Characterizing the effects of muscle-specific GSK3α/ß reduction on murine muscle contractility and metabolism in female mice.

Dysregulation of skeletal muscle morphology and metabolism is associated with chronic diseases such as obesity and type 2 diabetes. The enzyme glycogen synthase kinase 3 (GSK3) is highly involved in skeletal muscle physiology and metabolism, acting as a negative regulator of muscle size, strength, adaptive thermogenesis, and glucose homeostasis. Correspondingly, we have shown that partial knockdown (∼40%) of GSK3 specifically in skeletal muscle increases lean mass, reduces fat mass, and activates muscle-based adaptive thermogenesis via sarco(endo)plasmic reticulum Ca2+ (SERCA) uncoupling in male mice. However, the effects of GSK3 knockdown in female mice have yet to be investigated. Here, we examined the effects of muscle-specific GSK3 knockdown on body composition, muscle size and strength, and whole body metabolism in female C57BL/6J mice. Our results show that GSK3 content is higher in the female soleus versus the male soleus; however, there were no differences in the extensor digitorum longus (EDL). Furthermore, muscle-specific GSK3 knockdown did not alter body composition in female mice, nor did it alter daily energy expenditure, glucose/insulin tolerance, mitochondrial respiration, or the expression of the SERCA uncouplers sarcolipin and neuronatin. We also did not find any differences in soleus muscle size, strength, or fatigue resistance. In the EDL, we found that an increase in absolute and specific force production, but there were no differences in fatigability. Therefore, our study highlights sex differences in the response to genetic reduction of gsk3, with most of the effects previously observed in male mice being absent in females.NEW & NOTEWORTHY Here we show that partial GSK3 knockdown has minimal effects on whole body metabolism and muscle contractility in female mice. This is partly inconsistent with previous results found in male mice, which reveal a potential influence of biological sex.

Estrogens dynamically regulate neurogenesis in the dentate gyrus of adult female rats.

Estrone and estradiol differentially modulate neuroplasticity and cognition. How they influence the maturation of new neurons in the adult hippocampus, however, is not known. The present study assessed the effects of estrone and estradiol on the maturation timeline of neurogenesis in the dentate gyrus (DG) of ovariectomized (a model of surgical menopause) young adult Sprague-Dawley rats using daily subcutaneous injections of 17ß-estradiol, estrone or vehicle. Rats were injected with a DNA synthesis marker, 5-bromo-2-deoxyuridine (BrdU), and were perfused 1, 2, or 3 weeks after BrdU injection and daily hormone treatment. Brains were sectioned and processed for various markers including: sex-determining region Y-box 2 (Sox2), glial fibrillary acidic protein (GFAP), antigen kiel 67 (Ki67), doublecortin (DCX), and neuronal nuclei (NeuN). Immunofluorescent labeling or co-labelling of BrdU with Sox2 (progenitor cells), Sox2/GFAP (neural progenitor cells), Ki67 (cell proliferation), DCX (immature neurons), NeuN (mature neurons) was used to examine the trajectory and maturation of adult-born neurons over time. Estrogens had early (1 week of exposure) effects on different stages of neurogenesis (neural progenitor cells, cell proliferation and early maturation of new cells into neurons) but these effects were less pronounced after prolonged treatment. Estradiol enhanced, whereas estrone reduced cell proliferation after 1 week but not after longer exposure to either estrogen. Both estrogens increased the density of immature neurons (BrdU/DCX-ir) after 1 week of exposure compared to vehicle treatment but this increased density was not sustained over longer durations of treatments to estrogens, suggesting that the enhancing effects of estrogens on neurogenesis were short-lived. Longer duration post-ovariectomy, without treatments with either of the estrogens, was associated with reduced neural progenitor cells in the DG. These results demonstrate that estrogens modulate several aspects of adult hippocampal neurogenesis differently in the short term, but may lose their ability to influence neurogenesis after long-term exposure. These findings have potential implications for treatments involving estrogens after surgical menopause.

Investigating the chemo-preventive role of noscapine in lung carcinoma via therapeutic targeting of human aurora kinase B.

Lung carcinoma is the major contributor to global cancer incidence and one of the leading causes of cancer-related mortality worldwide. Irregularities in signal transduction events, genetic alterations, and mutated regulatory genes trigger cancer development and progression. Selective targeting of molecular modulators has substantially revolutionized cancer treatment strategies with improvised efficacy. The aurora kinase B (AURKB) is a critical component of the chromosomal passenger complex and is primarily involved in lung cancer pathogenesis. Since AURKB is an important therapeutic target, the design and development of its potential inhibitors are attractive strategies. In this study, noscapine was selected and validated as a possible inhibitor of AURKB using integrated computational, spectroscopic, and cell-based assays. Molecular docking analysis showed noscapine occupies the substrate-binding pocket of AURKB with strong binding affinity. Subsequently, MD simulation studies confirmed the formation of a stable AURKB-noscapine complex with non-significant alteration in various trajectories, including RMSD, RMSF, Rg, and SASA. These findings were further experimentally validated through fluorescence binding studies. In addition, dose-dependent noscapine treatment significantly attenuated recombinant AURKB activity with an IC50 value of 26.6 µM. Cell viability studies conducted on A549 cells and HEK293 cells revealed significant cytotoxic features of noscapine on A549 cells. Furthermore, Annexin-PI staining validated that noscapine triggered apoptosis in lung cancer cells, possibly via an intrinsic pathway. Our findings indicate that noscapine-based AURKB inhibition can be implicated as a potential therapeutic strategy in lung cancer treatment and can also provide a novel scaffold for developing next-generation AURKB-specific inhibitors.

Clinical and inflammatory features of traffic-related diesel exposure in children with asthma.

BACKGROUND: Epidemiologic studies have revealed associations between traffic-related pollutants such as diesel particulate matter (PM) and asthma outcomes in children, but the inflammatory features associated with diesel PM exposure in children with asthma are not understood. OBJECTIVE: To evaluate symptoms, exacerbations, and lung function measures in children with uncontrolled asthma and their associations with residential proximity to major roadways and to determine associations between diesel PM exposure and systemic inflammatory cytokines, circulating markers of T-cell activation and exhaustion, and metabolomic features using biomarker studies. METHODS: Children 5 to 17 years of age with physician-diagnosed, uncontrolled asthma despite treatment with an asthma controller medication completed a research visit involving questionnaires, lung function testing, and venipuncture for biomarker studies. Geocoding was performed to quantify residential proximity to major roadways and pollutant exposure. RESULTS: A total of 447 children with uncontrolled asthma were enrolled. Children living closer to highly trafficked roadways were more disadvantaged and had more exposure to diesel PM, more exacerbations prompting an emergency department visit, and lower lung function measures. Children with the highest diesel PM exposure, compared with children with the lowest diesel PM exposure, also had blunted cytokine secretion and evidence of T-cell exhaustion, including disturbances in several metabolites associated with glutathione formation and oxidative stress. CONCLUSION: Traffic-related diesel PM exposure in children with poorly controlled asthma is associated with poorer clinical outcomes and unique patterns of inflammation and oxidative stress. These findings argue for continued mitigation efforts to improve traffic-related air quality and health equity in children with asthma.

Assessment of antidiabetic, anti-inflammatory, antioxidant and anticancer activity competence of methonolic extracts of Trianthema ortulacastrum and Andrographis paniculata.

An in-vitro investigation was performed to evaluate and compare the phytochemical, antioxidant, antidiabetic, anti-inflammatory, and anti-lung cancer activities of methanol extracts of aerial parts of Andrographis paniculata and Trianthema portulacastrum. Furthermore studied major functional groups of phytochemicals present in the methanol extracts of these plants through Fourier transform infrared (FTIR) analysis. The results showed that the methanol extract of A. paniculata contain more number of pharmaceutically valuable phytochemicals such as alkaloids, flavonoids, terpenoids, saponin, glycoside, phytosterol, and tannin than T. portulacastrum. Similar way the methanol extract of A. paniculata showed considerable dose dependent antioxidant (DPPH: 63%), antidiabetic (α-amylase: 82.31% and α-glucosidase inhibitions: 72.34%), and anti-inflammatory (albumin-denaturation inhibition: 76.3% and anti-lipoxygenase: 61.2%) activities (at 900 µg mL-1 concentration) than T. portulacastrum. However, the anti-lung cancer activities of these test plants against A549 cells were not considerable. According to FTIR analysis, the A. paniculata methanol extract has a larger number of characteristic peaks attributed to the active functional groups of pharmaceutically valuable bioactive components that belong to different types of phytochemicals. These findings imply that A. paniculata methanol extracts can be used for additional research, such as bioactive compound screening and purification, as well as assessing their potential biomedical uses in various in-vitro and in-research settings.

Kinetics analysis of PAHs degradation using SiO2-ZnO nanoparticles and evaluating their antibacterial and antibiofilm efficacy.

The adsorption of Polycyclic aromatic hydrocarbons (PAHs) using nanoparticles is gaining significant attention due to the rapid removal or treatment rates. In this study, Silicon Dioxide-Zinc Oxide nanoparticles (SiO2-ZnO NPs) were synthesized to adsorb pyrene. Physicochemical characterization of SiO2-ZnO NPs showed plasmon resonance at 323 nm, agglomeration, irregular dispersion, and diameters of 90-100 nm. FT-IR analysis identified major functional groups on SiO2-ZnO NPs, including alkyne, amine, and isothiocyanate. SiO2-ZnO NPs demonstrated significant pyrene adsorption at pH 5, with 10 µg/mL of SiO2-ZnO NPs and 2 µg/mL of PAHs, performing better under UV irradiation. Two isotherm models, adsorption isotherm and kinetics adsorption, were used to analyze the PAHs adsorption by SiO2-ZnO NPs. Additionally, SiO2-ZnO NPs were tested for antibacterial and antibiofilm activities against both Gram-negative and Gram-positive bacteria. At a concentration of 150 µg/mL, SiO2-ZnO NPs produced inhibition zones of 21.57 mm, 20.30 mm, 19.30 mm, and 11.30 mm against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Klebsiella pneumoniae, respectively. They also inhibited and disrupted biofilms of Micrococcus luteus and Acinetobacter baumannii. Furthermore, SiO2-ZnO NPs exhibited photocatalytic degradation of lead, achieving 68.24% degradation within 5 h of treatment. Therefore, SiO2-ZnO NPs are efficient candidates for multiple applications, including pyrene adsorption, bacterial biofilm disruption, and lead degradation under sunlight.

Antimicrobial and anti-diabetic efficiency of Polyalthia longifolia leaf extracts and major compounds characterization.

This research was performed to investigate the bactericidal and fungicidal competence of extracts (methanol and petroleum ether extract) of Polyalthia longifolia leaf. Moreover, the major active compounds present in the effective crude extract (either methanol or petroleum ether extract) was determined through initially with UV-Vis spectra, FTIR, and GC-MS analyses. The methanol extract alone showed remarkable bactericidal and fungicidal activity against the bacterial (S. pyogenes > E. coli > S. aureus > S. pneumoniae > C. difficile > P. aeruginosa) and fungal (A. clavatus > C. albicans > A. niger > A. fumigatus > C. tropicalis > C. auris) pathogens at increased concentration (12.5 mg mL-1) than petroleum ether extract. The MIC and MBC values of methanol extract were found as 10-20 mg mL-1 and 30-40 mg mL-1 respectively. The MFC value of methanol extract was found as 10-20 mg mL-1. These MIC, MBC, and MFC values of methanol extract were considerably greater than petroleum ether extract. The FTIR and GC-MS characterization studies revealed that the presence of more acre functional groups belonging to bioactive compounds such as Z)-7-Hexadecenal, Aromandendrene, α-Curcumene, Caryophyllene, Methyl 14-methyl Pentadecanoat, Methyl trans-13-Octadecenoate, 9-Octadecenoic acid (Z)-, and 2-hydroxy-1- (hydroxymethyl)ethyl. As a result of these findings, it is possible that P. longifolia leaf methanol extract contains medicinally important bioactive substances with bactericidal and fungicidal properties.

Angiogenic protein profiling, phytochemical screening and in silico anti-cancer targets validation of stem, leaves, fruit, and seeds of Calotropis procera in human liver and breast cancer cell lines.

The main focus of anticancer drug discovery is on developing medications that are gentle on normal cells and should have the ability to target multiple anti-cancer pathways. Liver cancer is becoming a worldwide epidemic due to the highest occurring and reoccurring rate in some countries. Calotropis procera is a xerophytic herbal plant growing wildly in Saudi Arabia. Due to its anti-angiogenic and anticancer capabilities, "C. procera" is a viable option for developing innovative anticancer medicines. However, no study has been done previously, to discover angiogenic and anti-cancer targets which are regulated by C. procera in liver cancer. In this study, leaves, stems, flowers, and seeds of C. procera were used to prepare crude extracts and were fractionated into four solvents of diverse polarities. These bioactivity-guided solvent fractions helped to identify useful compounds with minimal side effects. The phytoconstituents present in the leaves and stem were identified by GC-MS. In silico studies were done to predict the anti-cancer targets by major bioactive constituents present in leaves and stem extracts. A human angiogenesis antibody array was performed to profile novel angiogenic targets. The results from this study showed that C. procera extracts are an ideal anti-cancer remedy with minimum toxicity to normal cells as revealed by zebrafish in vivo toxicity screening assays. The novel antiangiogenic and anticancer targets identified in this study could be explored to design medication against liver cancer.

Poly-vinyl-pyrrolidone capped luminescent zinc oxide nanocomposites as excellent tools for germicidal and photo-catalytic performances.

Alternate antibiotics developed through the involvement of nanomaterials are gaining interest due to their economical and lower toxicity concerns. A newly developed biopolymer-based polyvinylpyrrolidone/zinc oxide (PVP/ZnO) nanocomposite (NCs) was efficiently synthesized by an environment-friendly approach, utilizing onion and garlic peel extract as a bio-surfactant, zinc acetate as the source, PVP as the stabilizing agent, and sodium hydroxide as the precipitant. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) investigations verified the crystalline properties of ZnO, PVP, and PVP/ZnO-based NCs. The structure of the biopolymer-linked ZnO particles interpolated inside the PVP array was seen to have a layered and flaky structure, as validated by field emission scanning electron microscopy (FE-SEM) analysis, which revealed its occurrence in the nanometer range. The XRD examination verified that the surface topographical image of PVP/ZnO NCs had an average thickness of 21 nm. The PVP/ZnO nanocrystals demonstrated exceptional photocatalytic efficacy, with a breakdown rate of 88% and almost 92% for the methylene blue dye. Therefore, the PVP/ZnO matrix exhibits superior antibacterial activity compared to other extracts, resulting in greater microbial suppression. The results above indicate that the ZnO-intercalated PVP array has a stronger reinforcing effect than other components. Hence, PVP/ZnO nanocrystals exhibit enormous potential as a favorable substance for environmental and biomedical intentions.

Coconut husk waste products valorization for fabrication of luminescent titanium dioxide NPs as powerful tool for photodecomposition and food born infection: A sustainable strategy.

Fabricating metal oxide nanoparticles has garnered much attention lately because creating safe chemicals, sustainable materials, economic processes, and renewable resources is becoming increasingly important. This research shows how TiO2 nanoparticles (NPs) could be generated in an ecologically responsible way using waste coconut husk with the help of tender coconut. This extract functions as both a reducing agent and a sealing agent. The investigation of TiO2 NPs exploited ultraviolet (UV), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and field-emission scanning electron microscopy (FE-SEM) with energy-dispersive X-ray (EDX) methods. The germicidal properties of TiO2 NPs against food-borne pathogenic strains were studied using the agar well method. Employing Congo red pigment, the photodecomposition behavior was investigated. The TiO2 NPs produced had a crystallite size measuring 16.2 nm. The average grain size of the sample, as measured by FE-SEM inspection, falls within the range of 15 to 25 nm. Impressive anti-germ effects against food-borne germs like Gram-positive (Staphylococcus aureus and Listeria monocytogenes), Gram-negative (Salmonella typhimurium and Escherichia coli) bacteria, and fungi (Candida albicans and Aspergillus niger) have been proved by the sustainable fabrication of TiO2 NPs. The catalytic effectiveness of Congo red decreased by 88% after 90 min. The findings suggest that sustainable synthesis of TiO2 NPs is an effective tool for food-borne germicides and photodecomposition behaviors.

Visible-light enhanced tetracycline degradation via SnO2/TiO2-Ni@rGO ternary heterostructures.

This study explores the synthesis, characterization, and photocatalytic performance of a SnO2/TiO2-Ni@rGO nanocomposite for tetracycline (TC) degradation under visible light irradiation. The nanocomposite was precisely designed to enhance structural stability, charge transfer efficiency, and catalytic activity. X-ray diffraction (XRD) analysis confirmed the structural integrity of the SnO2/TiO2-Ni@rGO composite, demonstrating excellent reusability and resistance to photo-corrosion after multiple cycles. Photocatalytic experiments revealed that the SnO2/TiO2-Ni@rGO nanocomposite significantly outperformed individual SnO2/TiO2-Ni and rGO catalysts, achieving a remarkable 94.6% degradation of TC within 60 min. The degradation process followed pseudo-first-order kinetics, with a rate constant (k) of 0.046 min-1. The Z-scheme charge transfer mechanism facilitated efficient separation and migration of photogenerated charge carriers, generating reactive oxygen species such as superoxide (•O2 -) and hydroxyl (•OH) radicals crucial for the oxidation of TC. Radical scavenger studies confirmed that superoxide and hydroxyl radicals were the primary active species. The SnO2/TiO2-Ni@rGO composite also exhibited excellent reusability, maintaining high catalytic performance over four consecutive cycles. These findings suggest that the SnO2/TiO2-Ni@rGO nanocomposite is a promising candidate for the efficient and sustainable photocatalytic degradation of persistent organic pollutants like TC, offering significant potential for environmental remediation applications.

Synthesis and characterization of fluorinated graphene oxide nanosheets derived from Lissachatina fulica snail mucus and their biomedical applications.

The modern nanomedicine incorporates the multimodal treatments into a single formulation, offering innovative cancer therapy options. Nanosheets function as carriers, altering the solubility, biodistribution, and effectiveness of medicinal compounds, resulting in more efficient cancer treatments and reduced side effects. The non-toxic nature of fluorinated graphene oxide (FGO) nanosheets and their potential applications in medication delivery, medical diagnostics, and biomedicine distinguish them from others. Leveraging the unique properties of Lissachatina fulica snail mucus (LfSM), FGO nanosheets were developed to reveal the novel characteristics. Consequently, LfSM was utilized to create non-toxic, environmentally friendly, and long-lasting FGO nanosheets. Ultraviolet-visible (UV-vis) spectroscopy revealed a prominent absorbance peak at 235 nm. The characterization of the synthesized FGO nanosheets involved X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM), and atomic force microscopy (AFM) analyses. The antimicrobial activity data demonstrated a broad spectrum of antibacterial effects against Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The cytotoxicity efficacy of LfSM-FGO nanosheets against pancreatic cancer cell line (PANC1) showed promising results at low concentrations. The study suggests that FGO nanosheets made from LfSM could serve as alternate factors for in biomedical applications in the future.

Functional immunophenotyping of blood neutrophils identifies novel endotypes of viral response in preschool children with recurrent wheezing.

BACKGROUND: Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population. OBJECTIVE: We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n = 16; no sensitization, n = 36). METHODS: Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid [poly(I:C)] as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase, and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation. RESULTS: A total of 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (ie, more myeloperoxidase and extracellular DNA) and less neutrophil proinflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (ie, M2) phenotype in sensitized children and a more proinflammatory (ie, M1) phenotype in nonsensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled health care were also higher in children without aeroallergen sensitization after enrollment. CONCLUSIONS: Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at type 2-high inflammation.

Exacerbation-prone pediatric asthma is associated with arginine, lysine, and methionine pathway alterations.

BACKGROUND: The asthma of some children remains poorly controlled, with recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and only a limited understanding of the potential underlying mechanisms. OBJECTIVE: We sought to quantify small molecules in the plasma of children with exacerbation-prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation-prone asthma. METHODS: Plasma metabolites were extracted from 4 pediatric asthma cohorts (215 total subjects, with 41 having exacerbation-prone asthma) and detected with a mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects receiving high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. MetaboAnalyst software was used to identify pathways of interest. Concentrations were calculated by reference standardization. RESULTS: We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted. CONCLUSIONS: Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.

Synthesis of bis(2-aminoethyl)amine functionalized mesoporous silica (SBA-15) adsorbent for selective adsorption of Pb2+ ions from wastewater.

Rapid growth in the industry has released large quantities of contaminants, particularly metal discharges into the environment. Heavy metal poisoning in water bodies has become a major problem due to its toxicity to living organisms. In this study, we developed a 3-chloropropyl triethoxysilane incorporated mesoporous silica nanoparticle (SBA-15) based adsorbent utilizing the sol-gel process and Pluronic 123 (P123) as a structure-directing surfactant. Furthermore, the produced SBA-15 NPs were functionalized with bis(2-aminoethyl)amine (BDA) using the surface grafting approach. The physical and chemical properties of the prepared SBA-15@BDA NPs were determined using a variety of instruments, including small-angle X-ray diffraction (SAXS), Fourier-transform infrared (FTIR), scanning electron microscope (SEM), N2 adsorption-desorption, thermogravimetric, particle size distribution, and zeta potential analysis. The MSN has a large surface area of up to 574 m2/g, a pore volume of 0.57 cm3/g, and a well-ordered mesoporous nanostructure with an average pore size of 3.6 nm. The produced SBA-15@BDA NPs were used to adsorb selectively to lead (Pd2+) ions from an aqueous solution. The adsorption study was performed under various conditions, including the influence of solution pH, adsorbent dose, adsorption kinetics, adsorption selectivity in the presence of competing metal ions, and reusability. The results of the kinetic study demonstrated that SBA-15@BDA NPs absorb selectively Pb2+ ions via chemisorption. The SBA-15@BDA NPs show Pb2+ ions with a maximum adsorption capacity of ~ 88% and an adsorbed quantity of approximately ~ 112 mg/g from the studied aqueous solution. The adsorption mechanism relies on coordination bonding between Pb2+ ions and surface-functionalized amine groups on SBA-15@BDA NPs. Furthermore, the proposed SBA-15@BDA NPs adsorbent demonstrated excellent reusability over five cycles without significantly reducing adsorption performance. As a consequence, SBA-15@BDA NPs might serve as an effective adsorbent for the selective removal of Pb2+ ions from aqueous effluent.

Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P=0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes (P=0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes (P=0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03542188.

Implications of CD45RA and CD45RO T cell subsets in patients of chronic rhinosinusitis with nasal polyposis infected with Aspergillus flavus.

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps. The study included 50 cases of CRSwNP and 50 healthy controls. Biopsies were subjected to KOH and culture for mycological investigation. We examined the changes in T helper (CD4+) and T cytotoxic (CD8+) in total T cells (CD3+) and expression of naive (CD45RA) and memory (CD45RO) cell markers in T cell subsets in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens in cases before and after treatment and in healthy controls by flow cytometry. Predominantly, A. flavus (86%) identified in nasal polyp biopsies of patients. An increased percentage of CD3+CD4+ T cells observed after A. flavus stimulation in patients when compared with healthy controls. The expression of CD4+CD45RA+ cells was significantly (P < .05) reduced in patients and increased CD4+CD45RO+ was observed upon stimulation with A. flavus in patients when compared with healthy control. Continuous exposure to inhaled fungal spores may induce aberrant immune responses to A. flavus spores, causing an allergic immunological reaction with high CD4+T cell responses, resulting in an unfavourable outcome. Elevated CD4+CD45RO+ T cells may transform the pathogenic response and highlight the chances of A. flavus reactive T cells involvement in prompting inflammation in CRSwNP.

Poliovirus surveillance in patients with primary immunodeficiencies, India.

Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future.

Certains individus qui présentent des immunodéficiences primaires et sont infectés par des poliovirus dérivés d'une souche vaccinale pourraient continuer à excréter le poliovirus pendant des mois sans que ce dernier ne soit détecté par le biais d'une surveillance de la paralysie flasque aiguë. Ces patients risquent donc de déclencher des épidémies de poliovirus qui mettent en péril les efforts visant à éradiquer la poliomyélite dans le monde. En vue d'identifier ces individus, nous avons élaboré un protocole d'étude pour établir, en Inde, un réseau de surveillance du poliovirus d'origine vaccinale lié à une immunodéficience. Au cours de la première étape, nous avons repéré des centres reconnus dans le pays, capables de diagnostiquer des patients atteints d'un syndrome d'immunodéficience primaire et de les recruter dans le cadre de l'étude. Le prélèvement des échantillons de selles auprès des sites participant à l'étude, la culture, l'isolement, la caractérisation des entérovirus et la communication des résultats à ces sites ont été pris en charge par le National Institute of Virology Mumbai Unit, conformément au protocole du Projet national de surveillance de la poliomyélite de l'OMS. Nous avons consacré la première phase de l'étude, qui s'est déroulée entre janvier 2020 et décembre 2021, à la mise en œuvre du protocole au sein de différents établissements médicaux sur sept sites participants, afin de déterminer le nombre d'infections au poliovirus chez les patients souffrant d'un syndrome d'immunodéficience primaire en Inde. Nous avons ensuite, durant la deuxième phase comprise entre janvier 2022 et décembre 2023, élargi l'étude en incluant 14 établissements supplémentaires à travers le pays. Nous sommes convaincus que ce protocole d'étude aidera d'autres pays à instaurer une surveillance du poliovirus dérivé d'une souche vaccinale et lié à une immunodéficience, qui leur servira à identifier et suivre les patients responsables d'une excrétion prolongée du poliovirus d'origine vaccinale. L'intégration, au sein du réseau existant dédié au poliovirus, d'une surveillance de ce type couplée à une surveillance de la paralysie flasque aiguë améliorera le dépistage systématique des patients atteints d'un syndrome d'immunodéficience primaire à l'avenir.

Las personas con inmunodeficiencias primarias infectadas por los poliovirus de origen vacunal pueden seguir excretando poliovirus durante meses sin que la vigilancia de la parálisis flácida aguda los detecte. Por lo tanto, estos pacientes suponen un riesgo de iniciar brotes de poliovirus que pongan en peligro los esfuerzos hacia la erradicación mundial de la poliomielitis. Para identificar a estas personas, diseñamos un protocolo de estudio para el establecimiento de una red de vigilancia de poliovirus de origen vacunal relacionados con inmunodeficiencias en la India. En el primer paso identificamos centros reconocidos en la India que pudieran diagnosticar e inscribir en el estudio a pacientes con trastorno de inmunodeficiencia primaria. La recogida de muestras de heces de los centros de estudio, el cultivo, el aislamiento, la caracterización de los enterovirus y la notificación a los centros de estudio se llevaron a cabo en el Instituto Nacional de Virología, Unidad de Mumbai, según el protocolo del Proyecto Nacional de Vigilancia de la Poliomielitis de la OMS. En la primera fase del estudio, de enero de 2020 a diciembre de 2021, aplicamos el protocolo en siete centros de estudio de diferentes institutos médicos para determinar la proporción de infecciones por poliovirus en pacientes con trastorno de inmunodeficiencia primaria de la India. A continuación, ampliamos el estudio con la inclusión de otros 14 institutos médicos de todo el país en la segunda fase, de enero de 2022 a diciembre de 2023. Creemos que este protocolo de estudio ayudará a otros países a iniciar la vigilancia de poliovirus de origen vacunal relacionados con la inmunodeficiencia para identificar y hacer un seguimiento de los pacientes que son excretores a largo plazo de poliovirus de origen vacunal. La integración de la vigilancia del poliovirus asociado a la inmunodeficiencia con la vigilancia de la parálisis flácida aguda de la red de poliovirus existente mejorará el cribado continuo de pacientes con trastorno por inmunodeficiencia primaria en el futuro.

Phytochemical profiling, anti-hyperglycemic, antifungal, and radicals scavenging potential of crude extracts of Athyrium asplenioides- an in-vitro approach.

This research was aimed to evaluate the phytochemical profile, antifungal, anti-hyperglycemic, as well as antioxidant activity competence of different extracts of Athyrium asplenioides through in-vitro approach. The A. asplenioides crude methanol extract contained considerable quantity of pharmaceutically precious phytochemicals (saponins, tannins, quinones, flavonoid, phenols, steroid, and terpenoids) than others (acetone, ethyl acetate, and chloroform). Interestingly, the crude methanol extract showed remarkable antifungal activity against Candida species (C. krusei: 19.3 ± 2 mm > C. tropicalis: 18.4 ± 1 mm > C. albicans: 16.5 ± 1 mm > C. parapsilosis: 15.5 ± 2 mm > C. glabrate: 13.5 ± 2 mm > C. auris: 7.6 ± 1 mm) at a concentration of 20 mg mL-1. The crude methanol extract also showed remarkable anti-hyperglycemic activity on concentration basis. Surprisingly, remarkable free radicals scavenging potential against DPPH (76.38%) and ABTS (76.28%) free radicals at a concentration of 20 mg mL-1. According to the findings, the A. asplenioides crude methanol extract contains pharmaceutically valuable phytochemicals and may be useful for drug discovery.

A study on the role of surface functional groups of metakaolin in the removal of methylene blue: Characterization, kinetics, modeling and RSM optimization.

In this study, thermally activated kaolinite clay is explored as a suitable material for dye removal applications, which gave rise to highly reactive silica species in a broad range of aluminosilicate clusters. Multinuclear NMR studies described it as a short-range network in which Al sites in IV, V, and VI are coordinated, and Si is present mainly as Si(Q4(1Al)). Critical parameters for methylene blue (MB) were determined by the Placket Burman Design (PBD) as initial dye concentration, contact time, adsorbent dosage, pH and size. The % of MB removal studied after optimizing the parameters by central composite design (CCD), based on Response Surface Methodology, was found to be 90%. The adsorption kinetics and thermodynamics were systematically studied and reported by fitting them into different models. The maximum removal of the dye reached 97.8 mg/g according to the Freundlich isotherm, accomplished through chemisorption, following a pseudo-second-order reaction and the process is thermodynamically spontaneous and endothermic. The line spectrum of X-ray photoelectron spectroscopy (XPS) shows the participation of Si, Al, O, Ca and Na of Metakaolin (AK) and nitrogen of MB in the adsorption process. The appropriate stabilization of the N atom of the chromophore on the Si and Al atom in AK resulting from the ionic interaction on the surface is established from an increase in the binding energy of Al and Si. A single bridging oxygen signal at 532.32eVcorresponding to AK after dye adsorption tends to form siloanol/aluminol, and their interaction is lowered to 531.58eV. Regeneration of adsorbent after thermal treatment without loss of efficiency proved.