Impact of bridge heterology on functional parameters of ELISA for 17α-methyltestosterone.

In this study, we have developed bridge heterologous ELISA for the detection of 17α- Methyltestosterone by incorporating aromatic spacers between 17α-Methyltestosterone-3-Carboxymethyloxime and Horseradish peroxidase label through N-hydroxysuccinimide mediated carbodiimide reaction method. The immunogen 17α-Methyltestosterone-3-Carboxymethyloxime-Bovine serum albumin used to generate the antibody was also prepared by the N-hydroxysuccinimide mediated carbodiimide reaction without using any spacer. We have studied the impact of bridge/aromatic spacers on functional parameters i.e. sensitivity, affinity and ED50 of the bridge heterologous assay and compared it with homologous assay. The five combinations of bridge heterologous assay using 17α-Methyl testosterone-3-CMO-BSA antiserum and 17α-MT-3-CMO-4,4'-Diaminodiphenyl sulphide-HRP, 17α MT-3-CMO-4,4'-Oxydianiline-HRP, 17α-MT-3-CMO-Benzidine-HRP, 17α- MT-3-CMO-p-Phenylenediamine-HRP and 17α-MT-3-CMO-Dapson-HRP enzyme conjugates were evaluated. Out of these five combinations, the combination 17α-MT-3-CMO-BSA with 17α-MT-3-CMO-Benzidine-HRP showed the best results. Sensitivity, affinity and ED50 were improved and found to be 0.02 ng/mL, 0.086 × 10-8 L/mol and 2.95 ng/mL than homologous assay where Sensitivity, affinity and ED50 were 0.11 ng/mL, 0.02 × 10-8 L/mol and 5.78 ng/mL respectively. The cross-reactivity for this bridge heterologous assay combination was seen with only 4 steroids (6-hydrotestosterone- 6%, Testosterone-5.14%, Danazol-0.9% and Nandrolone-0.85%) instead of eight steroids (6-hydrotestosterone-43.75%, Testosterone-38.3%, Danazol-25.14%, Androstenediol-19.16%, Nandrolone-19%, Metandienone-5%, Androstenedione-3.52%, and 17α dimethyltestosterone-2%) as in homologous assay out of 59 structurally related steroids. Thus, the results of this study conclude that the incorporation of aromatic spacer (bridge) in enzyme conjugate has a crucial role in improving sensitivity, specificity, ED50 and affinity of the developed assay. The assay was then studied for parameters such as recovery (97.4%-108.6%), precision (Inter and Intra-assay coefficient of variation <10%), correlation coefficient (R2 = 0.96) by comparing with the commercial kit and validated by measuring levels of 17α- methyltestosterone in rat serum after administering them.

NFκB1 inhibits memory formation and supports effector function of ILC2s in memory-driven asthma.

Background: ILC2s are capable of generating memory. The mechanism of memory induction and memory-driven effector function (trained immunity) in ILC2s is unknown. Objective: NFκB1 is preferentially expressed at a high level in ILC2s. We examined the role of NFkB1 in memory induction and memory-driven effector function in a mouse model of asthma. Methods: Intranasal administration of Alternaria, flexivent, ELISA, histology, real-time PCR, western blot, flow cytometry and immunofluorescence staining. Results: NFκB1 was essential for the effector phase of memory-driven asthma. NFκB1 was critical for IL33 production, ILC2 generation, and production of type-2 cytokines, which resulted in eosinophilic inflammation and other features of asthma. NFκB1 induction of type-2 cytokines in ILC2s was independent of GATA3. NFκB1 was important for allergen induction of ILC3s and FoxP3+ Tregs. NFκB1 did not affect Th2 cells or their cytokine production. In contrast to its protagonistic role in the effector phase, NFκB1 had an antagonistic role in the memory phase. NFκB1 inhibited allergen-induced upregulation of memory-associated repressor and preparedness genes in ILC2s. NFκB1 upregulated RUNX1. NFκB1 formed a heterodimer with RUNX1 in ILC2s. Conclusions: NFκB1 positively regulated the effector phase but inhibited the induction phase of memory. The foregoing pointed to an interdependent antagonism between the memory induction and the memory effector processes. The NFκB1-RUNX1 heterodimer represented a non-canonical transcriptional activator of type-2 cytokines in ILC2s.

Role of epigenetics in innate lymphoid cells.

Epigenetics plays a crucial role in gene regulation and cell function without changing the DNA sequence. The process of differentiation in eukaryotes during cellular morphogenesis is a paradigm of epigenetic change; stem cells develop into pluripotent cell lines in the embryo, eventually becoming terminally developed cells. Recently, epigenetic changes were shown to play an important role in immune cell development, activation and differentiation, which impacts chromatin remodeling, DNA methylation, post-translational histone modifications and small or lncRNA engagement. Innate lymphoid cells (ILCs) are newly identified immune cells that lack antigen receptors. ILCs differentiate from hematopoietic stem cells via multipotent progenitor stages. In this editorial, the authors discuss the epigenetic regulation of ILC differentiation and function.

Introduction of Methyl Group in Substituted Isoselenazolones: Catalytic and Mechanistic Study.

Copper-catalyzed direct selenation of substituted 2-bromo-N-phenylbenzamide substrates with elemental selenium powder provided a series of methoxy-substituted isoselenazolones via the C-Se and Se-N bond formations. Phenolic substituted isoselenazolones have been obtained by O-demethylation of the corresponding methoxy-substituted analogues using boron tribromide. Some isoselenazolones have been structurally characterized by X-ray single-crystal analysis. The glutathione peroxidase (GPx)-like antioxidant activity of isoselenazolones has been evaluated both in thiophenol and coupled-reductase assays. All isoselenazolones showed good GPx-like activities in the coupled-reductase assay. The ferric-reducing antioxidant power of phenolic antioxidants has also been evaluated. The best phenolic antioxidants were found to be good ferric-reducing antioxidant power agents. The single electron transfer, hydrogen atom transfer, and proton-coupled electron transfer mechanisms for the antioxidant properties of all catalysts have been supported by density functional theory calculations. The catalytic cycle was proposed for one of the phenolic isoselenazolones involving diselenide, selenenyl sulfide, selenol, and selenenic acid as intermediates using 77Se{1H} NMR spectroscopy.

Fabrication of vertically aligned CNT- vanadium oxide hybrid architecture with enhanced compressibility and supercapacitor performance.

The demand for energy storage devices in wearable electronics effectuates a requisition for compressible and flexible supercapacitors with high performance and mechanical reliability. We report the fabrication of vanadium oxide hybrid with VACNT and its electrochemical supercapacitor performance along with the compression response. Compressive modulus of 730 ± 40 kPa is obtained for bare VACNT forest whereas its hybrid with vanadium oxide shows a compressive modulus of 240 ± 60 kPa. Controlled CVD process enabled the formation of porous CNT architecture coated with vanadium oxide particles due to the simultaneous reduction of V2O5and partial oxidation of CNT forest. Vanadium oxide decorated on vertically aligned carbon nanotubes acts as the active material for supercapacitor applications. A 17 folds increase in areal capacitance and 36 folds increase in volumetric capacitance are observed on depositing vanadium oxide particles on the VACNT forest. High coulombic efficiency of 97.8% is attained even after 10 000 charge-discharge cycles indicating the high stability of the hybrid.

Stem Cell Therapy and Innate Lymphoid Cells.

Innate lymphoid cells have the capability to communicate with other immune cell types to coordinate the immune system functioning during homeostasis and inflammation. However, these cells behave differently at the functional level, unlike T cells, these cells do not need antigen receptors for activation because they are activated by the interaction of their receptor ligation. In hematopoietic stem cell transplantation (HSCT), T cells and NK cells have been extensively studied but very few studies are available on ILCs. In this review, an attempt has been made to provide current information related to NK and ILCs cell-based stem cell therapies and role of the stem cells in the regulation of ILCs as well. Also, the latest information on the differentiation of NK cells and ILCs from CD34+ hematopoietic stem cells is covered in the article.

Interplay between Thermal Stress and Interface Binding on Fracture of WS2 Monolayer with Triangular Voids.

The defect engineering of two-dimensional (2D) materials has become a pivotal strategy for tuning the electrical and optical properties of the material. However, the reliable application of these atomically thin materials in practical devices require careful control of structural defects to avoid premature failure. Herein, a systematic investigation is presented to delineate the complex interactions among structural defects, the role of thermal mismatch between WS2 monolayer and different substrates, and their consequent effect on the fracture behavior of the monolayer. Detailed microscopic and Raman/PL spectroscopic observations enabled a direct correlation between thermal mismatch stress and crack patterns originating from the corner of faceted voids in the WS2 monolayer. Aberration-corrected STEM-HAADF imaging reveals the tensile strain localization around the faceted void corners. Density functional theory (DFT) simulations on interfacial interaction between the substrate (Silicon and sapphire -Al2O3) and monolayer WS2 revealed a binding energy between WS2 and Si substrate is 20 times higher than that with a sapphire substrate. This increased interfacial interaction in WS2 and substrate-aided thermal mismatch stress arising due to difference in thermal expansion coefficient to a maximum extent leading to fracture in monolayer WS2. Finite element simulations revealed the stress distribution near the void in the WS2 monolayer, where the maximum stress was concentrated at the void tip.

Role of type-2 innate lymphoid cells (ILC2s) in type-2 asthma.

PURPOSE OF REVIEW: The purpose of this review is to provide a synthesis of recent discoveries about type-2 innate lymphoid cells, especially, as they relate to the pathogenesis of asthma. RECENT FINDINGS: We focused on features and characteristics of type-2 innate lymphoid cells (ILC2s) that distinguish them from other type-2 cells, especially Th2 cells. We collected and reviewed data related to human asthma and airway ILC2s. We examined the concept of ILC2 memory and trained immunity. We also analyzed steroid resistance of ILC2s, which is relevant for steroid-resistant asthma. SUMMARY: The implications of the findings include an understanding of ILC2 inflammation, and pathways and molecules that can be targeted by biologics and other therapeutic agents for management severe and steroid-resistant asthma.

Content analysis of educational videos on hand hygiene during COVID-19 pandemic.

BACKGROUND: Online platforms are the most popular mode of entertainment, simultaneously imparting knowledge and education. During COVID pandemic, there was a sudden influx of educational videos on social media/websites with a purpose of spreading the information about hand hygiene (HH) practices. The aim of this study was to explore and assess the HH videos based on its content and technical quality to promote the learning experience of videos. MATERIALS AND METHODS: HH videos from the official sites of five international health organizations and 42 national health institutes were assessed based on their availability of the HH videos. Verified YouTube videos on HH since January 2020 were further screened and assessed using the author's designed validated checklist. Each video was systematically evaluated and scored against the seven categories, namely introduction, audio, visuals/background, speaker/demonstrator, content, timing, and appeal. RESULTS: A total of 50 videos were assessed for analysis. Of these, 82% of videos scored >50%, i.e., 14. Among low scorer, seven videos were from YouTube channel. Majority of the videos were technically sound, 44% aroused interest, 82% had a simple, understandable message; in around 46% of the videos, the presenter was a healthcare worker; and in 24%, the information was accurate as per the World Health Organization guidelines. CONCLUSIONS: This study concluded that most of the HH videos were found to be just above average in their content quality and technicality.

The molecular and epigenetic mechanisms of innate lymphoid cell (ILC) memory and its relevance for asthma.

Repetitive exposure of Rag1-/- mice to the Alternaria allergen extract generated a form of memory that elicited an asthma-like response upon a subthreshold recall challenge 3-15 wk later. This memory was associated with lung ICOS+ST2+ ILC2s. Genetic, pharmacologic, and antibody-mediated inhibition and adoptive transfer established an essential role for ILC2s in memory-driven asthma. ATAC-seq demonstrated a distinct epigenetic landscape of memory ILC2s and identified Bach2 and AP1 (JunD and Fosl2) motifs as major drivers of altered gene accessibility. scRNA-seq, gene knockout, and signaling studies suggest that repetitive allergenic stress induces a gene repression program involving Nr4a2, Zeb1, Bach2, and JunD and a preparedness program involving Fhl2, FosB, Stat6, Srebf2, and MPP7 in memory ILC2s. A mutually regulated balance between these two programs establishes and maintains memory. The preparedness program (e.g., Fhl2) can be activated with a subthreshold cognate stimulation, which down-regulates repressors and activates effector pathways to elicit the memory-driven phenotype.

Meta-analysis comparing valve-in-valve TAVR and redo-SAVR in patients with degenerated bioprosthetic aortic valve.

INTRODUCTION: The comparative efficacy and safety of valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) and redo-surgical AVR (redo-SAVR) in patients with degenerated bioprosthetic aortic valves remain unknown. METHOD: Digital databases were searched to identify relevant articles. Unadjusted odds ratios for dichotomous outcomes were calculated using a random effect model. A total of 11 studies comprising 8326 patients (ViV-TAVR = 4083 and redo-SAVR = 4243) were included. RESULTS: The mean age of patients undergoing ViV-TAVR was older, 76 years compared to 73 years for those undergoing SAVR. The baseline characteristics for patients in ViV-TAVR vs. redo-SAVR groups were comparable. At 30-days, the odds of all-cause mortality (OR 0.45, 95% CI 0.30-0.68, p = .0002), cardiovascular mortality (OR 0.44, 95% CI 0.26-0.73, p = .001) and major bleeding (OR 0.29, 95% CI 0.15-0.54, p = .0001) were significantly lower in patients undergoing ViV-TAVR compared to redo-SAVR. There were no significant differences in the odds of cerebrovascular accidents (OR 0.91, 95% CI 0.52-1.58, p = .74), myocardial infarction (OR 0.92, 95% CI 0.44-1.92, p = .83) and permanent pacemaker implantation (PPM) (OR 0.54, 95% CI 0.27-1.07, p = .08) between the two groups. During mid to long-term follow up (6-months to 5-years), there were no significant differences between ViV-TAVR and redo-SAVR for all-cause mortality, cardiovascular mortality and stroke. ViV-TAVR was, however, associated with higher risk of prosthesis-patient mismatch and greater transvalvular pressure gradient post-implantation. CONCLUSION: ViV-TAVR compared to redo-SAVR appears to be associated with significant improvement in short term mortality and major bleeding. For mid to long-term follow up, the outcomes were similar for both groups.

Effect of mHealth Interventions on Glycemic Control and HbA1c Improvement among Type II Diabetes Patients in Asian Population: A Systematic Review and Meta-Analysis.

Introduction: Due to the high prevalence of diabetes mellitus, it is pertinent to educate and inform diabetes patients about their self-management. It can be done effectively using innovative methods like mobile health (mHealth), which includes mobile applications, phone calls, and text messages. Thus, this meta-analysis was conducted to summarize the effectiveness of mHealth interventions for the management of diabetes compared with usual care in the Asian population. Materials and Methods: Searches were performed in electronic databases, namely PubMed, Scopus, Embase, and Cochrane Library, in August and September 2020. Search terms used were "Diabetes Mellitus," "mHealth," "glycemic control", "HbA1c levels," and "Blood glucose levels." The primary outcome was glycated hemoglobin and blood glucose levels. Trials were pooled, and heterogeneity was quantified using the I2 statistic. Results: The search yielded 3980 abstracts, of which 18 trials met the inclusion criteria. Lowering of Hba1c levels was reported in the majority of trials, which aided in Glycemic control. For post prandial blood glucose (PPBG) levels, a statistically significant reduction of value -20.13 (95%CI -35.16 to -5.10, P = 0.009, I2 = 59%) was seen in the mean in the intervention group, whereas for HbA1c levels the mean reduction in the intervention group was -0.44 (95%CI, -0.79 to 0.10, P = 0.01, I2 = 87%). Although these interventions proved beneficial for these outcomes, there was a difference in the amount of effects caused by different mHealth interventions. Conclusion: This study acknowledged the effects of different mHealth interventions as per their accessibility and availability in recent years. There is a need to include more studies in future reviews to generate a larger body of evidence for the reported outcomes. The researchers should give the utmost priority to the transparency while reporting the interventions for effective interpretation of the retrieved data.

Ultralow Thermal Conductivity and Large Figure of Merit in Low-Cost and Nontoxic Core-Shell Cu@Cu2O Nanocomposites.

Identification of novel materials with enhanced thermoelectric (TE) performance is critical for advancing TE research. In this direction, this is the first report on TE properties of low-cost, nontoxic, and abundant core-shell Cu@Cu2O nanocomposites synthesized using a facile and cheap solution-phase method. They show ultralow thermal conductivity of nearly 10-3 of the copper bulk value, large thermopower of ∼373 µVK-1, and, consequently, a TE figure of merit of 0.16 at 320 K which is larger than those of many of the potential TE materials such as PbTe, SnSe, and SiGe, showing its potential for TE applications. The ultralow thermal conductivity is mainly attributed to the multiscale phonon scattering from intrinsic defects in Cu2O, grain boundaries, lattice-mismatched interface, as well as dissimilar vibrational properties. The large thermopower is associated with a sharp modulation in carrier density of states due to charge transfer between Cu and Cu2O nanoparticles and carrier energy filtering. They are tuned by varying the trioctylphosphine concentration.

Influence of surfactant, particle size and dispersion medium on surface plasmon resonance of silver nanoparticles.

Clear influence of particle size, surfactants and dispersion medium on surface plasmon resonance (SPR) features of Ag nanoparticles (NPs), synthesized in thermal decomposition method, in the broad range of ultraviolet (UV) radiation, critical for many potential applications such as a photocatalyst, UV-sensor and detector, has been demonstrated here. It involves adsorbate coverage, interparticle distance or agglomeration, surface charge density and solvent refractive index (µ). NP agglomeration and surface charge density in solvents of varying µ have been studied systematically through zeta-potential (ζ) and hydrodynamic diameter (HD) using dynamic light scattering (DLS). The main SPR feature found at 316 nm in 31.5 nm NPs shifts to 320 nm in 15.1 nm NPs. The peak at 320 nm in air shifts to 259, 261 and 277 nm in polar solvent methanol, deionized water and ethanol, respectively and to 255, 275 and 282 nm in non-polar solvent n-hexane, benzene and toluene, respectively. In general, the decrease in particle size and increase in µ of solvents show red-shift. Curiously, a number of peaks up to seven in these solvents that are attributed to charge-transfer mechanism and change in inter-particle interaction of the NPs turning from a single peak of SPR in air has been observed for the first time. A model for re-adjustment of Fermi level (E F) of Ag NP and the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) to explain them has also been used. Moreover, the Drude model for shift in the position of SPR in these NPs is only applicable in non-polar solvents, not in polar solvents. Such novel features will be potential candidates for various applications.

Adventitial Cystic Disease of the Popliteal Artery Contributing to Supera Stent Fracture.

A 60-year-old male presented with complaints of a non-healing wound on his right shin. Initial angiography showed a 100% occlusion of the right superficial femoral artery thought to be thrombotic in nature; he was treated with percutaneous transluminal angioplasty and stenting. Three weeks later, he presented with continuing symptoms of claudication. Angiography revealed stent fracture. Careful review of his prior angiogram was consistent with adventitial cystic disease of the popliteal artery as the cause of the popliteal artery occlusion. He was then referred for femoral-popliteal bypass.