CCMs is successfully demonstrated in an array of biological matrices. Recovery of metabolites from different matrices (plasma, serum, urine, saliva, tissues, and cell extracts), ranged from 90% to 105%, with all the CVs ≤ 10%. The method showed linearity over a broad dynamic range from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 for most of the metabolites tested herein, that covers broad-based applicability with the analysis of biological samples. In most cases the LODs were as low as 0.01 ng/mL. The phenylenediamine-based derivatization of carboxyl acid library consisting of more than 70 endogenous metabolites was constructed for metabolite identification, which spanned more than 40 biological pathways. The library included a wide-variety of structurally variant CCMs such as amino acids/conjugates, short to medium chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids and some ring-containing CCMs. We compared the CCMs profiles of pancreatic cancer cells with normal pancreatic epithelial cells to test and validate the biological utility of this method. The comparative profiling between cancerous and normal cells resulted in the identification of potential biomarkers in pancreatic cancer, and their correlation with several key metabolic pathways such as central carbon energy metabolism, protein metabolism, including TCA cycle, glycolysis, Gln-Glu pathway, and biosynthesis of amino acids and unsaturated fatty acids was established. The method, described herein, for the first time enables the sensitive and highly specific quantification of CCMs on small sample size with high reproducibility in a high throughput manner. Given the biological and functional significance of this class of metabolites, this mass spectrometry based targeted quantitative assay, fills an important gap and is likely to support a wide range of applications for basic, clinical, and translational research.

This study proposes an innovative pharmacovigilance approach, VIGI-4, leveraging ChatGPT Teams Pro version. Our method involves aggregating data from all phase 4 studies published in February 2024 to identify adverse reactions. These results are categorized by disease state alphabetically, demonstrating the method's capacity to generate structured and easily navigable outputs. The results section is tailored to exemplify the valuable, actionable insights attainable through our workflow. This research emphasizes the game-changing potential of integrating advanced technologies such as ChatGPT into pharmacovigilance, signaling a new era in safeguarding drug safety.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unal-tered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex ter-minates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant con-tributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

The relationship between nations is largely seen as a peripheral issue in the recent history of political philosophy and in the majority of discussions of political philosophy issues today. The idea of a universal natural state were countries are seen as essentially self-sufficient, functional units, and have been proposed to represent the relative lack of moral standards guiding relationships between nations. At one extreme of the tradition, international thought has substituted raison d'état being the highest norm for any universal laws governing relations between states, a view embodied by Machiavelli, Rodin, and others and Hobbes , The lack of supranational political powers has led to the conclusion that, even in cases where the possibility of international moral relationships has been acknowledged, such as in post-Grotian publications on international law, these ties are significantly weaker than in-tranational social bonds. The justification and aversion to war—the primary mode of social in-teraction in the natural condition of the world—is the only issue in the field of global relations to have received substantial theoretical study. Even though this disregard was justified in the past, a number of recent events force us to re-consider the "recalcitrance of international affairs to being theorized about."2. The growing gap between both prosperous and impoverished nations; the emergence of centers of economic in-fluence beyond the reach of effective state regulation; the emergence of severe food and energy shortages brought on, at least in part, by national governments' pursuit of disorganized and uncontrolled growth policies; the growing sensitivity of domestic Countries to the outside eco-nomic, political, and cultural events are some of these developments , requests from third-world nations for greater equal access to international politics and economy. To put it in terms more familiar to conversations about this topic, the rise of "low politics" in negotiation and "welfare questions" within global forums corresponds with the growing influence of transnational con-nections and international agreements on human well-being. Not because "high politics"—that is, the threat and prevention of war—has lost significance; rather, it is just one issue among many for which international cooperation is now required in order to find answers.

Zinc Oxide nanoparticles functionalized with APTES were obtained to evaluate their CH4 and CO2 adsorption and separation behavior. First, ZnO nanoparticles were obtained by a precipitation method and subsequently coated with (3-aminopropyl)-triethoxysilane (APTES). The nanoparticles sample was characterized by UV-Vis, FT-IR spectroscopy, TGA, XRD, TEM/EDX, XPS and N2 adsorption at 77 K. CH4 and CO2 adsorption experiments were carried out at 298 K in a range between 0-10 bar. It was observed that the amount of gas adsorbed on the surface of the nanostructure is very small in comparison with other materials traditionally used for this purpose but slightly higher than those obtained in naked nanoparticles evaluated in previous studies.

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, H3K14ace, and H3K27ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p < 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

International law faces numerous challenges in the 21st century, ranging from the traditional issues of sovereignty to emerging threats like cyber warfare and climate change. This article explores the evolving landscape of international law, discussing both the challenges it faces and the prospects for its future. By examining the role of international organizations, the impact of technological advancements, and the growing influence of non-state actors, this article provides a comprehensive overview of the current state of international law and offers insights into how it can adapt to meet the demands of an increasingly interconnected world.

Businesses now formally enter the phase of "think power differentiation and gap" in response to the new economic climate. While AI, big data, empowerment via the internet, and other aspects of the digital economy help to improve technical capabilities and save operating costs, they also push businesses to innovate their strategies at a faster rate. Enterprises are strategically choosing to de-enterprise, moving from focusing on a single business functioning benefit to building an ecosystem of platform services that will give them a competitive edge. Additionally, the organization's structure is evolving continually from a vertical model to a curved working style, in order to achieve this, businesses must recognize the importance of data analysis in day-to-day management and operations, encourage the development of an organizational atmosphere that is driven by data, fully utilize digital technology, modularize areas or production links that perform related tasks, and encourage the reform of organizational structures. By streamlining the output of the product or service to the external community while also enhancing the company's financial performance model, switching from process-to result-oriented evaluation, and putting in place a customized authority and accountability framework. Replace outcome-focused evaluation with process-focused evaluation, and create a customized incentive scheme that balances power, accountability, and rewards.

Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigation for new therapeutic approaches is necessary. Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 6.97 μg/mL and 4.89 μg/mL, respectively. IMBZC did not alter cell growth of normal cells HEK293. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyzes revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. In conclusion, the study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

In this research, the primary goal was to investigate the relationship between strategic planning and organizational performance in Iraq's manufacturing context. The study's primary data sources were 360 manager respondents. The structured questionnaire was used to collect primary data from manufacturing firms located throughout Iraq. To analyze the result, the researcher used descriptive statistics, correlation, and multiple regression analysis. SPSS version 16 software was used to conduct data analysis. The result reveals that the process of strategic planning has a beneficial effect on financial performance. Environmental scanning has a statistically significant positive effect on a company's non-financial performance. Management participation and planning formality positively and statistically significantly affect a business's non-financial performance at the 10 percent level. The domain of strategy and technique has not impacted the company's non-financial performance.

Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD) induced Ventricular arrhythmias, that exhibit heightened proinflammatory-like pathology which is also observed in human obesity VT, as well as immunofluorescence, and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling exhibit enhanced Ventricular arrhythmias /SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat (LFD) diet fed controls, HFD promotes phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4) leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 more than LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval that resulted in greater susceptibility to VT/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective VT therapy in the vulnerable obese patient population.

Background and Objectives: To assess femoral shaft bowing (FSB) in the coronal and sagittal planes and introduce the clinical implications of total knee arthroplasty (TKA) by analyzing a three-dimensional (3D) model with virtual implantation of the femoral component. Materials and Methods: Sixty-eight patients (average age: 69.1 years) underwent 3D model reconstruction, incorporating medullary canals, by importing computed tomography (CT) data into Mimics® software. A mechanical axis (MA) line was drawn from the midportion of the femoral head to the center of the intercondylar notch; proximal/distal straight centerlines (length, 60 mm; diameter, 1 mm) were placed in the center of the medulla canal. Acute angles between the two centerlines were measured as lateral and anterior bowing. The acute angle by distal centerline and MA line was measured as distal coronal and sagittal alignment in both anteroposterior (AP) and lateral views. The diameter of curve (DOC) of the medulla along the posterior border was measured. Results: The mean lateral bowing on the AP view was 3.71°, and the mean anterior bowing on the lateral view was 11.82°. The average DOC of the medullary canal was 1501.68 mm. The distal coronal alignment of all femurs was an average of 6.40°, and the distal sagittal alignment was 2.66°. Overall, 22 femurs had coronal bowing, 42 had sagittal bowing, and 15 had both. Conclusion: In Asians, FSB is present in coronal, sagittal, or both directions. Increased anterolateral FSB may lead to cortical abutment in the sagittal plane despite limited space in the coronal plane. During TKA, distal coronal alignment can guide distal femoral valgus cut angle, whereas distal sagittal alignment helps anticipate femoral component positioning, avoiding anterior notching. Osteotomy along the anterior cortical bone to prevent notching may result in outliers due to differences between distal sagittal alignment and distal anterior cortical axis.

The current emphasis in the advancement of space-based synthetic aperture radar (SAR) is on lightweight payloads under 100kg with resolutions surpassing 1m. This focus is directed towards meeting the launch criteria for multiple satellites on a single rocket and cutting costs. This article discusses the creation and progress of a Ku-band SAR payload for the Taijing-4(03) Satellite, launched on January 23, 2024 accompanied by four other satellites. The SAR payload design was customized to meet the demands of a micro-nano satellite platform, resulting in a lightweight, flat design weighing less than 80kg, seamlessly integrated with the plate-shaped satellite platform. The article also introduces a beam optimization strategy for the phased array SAR antenna, significantly boosting the SAR system’s performance. The SAR payload provides various operating modes like slide-spot, strip, scan 1, scan 2, and others, with a maximum achievable resolution exceeding 1m. Extensive in-orbit testing of the payload produced numerous high-quality SAR images with potential uses in emergency disaster mitigation, safeguarding ecosystems, monitoring forests, managing crops, tracking sea ice, and more.

The goal of the study is to assess the potential correlation between maternal Sars-cov-2 infection , detected three months before the second trimester anomaly scan, and fetal iperecogenicity in order to determine whether or not this could be considered a predictive factor for maternal-fetal complications . The study included 48 pregnant women who did not have any clear maternal or fetal problems. These individuals had an anomaly scan in the second trimester, as well as amniocentesis and fetal cariotyping, and then RT-PCR testing on their placental tissue after birth to rule out transplacental transmission. There have been no reports of fetal abnormalities via amniocentesis or fetal cariotyping. The patients experienced a high rate of spontaneous births (83%). Fetal development problems (2%) and premature delivery (4%) were uncommon, although placental swabs revealed a possibility of viral transmission across the placenta itself. To the best of our knowledge, this is the first observational study to show that detecting isolated intestinal hyperechogenicity during an abnormality scan in fetuses of women infected with Sars-Cov-2 in the previous three months does not appear to be a predictor of poor maternal-fetal outcomes, but may be linked to transplacental virus transmission.

With the aim to develop novel scaffolds for sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt) protected mercapto acids, followed by removal of the acid labile S-Mmt group. This method allowed the efficient synthesis of the title compounds in high yield and purity, which were further used in the development a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with preformed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nanosized characteristics of the initial liposomes and allowed sustained release of calcein (which was used as a chromophore), providing evidence for the efficient synthesis of a novel drug release scaffold consisted of nanoliposome building blocks.

This paper presents the PEnsemble 4 model, a sophisticated machine learning framework that integrates IoT-based environmental data to accurately forecast maize yield. With the projected significant growth in global maize demand over the next decade, the inherent risks posed by the crop’s dependence on weather conditions necessitate improved prediction capabilities. The PEnsemble 4 model, developed with high accuracy, incorporates comprehensive datasets encompassing soil attributes, nutrient composition, weather conditions, and UAV-captured vegetation imagery. By employing a combination of Huber and M estimates, the PEnsemble 4 model effectively analyzes temporal patterns in vegetation indices, specifically CIre and NDRE, which serve as reliable indicators of canopy density and plant height. In addition, this research significantly contributes to precision agriculture by offering an efficient and sustainable alternative to conventional farming practices through precise yield predictions. Notably, the PEnsemble 4 model enables earlier estimation, advancing the timeline for yield prediction from the conventional day 100 in the R6 stage to day 79 in the R2 stage. This improvement enhances decision-making processes in farming operations. The remarkable accuracy rate of 91% underscores the importance of adopting a multifaceted data approach that harnesses IoT-derived environmental insights. Additionally, the PEnsemble 4 model extends its benefits beyond yield prediction, facilitating the detection of water and crop stress, as well as disease monitoring in broader agricultural contexts. Ultimately, the PEnsemble 4 model establishes a new standard in maize yield prediction, revolutionizing crop management and protection through the synergistic utilization of IoT and machine learning technologies.

.Bacground: Sepsis remains a major health challenge worldwide, characterized by a dysre-gulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients. Method: This study retrospectively analyzed 309 sepsis patients admitted to the Internal Me-dicine and Anaesthesia ICUs between December 12, 2021, and December 15, 2023, to inves-tigate the relationship between FIB-4 levels, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) and clinical outcomes. Results: The study found that higher FIB-4 measurements were statistically significantly asso-ciated with increased 28-day mortality, with a cut-off value of 4.9 providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated Conclusion:FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.

The reactivity of 3,5-di-(pyridin-4-yl)-1,2,4-thiadiazole (L1) with 1,4-diiodotetrafluorobenzene (1,4-DITFB) was explored and the halogen-bonded 1:1 co-crystal (1) was successfully isolated and structurally characterized.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

The hydrophobic reagent 6-hexyl-4-(2-thiazolylazo)resorcinol (HTAR) was investigated as part of a cloud point extraction (CPE) system for the spectrophotometric determination of Zn(II). In the system, complexes with different stoichiometries, including 1:1 and 2:2 (Zn:HTAR), are formed. Their ground-state equilibrium geometries were optimized at the B3LYP/6-31G level of theory. The obtained structures were then used to calculate vertical excitation energies in order to generate theoretical UV/Vis absorption spectra. The comparison between theoretical and experimental spectra demonstrated that, under optimal conditions, a binuclear complex containing oxygen bridging atoms is the dominant species. The absorbance was found to be linearly dependent on the concentration of Zn(II) within the range of 15.7 to 209 ng mL–1 (R2 = 0.9996). The fraction extracted (%E), logarithm of the conditional extraction constant (log Kex), and molar absorption coefficient (ε) at λmax = 553 nm were calculated to be 98.3%, 15.9, and 4.47 105 L mol–1 cm–1, respectively. The method developed is characterized by simplicity, convenience, profitability, sensitivity, and ecological friendliness. It has been successfully applied to the analysis of pharmaceutical and industrial samples.

Autism has been described as a gastrointestinal and neurological condition that is represented by impairments in language and social situations. Recently reported increases in the occurrence of Autism Spectrum Disorder (ASD) have resulted in increased research into the environmental differences between areas with a high occurrence, as in the “Western” diet populations, and a more locally derived diet population, wherein the rate appears to be significantly less. Thirty autistic children (USA) ages 6 to 21, were sampled at three different intervals: prior to any intervention, post-xylitol intervention, and post-probiotic intervention. The sampling consisted of buccal swabs for MITOSWAB testing, and saliva for metatranscriptomics to determine the entire range of microorganisms and the metabolome. In addition, a “Blue Zone” subject component that included 30 Colombian children, ages 6-16, and who were healthy and within normal behavior standards, also had buccal swabbing and salivary sampling performed for comparison along with 30 healthy (no history medications, illnesses, or behavior issues) USA children matched for age and gender. Saliva samples were analyzed metatranscriptomically and artificial intelligence was utilized to discern important differences in the microbiome that included bacteria, archaea, fungi, and viruses, and microbial functions. Significant differences were noted, and seen in the temporal data, demonstrating shifts that may have been precipitated by the interventions, with both the probiotics and the polyols. Particular bacterial strains were significantly more prevalent in the autism subject group including a strain that reduces neurotransmitters by enzymatic degradation. This provided supporting evidence to the hypothesis that the occurrence of autism may also be influenced by low Gamma Amino Butyric Acid (GABA) levels during development. Also, of interest was the un-expected finding that verbal skills dramatically increased in 6 of the 30 ASD subjects following xylitol supplementation.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases including PD and type 2 diabetes mellitus (T2DM) suggesting a crucial interplay between the gut–brain axis. GLP-1R agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between February 2023 and February 2024. We used the terms “GLP-1”, “GLP-1 receptor”, “GLP-1R agonists”, “PD”, “T2DM”, “insulin”, “neurodegenerative disease”, “glucose”, “animal models”, “clinical trials” in different combinations. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies are also very promising enhancing the possibility of adding GLP1-R agonists in the current armamentarium of drugs available for PD treatment.

We synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids using an easy and short step synthetic route. All compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: GPR40, aldose reductase (AKR1B1), PPARγ and GLUT-4. Compound 1 displayed an EC₅₀ value of 0.075 μM against GPR40 and was an AKR1B1 inhibitor, showing IC₅₀ = 7.4 μM. Compounds 2 and 3 behave as AKR1B1 inhibitors, GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active compounds on these targets. Compounds 1-3 were tested in vivo at 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non insulin-dependent diabetes mellitus mice model. Compounds 2 and 3 showed robust in vitro and in vivo efficacy, and could be considered as promising multitarget antidiabetic drug candidates. This is the first report of a single molecule with these four polypharmacological target action.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

In vivo proton (1H) magnetic resonance spectroscopy (MRS) is a powerful noninvasive method which can measure Alzheimer’s disease (AD) related neuropathological alterations at the molecular level. AD biomarkers include amyloid-beta (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles. These biomarkers can be detected via postmortem analysis, but also in living individuals through positron emission tomography (PET) or biofluid biomarkers of Aβ and tau. This review offers an overview of biochemical abnormalities detected by 1H MRS within the biologically defined AD spectrum. It includes a summary of earlier studies that explored the association of 1H MRS metabolites with biofluid, PET, and postmortem AD biomarkers, and examined how apolipoprotein e4 allele carrier status influences brain biochemistry. Studying these associations is crucial for understanding how AD pathology affects brain homeostasis throughout the AD continuum and may eventually facilitate to develop potential novel therapeutic approaches.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

This study investigates the therapeutic potential of new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of depression in 48 male Wistar rats was used a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group receiving saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to intact animals. These results suggest that Compound I has a reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

Tuberculosis (TB) is a contagious disease, caused by Mycobacterium tuberculosis (MTB) that has infected and killed a lot of people in the past. At present treatments against TB are available at a very low cost. Since these chemical drugs have many adverse effects on health, more attention is now given on the plant-derived phytochemicals as potential agents to fight against TB. In this study, 5 phytochemicals, 4-hydroxybenzaldehyde, benzoic acid, bergapten, psoralen, and p-hydroxybenzoic acid, are selected to test their potentiality, safety, and efficacy against two potential targets, the MTB RNA polymerase and enoyl-acyl carrier protein (ACP) reductase, the InhA protein, using various tools of in silico biology. The molecular docking experiment, drug-likeness property test, ADME/T-test, P450 SOM prediction, pharmacophore mapping, and modeling, solubility testing, DFT calculations, and PASS prediction study had confirmed that all the molecules had the good potentiality to inhibit the two targets. However, two agents, 4-hydroxybenzaldehyde and bergapten were considered as the best agents among the five selected agents and they also showed far better results than the two currently used drugs, that function in these pathways, rifampicin (MTB RNA polymerase) and isoniazid (InhA protein). These two agents can be used effectively to treat tuberculosis.

Background/Objectives: Dengue is an arbovirus caused by a virus. It is an endemic infectious and occurs in warmer climates. It is not uncommon for the disease to be asymptomatic. However, the severe form can also be triggered and require intensive care. In this sense, patients present a wide variety of symptoms, which can trigger comorbidities such as arthritis, hematologic diseases, liver diseases, kidney diseases, autoimmune diseases, and, mainly, diabetes and hypertension. Among the symptoms, the presence of fever, myalgia, headache, nausea, vomiting, leukopenia, petechiae, retroorbital pain, arthralgia, rashes, skin eruptions, cardiovascular symptoms, respiratory symptoms and, depending on the severity, the presence of hemorrhages may occur. Methods: 235 patients' anonymized records from a secondary hospital were analyzed. Ethics approval was obtained and no patients’ consent was needed. Statistical analysis used frequency distributions and Chi-square tests, with SPSS software. Results: Similar to other studies, our results show that dengue can lead to complications. Furthermore, there was no significant difference in the distribution of the proportion of symptoms between patients with positive and negative serology. However, there was a significant association between age group and symptoms of fever and myalgia, with the occurrence of fever decreasing with increasing age and myalgia being more frequent in adults and less frequent in those <10 years old. Conclusions: Dengue can lead to complications, with fever becoming less common and muscle pain increasing as people age. Climate change could spread dengue to new areas. To address this, we need better vaccines and more effective mosquito control.

This paper describes the formulations for viscoplasticity of metals based on the Chaboche and Delobelle model. The implementations of the viscoplastic models were detailed herein and then implemented via user subroutines for material models (UMAT) in ABAQUS. Two typical metals, i.e., 316 Stainless Steel and Zircaloy-4, were chosen as examples and their viscoplastic behaviors were captured. Numerical simulations are compared to reported experiments to validate the models and the UMAT codes. Typical viscoplastic behaviors of both metals, such as stress relaxation and creep, were captured well against available experiments. We publicize all the data and codes via: https://github.com/XJTU-Zhou-group/ABAQUS_UMAT_316ss_Zr4.

K+ channels do play a role in cell shape changes observed during cell proliferation and apoptosis. Research suggested that the dynamics of aggregation of Aquaporin-4 (AQP4) into AQP4-OAPs isoforms can trigger cell shape changes in malignant glioma cells. Here, we investigated the relationship between AQP4 and some K+ channels in the malignant glioma U87 line. The U87 cells transfected with the human M1-AQP4 and M23-AQP4 isoforms were investigated for morphology, gene expression of KCNJ8, KCNJ11, ABCC8, ABCC9, KCNMA1, and Cyclin genes by RT-PCR, recording the whole-cell K+ ions currents by patch-clamp experiments. AQP4 aggregation into OAPs increases the plasma membrane functional expression of the Kir6.2 and SUR2 subunits of the KATP channels, and of the KCNMA1 of the BK channels in U87 cells leading to a large increase in inward and outward K+ ion currents. These changes were associated with changes in morphology with a decrease in cell volume in the U87 cells and an increase in the ER density. These U87 cells accumulate in the mitotic and G2 cell cycle. The KATP channel blocker zoledronic acid reduced cell proliferation in either M23 AQP4-OAPs and M1 AQP4-tetramers transfected cells leading to early and late apoptosis, respectively. BK channel sustains the efflux of K+ ions associated with the M23 AQP4-OAPs expression in the U87 cells, but it is downregulated in the M1 AQP4-tetramers cells; KATP channels are effective in the M1 AQP4-tetramers and M23 AQP4-OAPs cells. Zoledronic acid can be effective in targeting pathogenic M1 AQP4-tetramers cell phenotype inhibiting KATP channels and inducing early apoptosis.

Aquaporin-4 (AQP4) expression is associated with development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells were overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (600), with other genes such as Gpnmb, Itgax, Cd68 and Atp6v0d2 also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and absence of AQP4 prolonged its expression in this tissue.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity, and differentiate it from ICI-induced enterocolitis. Methods and Material: We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. Comparative analysis was performed to identify the key differences between the two groups. Results: Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-CD. On pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. Conclusion: ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and discontinuation of antineoplastic immunotherapy.

Introduction: A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). Material and Methods: The study analysed articles published in JCR journals from 2019 to 2024, including retrospective, prospective, case-control, or cross-sectional studies. It combined MESH and free terms for "Epileptogenesis" and "Neuroinflammation" and included searches for biomarkers previously reported in narrative reviews. Results: The study analysed 243 articles related to epileptogenesis and neuroinflammation, with 356 from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 52 evaluated by authors. 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. This systematic review provides acceptable support for five biomarkers: TNF-a and some of its soluble receptors (sTNFr2), HMGB1 and TLR-4, CCL2 and IL-33. Discussions: Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control levels of epileptic patients. Their value will be better defined by future studies.

High consequence pathogens such as Ebola, Marburg and Lassa viruses are handled in maximum containment Biosafety Level 4 (BSL-4) laboratories. Genetic material is often isolated from such viruses and subsequently removed from BSL-4 for a multitude of downstream analyses using readily accessible technologies and equipment available at lower biosafety level laboratories. However, it is essential to ensure that these materials are free of viable viruses before removal from BSL-4 to guarantee sample safety. This study details the in-house procedure used for validating the inactivation of Ebola, Marburg and Lassa virus cultures after incubation with AVL lysis buffer (Qiagen) and ethanol. This study’s findings showed no viable virus was detectable when high-titer cultures of Ebola, Marburg, and Lassa viruses were incubated with AVL lysis buffer for 10 minutes, followed by an equal volume of 95% ethanol for 3 minutes, using a method with a sensitivity of ≤0.8 log10 TCID50 as the limit of detection.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

The activity and cyclability of Cu-MOF-74 as catalyst was studied for the ligand-free C-O cross-coupling reaction of 4-nitrobenzaldehyde (NB) with phenol (Ph) to form 4-formyldiphenyl ether (FDE). Cu-MOF-74 is characterized by unsaturated copper sites in a highly porous metal-organic framework. The influence of solvent, reaction temperature, NB/Ph ratio, catalyst concentration and basic agent (type and concentration) were evaluated. High conversions were achieved at 120°C, 5 mol% of catalyst, NB/Ph ratio of 1:2, DMF as solvent and 1 equivalent of K2CO3 base. The activity of Cu-MOF-74 material was higher than other ligand-free copper catalytic systems tested in this study. This catalyst was easily separated and reused in five successive runs, achieving a remarkable performance without significant porous framework degradation. The leaching of copper species in the reaction medium was negligible. The O-arylation between NB and Ph took place only in the presence of Cu-MOF-74 material, being negligible without the solid catalyst.

Nobel metal nanohole arrays have been used extensively in chemical and biological systems due to their fascinating optical properties. Gold nanohole arrays (Au NHAs) were prepared as surface plasmon polaritons (SPP) generators for the surface-enhanced sum-frequency generation (SFG) detection of 4-Mercaptobenzonitrile (4-MBN). The angle-resolved reflectance spectra revealed that the Au NHAs have three angle-dependent SPP modes and two non-dispersive localized surface plasmon resonance (LSPR) modes under different structural orientation angles (sample surface orientation). An enhancement factor of ~30 was achieved when the SPP and LSPR modes of the Au NHAs were tuned to match the incident visible (VIS) and output SFG, respectively. This multi-mode matching strategy provided flexible controls and selective spectral windows for surface-enhanced measurements, and was especially useful in nonlinear spectroscopy where more than one light beam involved. The structural orientation- and power-dependent performance demonstrated the potential of plasmonic NHAs in SFG and other nonlinear sensing applications, and provided a promising surface molecular analysis development platform.

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC₅₀ values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).

We demonstrate, for the first time, a highly sensitive detection of 4-methylimidazole (4-MeI), a carcinogenic material, by applying an electric field enhancement technique using a terahertz (THz) metamaterial at the THz region. The THz metamaterials were fabricated with a metal array using an electric-field-coupled inductor-capacitor (ELC) resonator structure, and FDTD simulation showed good agreement with experimental results. We measured the THz spectra of the metamaterials to detect 4-MeI concentrations of 0, 1, 2, 5, 10, 15, and 20 mg/L. The resonance frequency of the metamaterial was shifted by approximately 8 GHz and transmittance at the resonance frequency increased to 2 x 10-3 as the concentration was increased, up to 20 mg/L. Our study provides new insight into application of metamaterials to detect carcinogen using a THz technique.

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

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Current neural network models can demonstrate reasonable-looking behavior, considered by some developers and researchers human-like. For example, a large language model GPT-3 is susceptible to human-like cognitive biases. Yet there is no data of such models solving emotional intelligence (EI) tasks. They are connected to the abilities that has been previously considered as specifically human EI is an important aspect of human communication. The ability to understand and respond to emotional cues is essential for effective communication. Therefore, it is crucial to determine the ways AI models such as ChatGPT demonstrate EI. The present research aims to measure the EI of GPT-4, a large language model trained by OpenAI. Russian version of the Mayer–Salovey–Caruzo Emotional Intelligence Test sections B, C, D, F, G and H were used in this research. High points were obtained in Understanding emotions scale and Strategic EI. Mean points are obtained in Managing emotions scale. Low and less reliable values are obtained in Using emotions to facilitate thought scale. Thus, GPT-4 seems already capable of identifying emotions in text and describing techniques for managing them. However, complex cases and irregular situations requiring emotions qualitative analysis would be a hard task for GPT-4.

This article presents a kinematic analysis of a 4-degree-of-freedom (DOF) robotic arm equipped with a 3-finger gripper, specifically designed for harvesting fruits of varying sizes. The kinematic modeling is thoroughly detailed, encompassing the equations of motion, homogeneous transformation matrices, and kinematic solutions required for the efficient operation of the robotic arm. This analysis is crucial for optimizing both the design and programming of agricultural robots, aiming to enhance harvesting efficiency and reduce labor costs. Additionally, an in-depth examination of the 3-finger gripper’s movement is provided, illustrating how MATLAB facilitates the simulation and visualization of its dynamic behavior during the opening and closing processes. The benefits of using MATLAB for this purpose are emphasized, including its ease of implementation, advanced simulation capabilities, and seamless integration with other tools to optimize the performance of robotic systems in agricultural settings. This study makes a valuable contribution to the field of agricultural robotics, offering technical insights that can be applied in the development of sophisticated robotic solutions for the modern agricultural industry.

Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Changes during this period could contribute to inflammation and be associated with variations in the vascular smooth muscle (VSMC) phenotype. We studied changes in inflammatory pathways that could underlie the expressions of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. We analyzed histological changes in the aorta and expressions of the COX-2, TLR4, iNOS, eNOS, MMP-2, -9, β-, α-actin, and TNF-α, IL-6 and IL-1β expressions, and fatty acids by gas chromatography. The aortic wall presented disorganization, decellularization, wavy elastic fibers and increase in the lumen area. The COX-2, TLR4 expressions, TNF-α and IL-6 were increased, but iNOS, MMP-2 and -9 tended to increase and eNOS and arachidonic acid tended to decrease, con increase in oleic acid in CP in comparison with control group. There is a transient hypertension at the end of the CP that is accompanied by an inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the hypertension development during adulthood.

GPT-4 was released in March 2023 to wide acclaim, marking a very substantial improvement across the board over GPT-3.5 (OpenAI's previously best model, which had powered the initial release of ChatGPT). Despite the genuinely impressive improvement, however, there are good reasons to be highly skeptical of GPT-4's ability to reason. This position paper discusses the nature of reasoning; criticizes the current formulation of reasoning problems in the NLP community and the way in which the reasoning performance of LLMs is currently evaluated; introduces a collection of 21 diverse reasoning problems; and performs a detailed qualitative analysis of GPT-4's performance on these problems. Based on the results of this analysis, the paper argues that, despite the occasional flashes of analytical brilliance, GPT-4 at present is utterly incapable of reasoning.

Chat generative pre-trained transformer (ChatGPT) is a developed language model and a subgroup of artificial intelligence (AI) which has demonstrated noticeable innovation in interactions between computer models and human studies. The release of ChatGPT in November 2022 attracted over 100 million users in a short time. It has unlimited applications in different fields of studies such as technology and science. ChatGPT utilizes deep learning and internet text to produce responses that resemble human language, although their accuracy is not always guaranteed. ChatGPT and GPT-4 can make a huge revolution in biology, medical, dental research, and health care. However, it's important to acknowledge the limitations of ChatGPT such as limitation in accessing the latest data. ChatGPT has generated both excitement and concern regarding its potential misuse. Its utilization in scientific publications has sparked debates and prompted the development of policies to govern the use of it. Although ChatGPT has certain limitations, it could impact on many different fields of study. There are challenges associated with using ChatGPT in the field of laboratory medicine and biology, particularly in the interpretation of test results. In this article, we review some of the applications of ChatGPT and GPT-4 in biology, dental and medical studies, and concerns about ChatGPT. Despite ChatGPT's conversational abilities are impressive, there are important considerations regarding its use in different fields of research and academic public.

In this research, first a binary nanocomposite of magnetic recyclable photocatalyst Fe₃O₄/TiO₂, was synthesized by sol gel technique. Then, in order to enhance the photocatalytic activity of the synthesized nanocomposite, it was deposited by silver nanoparticles for using in degradation of organic pollutants 2, 4-dichlorophenol (2, 4-DCP) under visible light. A range of analytical techniques including XRD, FESEM/EDX, DRS, VSM and N₂ physisorption were employed to reveal the crystal structure, morphology and property of the nanocomposites. We obtained 32% and 55% degradation of 2, 4-DCP under visible light after 180 min irradiation in the presence of Fe₃O₄/TiO₂ and Fe₃O₄/TiO₂/Ag respectively. Thus, the excellent visible light photocatalytic activity of Fe₃O₄/TiO₂/Ag sample can be attributed to the surface plasmon resonance effect of Ag nanoparticles deposited on Fe₃O₄/TiO₂ nanocomposite.

Cinnamate 4-hydroxylase (C4H) is a cytochrome P450-dependent monooxygenase enzyme that catalyzes a key step in phenylpropanoid metabolism in plants. However, there is very limited information on the function of C4H in medicinal plants. In the present study, the C4H gene from the Ferula pseudalliacea genome (named FpC4H) was cloned and characterized. In addition, the expression levels of FpC4H in the roots, stems, leaves, flowers and seeds were investigated via real-time PCR. FpC4H showed the most similarity with C4H proteins from Daucus carota. The results predicted that FpC4H, as well as its orthologs, is an unstable and hydrophilic protein. A high genetic distance was observed between FpC4H and C4H from monocots based on evolutionary analysis. Moreover, a variable region related to the variable function of C4H was detected in conserved domain region of C4H proteins. Protein structure analysis revealed that isoleucine and leucine residues are frequently present in the binding region of FpC4H, and two ion binding regions, cysteine258 and asparagine217, were identified in the 3D structure of FpC4H. Expression analysis revealed that the FpC4H gene is expressed in all organs of F. pseudallicea. A low expression level of FpC4H was recorded in leaves, and a high expression level was observed in flower tissues. Based on the expression profile, FpC4H seems to be linked to a high content of phenolic compounds in flowers.

In this work, pure TiO₂ and binary nanocomposites of Fe₃O₄/TiO₂ and Ag/TiO₂ were synthesized in order to improve photocatalytic performance of these samples for degradation of 2, 4-dichlorophenol (2, 4-DCP) as an organic pollutant. A range of analytical techniques including XRD, DRS, SEM/EDX, and elemental mapping were employed to reveal the crystal structure, morphology and property of the nanocomposites. XRD data demonstrated that the prepared samples are purely in TiO₂ anatase phase and cubic spinel Fe₃O₄ exist in the synthesized nanocomposite. We calculated the TiO₂ crystal size from XRD patterns, in the range of 8.35-11.09 nm. The presence of Ag, Fe, O, and Ti atoms in the synthesized nanocomposites was confirmed by SEM/EDX. We obtained 30.43, 32.02 and 42.40 % degradation of 2, 4-DCP (100 ml 2, 4-DCP 40 ppm and 0.01 g catalyst) for pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively, after 180 min of irradiation under visible light. Similar conditions were employed for 2, 4-DCP degradation under UV irradiation, we obtained 53.05, 51.00 and 71.50 % degradation of 2, 4-DCP pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively. Thus, the synthesized binary nanocomposites exhibited higher photocatalytic activity compared to pure TiO₂ under visible light.

Zinc cobalt oxide-zinc hydroxide (ZnCo2O4-Zn(OH)2) microspheres were successfully fabricated on carbon cloth via a sample hydrothermal method. The surface morphology of these microspheres and their efficacy in degrading methyl violet were further modulated by varying the thermal annealing temperatures. The manipulation of thermal annealing temperatures was pivotal in adjusting the porosity of ZnCo2O4-Zn(OH)2 microspheres to amplify their photocatalytic performance. Various analytical techniques were utilized to evaluate the physical and chemical properties of the ZnCo2O4-Zn(OH)2 microspheres, including field-emission scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, field-emission transmission electron microscopy, X-ray photoelectron spectroscopy, and UV-vis spectroscopy. Compared to untreated ZnCo2O4-Zn(OH)2 microspheres, those subjected to thermal annealing exhibited increased specific surface area and light absorption capacity, rendering them highly effective photocatalysts under UVC light exposure. Subsequent studies have confirmed the superior performance of ZnCo2O4-Zn(OH)2 microspheres as a reusable photocatalyst for degrading methyl violet and tetracycline. Additionally, trapping experiments during the photodegradation process involving ZnCo2O4-Zn(OH)2 microspheres have identified hydroxyl radicals (·OH) and superoxide radicals (·O2–) as the primary reactive species.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

We successfully fabricated Ag@Cu2O core-shell decorated on reduced graphene oxide (rGO) nanocomposites (ACRN) by a simple and convenient in situ substitution method. The properties of these ACRN with heterostructure layers were characterized by scanning and transmission electron microscopies and absorption spectroscopy. We used p-nitrophenol (4-NP) as a probe molecule to determine the chemical catalytic activity of the ACRN. Upon introduction of rGO, a high electron transfer efficiency was achieved; thus, the catalytic activity was improved significantly. Therefore, the ACRN exhibited significantly improved catalytic activity for the reduction of 4-NP and showed the high application value in the removal of toxic and harmful substances from water. In addition, the fabricated ACRN was used for the reduction of organic dyes and explosive pollutants to generate nontoxic products. Furthermore, the high charge redistribution and transfer among Ag, Cu2O and rGO in the ACRN induced the high catalytic reduction of organic pollutants, indicating the excellent potential of these materials for applications in water pollution treatment.

The authors previously found a model of universal quantum computation by making use of the coset structure of subgroups of a free group $G$ with relations. A valid subgroup $H$ of index $d$ in $G$ leads to a \lq magic' state $\left|\psi\right\rangle$ in $d$-dimensional Hilbert space that encodes a minimal informationally complete quantum measurement (or MIC), possibly carrying a finite \lq contextual' geometry. In the present work, we choose $G$ as the fundamental group $\pi_1(V)$ of an exotic $4$-manifold $V$, more precisely a \lq small exotic' (space-time) $R^4$ (that is homeomorphic and isometric, but not diffeomorphic to the Euclidean $\mathbb{R}^4$). Our selected example, due to to S. Akbulut and R.~E. Gompf, has two remarkable properties: (a) it shows the occurence of standard contextual geometries such as the Fano plane (at index $7$), Mermin's pentagram (at index $10$), the two-qubit commutation picture $GQ(2,2)$ (at index $15$) as well as the combinatorial Grassmannian Gr$(2,8)$ (at index $28$) , (b) it allows the interpretation of MICs measurements as arising from such exotic (space-time) $R^4$'s. Our new picture relating a topological quantum computing and exotic space-time is also intended to become an approach of \lq quantum gravity'.

On average, one in ten patients die because of a diagnostic error and medical errors are the third largest cause of death in the word. While LLMs have been proposed to help doctors with diagnoses, no research results have been published on comparing the diagnostic ability of many popular LLMs on an openly accessible real-patient cohort. In thus study, we compare LLMs from Google, OpenAI, Meta, Mistral, Cohere and Anthropic using our previously published evaluation methodology and explore improving their accuracy with RAG.

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Sever-al lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melano-ma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was acti-vated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells re-vealed stable NGFR mRNA. The combination of both reporters provided insights into pheno-type switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated genes serving as potential drivers of a NGFR-associated phenotype switching in vitro and in relapsed, post-BRAF inhibitor treated tu-mors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plastici-ty and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

CD44 has been known as a marker of tumor initiating cells, and plays pro-tumorigenic functions in many cancers. The splicing variants play critical roles in malignant progression of cancers by promoting the stemness, cancer cell invasion or metastasis, and resistance to chemo- and radiotherapy. To understand each CD44 variant (CD44v) function is essential to know the property of cancers and establishment of the therapy. However, the function of the variant 4-encoded region has not to be elucidated. Therefore, specific monoclonal antibodies (mAbs) against the variant 4 are indispensable for basic research, tumor diagnosis, and therapy. In this study, we established anti-CD44 variant 4 (CD44v4) monoclonal antibodies (mAbs) by immunizing mice with a peptide containing the variant 4-encoded region. We next performed flow cytometry, western blotting, and immunohistochemistry to characterized them. One of the established clones (C₄₄Mab-108; IgG₁, kappa) reacted with CD44v3-10-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44v3-10). The K_D of C₄₄Mab-108 for CHO/CD44 v3-10 was 3.4 × 10⁻⁷ M. In western blot analysis, C₄₄Mab-108 detected CD44v3-10 in the lysate of CHO/CD44v3-10 cells. Furthermore, C₄₄Mab-108 stained formalin-fixed paraffin-embedded oral squamous carcinoma tissues in immunohistochemistry. These results indicated that C₄₄Mab-108 is useful to detect CD44v4 in various applications.

In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4 positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers was noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gallbladder) in comparison to primary tumors. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. Their conversion to 5-substituted -hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted -aminoketones or a single -diketone. The new compounds were characterized by spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

Overweight/obesity and cardiovascular diseases are associated with high rates of mobility and mortality. We investigated inflammatory lesions and ionic transporters in the left ventricle of male rats chronically fed a high-fat diet (HL). They developed moderate overweight with early expansion of visceral adiposity. The inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-), Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles, and the left ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). HL rats doubled IL-6 and TNF-, which returned to normal levels when signaling coupled to Angiotensin II type 2 receptors (AT2R) was supraregulated by Ang-(3–4) administration. The decreased glucose tolerance was accompanied by significantly reduced plasma triglycerides due to intense hepatic steatosis (Crisóstomo et al. Metabolism Open. 2022, 14, 100176). AT2R (and AT1R) abundance did not change. (Na++K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, normalized with Ang-(3–4). SERCA2a lost its most critical regulatory property, inhibition by excess substrate. The ultrasound showed no changes in FS and EF. We conclude that very moderate overweight can cause silent initial molecular tissue damage in heart, which can evolve to cause systolic dysfunction.

The toxic effects of 4-octylphenol (4-OP) have been studied in species such as mouse and fish; however, the toxic effects of 4-OP in male specific niche cells has not been researched. In this study, we investigated the molecular mechanism of toxicity of 4-OP in mouse TM4 Sertoli cells. TM4 cells were treated with four concentrations (0, 10, 30, and 50 µM/mL) of 4-OP at time points 24, 48, and 72 h. Cell viability and apoptosis assay was conducted following exposure. 4-OP significantly decreased cell viability in a concentration- and time-dependent manner, and increased apoptosis. Quantitative PCR analysis showed that Bad, Bax, and Bak mRNA expression levels were higher in exposed cells than in the control, but Bcl-2 expression was decreased. Western blotting revealed that 4-OP induced activities of caspase-3 and phosphorylation of Bad in a concentration- and time-dependent manner. Additionally, cytochrome C protein did not colocalize with mitochondria marker dye by 24 h. Cytochrome c protein expression increased in a time-dependent manner with 50 µM/mL. These results suggest that 4-OP induces mitochondria-mediated apoptosis by regulation of Bcl-2 family proteins and caspase-3 activation in male Sertoli cells.

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

The rapid emergence and worldwide detection of the SARS-CoV-2 omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and more strong vaccine breakthrough ability. Also known as B.1.1.529, Omicron has four sub-variants, BA.1, BA.2, BA.3, and BA.4. Among them, BA.1 is the currently prevailing sub-variant, BA.2 is found to be able to alarmingly re-infect patients initially infected by omicron BA.1. BA.3 sub-variants is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today emerging is the BA.4, herein described and first detected in Italy, harboring a new mutation, specifically a deletion in the ORF 1 ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants pointed out that the deletion was not present previously and was never reported until now. Therefore, we can speculate that omicron BA.4; will become a new dominating “variant of concern” and might also break vaccine protection . On the other hand, we show that other proteins are mutated in the BA.4 in particular, seven mutations are recognized in the nucleocapsid (N) protein, the capability of five different types of rapid antigenic tests to recognize it.

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, Glucagon-Like Peptide-1 Receptor Ag-onists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aimed to investigate how the GLP-1RA Exendin-4 (Ex-4) affects the mi-croRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from untreated, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment path-way analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, in-sulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigations.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

A newly synthesized upper rim azocalix[4]arene, namely, 5,11,17,23-tetra[(4-ethylacetoxyphenyl) (azo)]calix[4]arene, CA-AZ was fully characterized and its chromogenic and selective properties for anions are reported. The receptor is selective for the fluoride anion and its mode of interaction in solution is discussed. The kinetics of the complexation process was found to be very fast as reflected in the immediate color change observed with a naked eye resulting from the receptor-anion interaction. Emphasis is made about the relevance in selecting a solvent in which the formulation of the process is representative of the events taking place in the solution. The composition of the fluoride complex investigated by UV/VIS spectrophotometry, conductance measurements and titration calorimetry was 1:1 and the thermodynamics of complexation was determined. The fluoride complex salt was isolated, and a detailed investigation was carried out to assess its ability to remove CO₂ from the air. Recycling of the complex was easily achieved. Final conclusions are given.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

The prevalent pathogens associated with bovine uterine infections are bacteria that appear to increase the host's susceptibility to secondary infections with other bacteria or viruses, among which BoHV-4 is the most frequently found. In this work, the study of the pathways of apoptosis induction was carried out on an experimental model of primary culture of endometrial cells, in order to know the implication of BoHV-4 and the presence of bacterial LPS in the pathogenesis of the bovine reproductive tract. For this, different staining techniques and molecular analysis by RT-PCR were used. The results obtained allowed us to conclude that the level of cell death observed in the proposed primary culture is directly related to the time of viral infection and the presence of LPS in BoHV-4 infection. The apoptosis indices in cells infected with BoHV-4, BoHV-4 + LPS presented a maximum that correlates with the appearance of the cytopathic effect, and the maximum viral titers in the model studied. However, morphological, biochemical and molecular changes were evident during both early and late stages of apoptosis. These findings provide information on the factors that may influence the pathogenesis of BoHV-4 and help to better understand the mechanisms involved in virus infection.

Cartilage regeneration requires a balance of anabolic and catabolic processes. This study examined the susceptibility of fibromodulin (FMOD) and lumican (LUM) to degradation by MMP-13, ADAMTS-4 and ADAMTS-5, the three major degradative proteinases in articular cartilage in osteoarthritis (OA). Immunolocalisation of FMOD and LUM in foot sections of developmental cartilages demonstrated prominent localisations in metatarsal and phalangeal foetal rudiment cartilages and growth plate. An MMP-13 neoepitope antibody (TsYG11) demonstrated localisation of MMP-13 cleaved FMOD in the hypertrophic chondrocytes of the metatarsal growth plate. FMOD was more prominently localised in the superficial cartilage of normal and fibrillated zones in OA cartilage, TsYG11 positive FMOD was located deeper in the cartilage samples. Ab TsYG11 also identified FMOD fragmentation in Western blots of extracts of normal and fibrillated cartilage and total knee replacement OA cartilage. The C-terminal anti-FMOD used in this study (PR-184) failed to identify FMOD fragmentation due to C terminal processing, an equivalent Ab to the C-terminus of LUM (pAb PR-353) identified 3 prominent LUM fragments in OA human knee cartilages. In-vitro digestion of human knee cartilage with MMP-13, ADAMTS-4 and ADAMTS-5 generated equivalently sized FMOD fragments of 54, 45 and 32kDa to those in blots of OA cartilage, LUM was not less susceptible to fragmention in in-vitro digestions however Ab PR-353 detected N-terminally processed LUM fragments of 39, 38 and 22 kDa in 65-80 year old OA knee cartilage. FMOD and LUM were differentially processed during in-vitro digestions with MMP-13, ADAMTS-4 and ADAMTS-5 with FMOD susceptible to degradation by MMP-13, ADAMTS-4 and to a lesser extent ADAMTS-5 however LUM was less susceptible to fragmentation. FMOD was processed by MMP-13 in metatarsal and phalangeal foetal rudiment developmental cartilages and growth plate indicating a role in skeletogenesis.

There is an urgent need to better understand the mechanisms involved in scar formation in brain. It is well known that astrocytes are critically engaged in this process. Here we analyze in-cipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mo-bility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.

In this study, unlike conventional methods for producing vanadium (3.5+) electrolyte by VOSO4 and V2O5, a batch-type hydrothermal reactor was used to produce a vanadium (3.5+) electrolyte for vanadium redox flow batteries through a reduction reaction. The starting material, V2O5, was mixed with different concentrations of citric acid (0.8M, 1.2M, 1.6M, 2.0M) as reducing agent and stirred using a hot plate at 90°C for 60 minutes to achieve complete dispersion in the solution. The resulting solution was then subjected to a hydrothermal reduction reaction in a furnace at 150°C for 24 hours to produce vanadium (3.5+). The mixed state of the produced vanadium (3+) and vanadium (4+) was confirmed using UV-vis spectroscopy. Electrochemical properties were investigated through CV analysis, confirming that the optimal concentration was 1.6M. Charge and discharge experiments were conducted to compare the current efficiency, energy efficiency, and voltage efficiency of the electrolyte prepared by the hydrothermal reduction process and the electrolyte prepared by VOSO4. As a result, the electrolyte produced through the hydrothermal reduction process showed improved performance in all efficiencies. The results shows that vanadium (3.5+) electrolyte could be easily produced through a reaction process using citric acid.

The emergence of resistance to first-line antimalarial drugs calls for development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on Plasmodium falciparum strains: IC50 values after a 48-hour cycle ranged from 0.60 - 49 µM, while the 72-hour cycle ranged from 26-219 nM on the multi-drug resistant K1 strain. Time-course assays were carried out to define the activity of the lead compounds which inhibited over 50 % growth in 24 hours and 90% growth in 72 hours. Cytotoxicity assays with HepG2 cells showed IC50 values of 0.87-11.1 M, whereas in MDBK cells IC50 values ranged from 1.66-11.7 M. High selectivity indices were observed for the lead compounds screened at 72 hours on P. falciparum. Analyses of stage-specificity revealed that the ring stage of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC90 for the combination of with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2) which maintained similar activity to K1, suggesting no cross-resistance between multi-drug resistance and sensitive parasite strains. In vivo analysis with 2 showed suppression of parasitaemia with P. yoelii NL treated mice (20 mg/kg and 5 mg/kg).

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.

A study has been carried out on Ta and Nb recovery by liquid-liquid extraction process using 4-methylacetophenone (4-MAcPh) as organic phase. The 4-MAcPh was compared to methylisobutylketone (MIBK) with respect to extraction efficiencies (kD values) at different concentrations of H2SO4 in the aqueous phase. The results showed a similar extraction of Nb for both solvents. However, for Ta extraction efficiency is increased by a factor of 1.3 for 4-MAcPh. In addition, the MIBK solubilized completely after 6 mol L-1 of H2SO4 against only a loss of 0.14 to 4% for 4-MAcPh between 6 and 9 mol L-1 of H2SO4. The potential of 4-MAcPh has also been studied to selectively recover Ta from a model capacitor waste solution. The results showed a selectivity for Ta in the presence of impurities such as Fe, Ni, Mn. The 4-MAcPh also presents the advantage of having physicochemical properties adapted to its use in liquid-liquid extraction technologies such as mixer-settlers.

Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understand the process of inflammation and tissue regeneration. To this end, we have investigated the interactions of Interleukin-4 cytokine (IL-4)/Interleukin-4 cytokine receptor (IL-4R) and Interleukin-10 cytokine (IL-10)/Interleukin-10 cytokine receptor (IL-10R) using in situ Proximity Ligation Assays in a regenerative model of skin, muscle and lung tissues in the mini-pig. The pattern of protein-protein interactions was distinct for the two cytokines. IL-4 bound predominantly to receptors on macrophages and endothelial cells around the blood vessels while the target cells of IL-10 were mainly receptors on muscle cells. Our results show that in situ studies of cytokine-receptor interactions can provide unravel the fine details of the mechanism of action of cytokines.

Bacterial infections are world-wide problem and resistant bacteria is increasing globally that lead to treatments failure. Thus, it is important to find new techniques that are effective for the treatment antibiotic-resistant microorganisms. Green medicine used for the medication of different bacterial infection. Therefore , the study aimed to evaluate the immunomodulatory activity of essential fatty acid semi carbazide (EFASC) compounds extracted from flaxseed to eradicate resistance pathogens . Crud extracts of Linum usitatissimum was extracted by hexane for extraction of EFASC. The results of LD₅₀ appear that a live suspension of E.coli was 0.49×10⁷ ,while HK E.coli was 10⁸ , 125 mg /ml were the optimum dose in stimulate immune response of EFASC which gave maximum dose of total WBC , Neutrophil and Monocyte count. The immunomodulatory activity appear that E.coli + EFASC released moderate levels of IL-4 . HK E.coli release higher IL-4 lead to increase the hypersensitivity and hyper responses of immune system. HK + EFASC immunogen revealed moderate increased in IL-12 mean level 0.99 pg /ml, HK bacteria recorded 1.49 pg/ml, while the mean of EFASC revealed no significant different compare with control. An effective protection was observed in immunized groups with HK E.coli and EFASC challenged with 100 of LD50 of a live E.coli.

Crataegus Oxyacantha is used in the treatment of cardiovascular diseases. In related to your biosafety, only in vitro and in vivo genotoxicity of the fruit and the leaf is described, however, the teratogenic potential is unknown. The aim this study was evaluating the transplacental genotoxicity effect of aqueous and hydroalcoholic extract of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in liver. Three different doses of the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), sampling in rats were every 24 h during the last 6 days of gestation and only one sample was taken in neonates at birth. A sample of the mother's and neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the aqueous and hydroalcoholic extract generated cytotoxic and genotoxic damage in the short term. On the other hand, only the aqueous extract showed a teratogenic effect. Based on these results, the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf should not be administered during pregnancy.

(1) Background: The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and disease activity and organ mani-festations in SLE patients. (2) Methods: We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4, and interleukin-6 (IL-6) levels, and antinu-clear and antiphospholipid antibody profiles. (3) Results: The median serum levels of sTfR (p>0.000001) and IL-4 (p<0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p<0.0001), a lower iron concentration (p=0.008), a lower value of total iron-binding capacity (TIBC) (p=0.03), and lower counts of RBC (p=0.004), HCT (p=0.0004), PLT (p=0.04), neutrophil (p=0.04), and lymphocyte (p<0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p=0.0005), HGB (p=0.0001) and HCT (p=0.008), and positively correlated with IL-4 (p=0.01). Elevated serum sTfR >2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71–464.78; p=0.001), ischemic heart disease (OR: 3.25 95 CI 1.02–10.40; p=0.04), lung manifestations (OR: 4.48 95 CI 1.44–13.94; p=0.01), and hematological manifestations (OR: 2.07 95 CI 1.13–3.79; p=0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22–0.80; p=0.008). Serum IL-4 was negatively correlated with CRP (p=0.003), and elevated serum IL-4 levels > 0.17 mg/l were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26–0.90; p=0.02). (4) Conclusions: In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation of the sulfonated metabolite of salbutamol, reference material was synthesized and characterized by NMR and HRMS. Urine samples were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Salbutamol is mainly metabolized by sulfotransferase 1A3 (SULT1A3), which is most abundantly found in the jejunum. A high first pass effect occurs upon oral administration, which leads to a higher amount of salbutamol-4’-O-sulfate in urine compared to unchanged salbutamol excreted within the first hour post administration. Thus, when administered orally, the proportion of metabolite to total salbutamol was higher than for inhalative administration in the early urinary excretion. Levosalbutamol is the favored enantiomer of SULT1A3 and therefore metabolized at a higher rate whereas racemic salbutamol shows a reduced proportion between metabolite and parent compound. The amount of sulfoconjugate was found higher than that of the parent compound for all urine samples except for those excreted in the first hour after inhalative administration.

Boeremia exigua var. exigua is a recurrent pathogen causing root rot in industrial chicory. Currently, there is no chemical or varietal control for this disease, and thus management strategies need to be developed. This study determined the biocontrol effect of strains of Pseudomonas protegens bacteria with antimicrobial compounds on the fungus B. exigua var. exigua under in vitro, in vivo and field conditions. In addition, root colonization by these bacteria was estimated by molecular analysis. Eighteen isolates of Pseudomonas spp were evaluated and the strains that showed the greatest in vitro inhibition of fungal mycelial growth (mm), Ca10A and ChB7, were selected. Inoculation with the strain ChB7 showed less severity (necrotic area) under in vivo conditions (root trials) compared to the control inoculated with the pathogen (P≤0.05). The molecular analysis revealed that root colonization of plants grown in pots was equal or greater than 70%. Similar levels were observed in the field trials conducted in Selva Negra and Canteras experimental stations (2015-16 season), with values ranging from 85.7 to 70.5% and from 75.0 to 79.5%, respectively. Regarding yield (ton ha-1), values were higher in the treatments inoculated with strains Ca10A and ChB7 (P≤0.05) in both experimental sites, while a lower incidence and severity of root rot were observed in Selva Negra. These results suggest that the Chilean strains of P. protegens are a promising tool for the control of root diseases in industrial chicory.

A novel synthetic strategy is disclosed to prepare a new class of metalorganic copolymers which contain iron(II) clathrochelate building blocks by employing a mild and cost-effective copper-catalyzed [4 + 2] cyclobenzannulation reaction, using three specially designed diethynyl iron(II) clathrochelate synthons. The target copolymers CBP1-3 were isolated in high purity and excellent yields as proven by their structural and photophysical characterization, namely, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and UV-vis absorption and emission spectroscopies. Thermogravimetric analysis (TGA) of CBP1-3 reveals excellent chemical stability. Investigation of the adsorption properties of the target copolymers towards the carcinogenic methyl red dye from aqueous solution reveals a quantitative uptake in 30 minutes. Isothermal adsorption studies disclose that methyl red uptake from aqueous solution follows Langmuir model for all the target copolymers reaching a maximum adsorption capacity (qm) of 431 mg g‒1, whereas kinetic investigation reveals that the adsorption follows pseudo first-order with an equilibrium adsorption capacity (qe,cal) of 79.35 mg g‒1 and whose sorption property was sustained even after its reuse several times.

Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The aim of the present study was to assess the impact of pretreatment serum levels of 27 selected cytokines on progression-free survival (PFS) and overall survival (OS) in MM patients before first-line therapy with bortezomib-based regimens. Serum cytokine levels were assayed with a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad) including IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. A total of 61 MM patients were examined. Most patients received a bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy regimen. In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240-0.8291, p = 0.0302), and ASCT (HR 0.3722, 95% CI: 0.1826-0.7585, p=0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046-0.438, p=0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471-9.949, p=0.0059) and two cytokine levels- IL-1Ra (HR 1.017, 95% CI: 1.004-1.030, p= 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037-0.698, p = 0.0147) were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.

Trigonella foenum is one of the oldest medicinal plants that grow in many parts of Iran with the diverse ecological situation. Employing this plant for treating diabetes and high cholesterol has a long history, because of some metabolites. Due to the habitat of fenugreek is a wide range of climatic conditions, it may have power to cope with climate variation. The main intention of this inquiry was to understand the effect of the environmental variables on this therapeutic plant features. It was also interesting for us to understand which environment variables are more impressive for enhancing of trigonelline and 4-hydroxy isoleucine content as the most important metabolites of this plant. For achieving this goal, environmental information and vegetal data were analyzed to discover the role of nature on the seed part of fenugreek life in 50 different regions of Iran. Canonical correspondence analysis (CCA) displayed that high content of metabolites and some morphological characteristics happened in high temperature and solar irradiation. Partial least squares regression (PLSR) and path analysis used to find the best predictors and direct and indirect effect of all variables on 4-hydroxy isoleucine and trigonelline. Ecological condition were the best predictors and had the highest direct and indirect impact on 4-hydroxy isoleucine. However, for trigonelline, the environment did not play a senior role. It seems that the reaction of components of fenugreek does not follow the same way. Studying on morphological, primary and secondary metabolites, and surrounding environment of fenugreek, helped us to have a more precise judgment about the life of this plant.

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.

Binderless zeolite macrostructures in the form of ZK-4 microspheres were prepared using anion exchange resin beads as shape directing macrotemplates. The particles were synthesized under hydrothermal conditions at different temperatures and treatment times. The influence of the different synthesis parameters was investigated by X-ray diffraction, scanning electron microscopy, fluorescence X, nitrogen adsorption measurements and ²⁹Si solid NMR. Fully crystalline spheres similar in size and shape to the original resin beads were obtained by a hydrothermal treatment at the highest temperatures (150 - 180 °C) for a short treatment time of 24 h. The synthesized microspheres showed to be promising in the molecular decontamination of Volatile Organic Compounds (VOCs).