Despite clinical use of immunosuppressive agents, the immunopathogenesis of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remains unclear. Src homology 3-binding protein 2 (SH3BP2), a scaffold protein, forms an immune signaling complex (signalosome) with 17 other proteins, including phospholipase Cγ2 (PLCγ2) and Rho-guanine nucleotide exchange factor VAV2 (VAV2). Bioinformatic analysis of human glomerular transcriptome (Nephrotic Syndrome Study Network cohort) revealed upregulated SH3BP2 in MCD and FSGS. The SH3BP2 signalosome score and downstream MyD88, TRIF, and NFATc1 were significantly upregulated in MCD and FSGS. Immune pathway activation scores for Toll-like receptors, cytokine-cytokine receptor, and NOD-like receptors were increased in FSGS. Lower SH3BP2 signalosome score was associated with MCD, higher estimated glomerular filtration rate, and remission. Further work using Sh3bp2KI/KI transgenic mice with a gain-in-function mutation showed ~6-fold and ~25-fold increases in albuminuria at 4 and 12 weeks, respectively. Decreased serum albumin and unchanged serum creatinine were observed at 12 weeks. Sh3bp2KI/KI kidney morphology appeared normal except for increased mesangial cellularity and patchy foot process fusion without electron-dense deposits. SH3BP2 co-immunoprecipitated with PLCγ2 and VAV2 in human podocytes, underscoring the importance of SH3BP2 in immune activation. SH3BP2 and its binding partners may determine the immune activation pathways resulting in podocyte injury leading to loss of the glomerular filtration barrier.

The sluggish oxygen evolution reaction (OER) remains a major bottleneck in hydrogen generation through electrolysis, particularly at large current operations. Thus, there is a huge interest in the development of...

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

BN50/NiO50 and Au-loaded BN50/NiO50 nanocomposite films were separately fabricated on the glass substrates for carrier transport and photoconductivity properties. X-ray diffraction pattern of the films show the hexagonal structure of BN and presence of defect states by Nelson Riley factor analysis. Morphological images show spherical shaped particles with highly porous structure. The incorporation of NiO may hindered growth of BN layers and resulted in spherical particles. Temperature-dependent conductivity describes semiconductor transport behaviour for deposited nanocomposite films. Thermal activation conduction with low activation energy (∼0.308 eV) may be responsible for the resulting conductivity. Further, the light intensity dependent photoelectrical properties of BN50/NiO50 and Au-loaded BN50/NiO50 nanocomposites have been explored. The effect of Au nanoparticles loading on enhanced photo-conductivities (∼22% increase) than bare nanocomposite film has been elaborated by proposed mechanism. This study provided the insightful information for carrier transport and photoconductivity of BN-based nanocomposites.

Abstract In the current study, we report an excellent high temperature oxidation resistance of AlCoCrFeNi high entropy alloy (HEA) following surface modification. The surface properties of HEA were tailored through a severe surface deformation technique. The as cast HEA exhibited coarse grain B2/BCC microstructure. In contrast, processed specimen showed significant grain refinement along with B2/BCC to FCC phase-transition. The processed specimen demonstrated 11–67% reduction in the oxidation kinetics. Cr2O3 and Al2O3 were the predominant oxides formed in all the oxidized specimens. In addition, Cr, Fe and Co rich spinels were also found in the as cast oxidized specimens. The superior oxidation resistance of the processed specimen is attributed to the microstructural refinement resulting in the formation of protective dense chromia layer.

Boron Neutron Capture Therapy (BNCT) is a targeted radiotherapy modality in which 10B enriched compounds are delivered for local treatment of the cancer cells. In this work, boron carbon nitride (BCN) has been explored as a potential boron compound for BNCT. BCN compound with high solubility has been synthesized by simple solvothermal method. Structural analysis show synthesis of hexagonal BCN with presence of defect states. Morphological analysis show formation of layered structure with highly porous network. The optical properties have also been studied and calculated band gap of material is similar to 3.85 eV. Cytotoxicity analysis show that synthesized material is relatively less toxic and can be explored for BNCT applications. The anti-tumor effect on HeLa and U-87MG cell lines show potential of BCN in comparison to clinically studied L-BPA compound.

Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens. The mast cell's role as a cellular interface between external and internal environments as well as between vasculature and tissues is critical for protection and repair. Mast cell interactions with different immune and nonimmune cells through secreted inflammatory mediators may also turn in favor of disease promoting agents. First and forefront, mast cells are well recognized for their multifaceted functions in allergic diseases. Reciprocal communication between mast cells and endothelial cells in the presence of bacterial toxins in chronic/sub-clinical infections induce persistent vascular inflammation. We have shown that mast cell proteases and histamine induce endothelial inflammatory responses that are synergistically amplified by bacterial toxins. Mast cells have been shown to exacerbate vascular changes in normal states as well as in chronic or subclinical infections, particularly among cigarette smokers. Furthermore, a potential role of mast cells in SARS-CoV-2-induced dysfunction of the capillary-alveolar interface adds to the growing understanding of mast cells in viral infections. The interaction between mast cells and microglial cells in the brain further highlights their significance in neuroinflammation. This review highlights the significant role of mast cells as the interface that acts as sensor and early responder through interactions with cells in systemic organs and the nervous system.

Material processing is often performed to form a fine grain structure with uniform distribution of mechanical properties. In the present study, a one-step solid phase processing technique that take advantage of in-situ reactive metallurgy, called stationary friction processing (SFP), is proposed to improve high temperature oxidation performance of AlCoCrFeNi high entropy alloy (HEA). The strategy involves producing a multi-phase fine-grain microstructure through SFP. The processed specimen retarded the oxidation kinetics by ∼52%. The electrochemical impedance spectroscopy coupled with transmission electron microscopy provided new insights into the physico-chemical nature and performance of the oxide-scale. Processed specimen demonstrated an increase in the polarization resistance with the immersion time while unprocessed HEA showed the reverse trend. The excellent oxidation performance was attributed to thin, adherent and uniform oxide layer on the processed HEA.

In the last few decades, the spinel ferrite with general formula MFe2O4 (M: Co, Cu, Fe, Zn, Ni, etc.) has enlarged the enormous attention of the scientific community owing to their utilization in various potential applications. Therefore, it is essential to understand the existing physical processes in spinel ferrites in order to tailor-make these materials for modern technology. The ferrites, being inhomogeneous dielectric materials, consist of individual high-conducting grains separated by either air gaps or low-conducting layers. The study of their dielectric properties provides information regarding the behavior of localized charge carriers that helps in understanding the dielectric polarization mechanism. Due to high resistivity, low eddy current losses, and convincingly low costs, these materials are coupled with remarkable microwave applications such as circulators, isolators, and phase shifters. This chapter focuses on the dielectric properties of spinel ferrites nanostructures. Here, we discuss the details of the dielectric properties of spinel ferrites and the involved ongoing physical phenomena to customize these materials for technological applications.

Overactivated NLRP3 inflammasome has been shown to associate with an increasing number of disease conditions. Activation of the NLRP3 inflammasome results in caspase-1-catalyzed formation of active pro-inflammatory cytokines (IL-1β and IL-18) resulting in pyroptosis. The multi-protein composition of the NLRP3 inflammasome and its sensitivity to several damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) make this extensively studied inflammasome an attractive target to treat chronic conditions. However, none of the known NLRP3 inhibitors has been approved for clinical use. Sulfonylurea and covalent inhibitors with electrophilic warhead (Michael acceptor) are among the prominent classes of compounds explored for their NLRP3 inhibitory effects. Chalcone, a small molecule with α, β unsaturated carbonyl group (Michael acceptor), has also been studied as a promising scaffold for the development of NLRP3 inhibitors. Low molecular weight, easy to manipulate lipophilicity and cost-effectiveness have attracted many to use chalcone scaffold for drug development. In this review, we highlight chalcone derivatives with NLRP3 inflammasome inhibitory activities. Recent developments and potential new directions summarized here will, hopefully, serve as valuable perspectives for investigators including medicinal chemists and drug discovery researchers to utilize chalcone as a scaffold for developing novel NLRP3 inflammasome inhibitors.

Engineering materials are known to show trade-off between high tensile strength and ductility. The si-multaneous enhancement of strength and ductility can make them more appealing for various structural applications. In this study, we demonstrate a facile technique to address the conflicting strength-ductility trade-off in crystalline materials. AlCoCrFeNi high entropy alloy (HEA), one of the most popular multi -principal alloy system, was considered for the investigation. The as-cast AlCoCrFeNi alloy showed a coarse grain microstructure with BCC/B2 phase. The as-cast alloy was subjected to severe plastic deformation using a facile technique known as stationary friction processing (SFP). The SFP for only 15 min resulted in an order of magnitude reduction in the grain size along with BCC to FCC phase transformation. The processed sample demonstrated more than 2 times higher ultimate tensile strength (-650 MPa) compared to as-cast HEA (-310 MPa). Further, the ductility of the processed HEA was enhanced from 11 % to 18 %. The combination of fine grain structure along with BCC to FCC transition through SFP enabled exceptional mechanical prop-erties in the HEA. This approach can easily be extended to other alloy systems for designing high tensile strength and superior ductility.(c) 2022 Elsevier B.V. All rights reserved.

In the current study, the high temperature oxidation behavior of AlCoCrFeNi high entropy alloy (HEA) following severe shear deformation was investigated. X-ray diffraction and transmission electron micro-scopy analysis confirmed spinodal distribution of B2 and BCC phase in the as cast specimen. In contrast, the processed specimen showed a dual phase microstructure (B2/BCC+FCC) after shear deformation. Electron backscattered diffraction analysis revealed significant grain refinement from 90 mu m for the as-cast HEA to nearly 2 mu m for the processed specimen. The processed specimen showed up to 66% reduction in the oxidation kinetics compared to the as cast alloy. The remarkable improvement in the high-temperature oxidation performance following processing is attributed to complete microstructure refinement. The current study provides a sustainable solution and a new pathway for addressing the looming problem of material deterioration at high temperatures. (c) 2022 Elsevier B.V. All rights reserved.

Bimetallic AuAg (Au (80%) and Ag (20%)) nanoparticles (NPs) have been synthesized in fused quartz matrix using sequential ion implantation and post-annealing in air at 600 degrees C, 700 degrees C, 800 degrees C and 900 degrees C. X-ray diffraction (XRD) results confirm the formation of crystalline Au80Ag20 bimetallic NPs after annealing. Transmission electron microscopy (TEM) investigations have confirmed presence of spherical AuAg alloyed and few AuAg alloy core- Ag shell/satellite NPs. Rutherford backscattering spectra, along with fittings, revealed the mixing of Au and Ag atoms after annealing and movement of elements towards the surface. The peak position of the surface plasmon resonance (SPR) feature of Au has been shifted towards higher energy after sequential Ag implantation. The SPR peak position and intensity is further modified after annealing of Au80Ag20 NPs. The mechanism of modified SPR properties is mechanistically discussed by considering the diffusion, alloying, segregation and redistribution of Au/Ag in the host matrix.

The electrical properties of boron carbon nitride (BCN) were studied using a thin-film device of the material. Fourier transform infrared spectroscopy spectrum demonstrates the atomic intermixing of boron, carbon, and nitrogen in BCN film. Also, bonding configuration and linkage of carbon with more electronegative nitrogen atoms were observed. X-ray photoelectron spectroscopy analysis shows the dominance of graphitic carbon and h-BN domains in the deposited film. The photoluminescence studies of the deposited film show a broad emission in the ultraviolet and visible region due to band-to-band transition of BCN and defect states-induced emission, respectively. The deposited film shows the low dielectric constant value of 2.97 with the variation of temperature and frequency. Low-temperature studies show an increase in conductivity (obtained σ = 2.98 × 10–4 S/cm) from 223 to 273 K due to the dominance of BCN superlattice. In contrast, a reduction in conductivity is observed from 273 to 300 K with the increase in inter-grain boundary area and the ascendency of the boron nitride domain.