MHC tetramer technology: Exploring T cell biology in health and disease.

Major histocompatibility complex (MHC) tetramers stand as formidable tools within T cell biology, facilitating the exploration and comprehension of immune responses. These artificial molecules, comprising four bound MHC molecules, typically with a specified peptide and a fluorescent label, play a pivotal role in characterizing T cell subsets, monitoring clonal expansion, and unraveling T cell dynamics during responses to infections or immunotherapies. Beyond their applications in T cell biology, MHC tetramers prove valuable in investigating a spectrum of diseases such as infectious diseases, autoimmune disorders, and cancers. Their instrumental role extends to vaccine research and development. Notably, when appropriately configured, tetramers transcend T cell biology research and find utility in exploring natural killer T cells and contributing to specific T cell clonal deletions.

Removal of arsenic from jarosite waste using hydrometallurgical treatment.

The jarosite waste used during this study consists of minute amount of arsenic that has a potential to be leached into environment when kept in open area. This study tried to recover arsenic from jarosite waste using hydrometallurgical treatment. The comprehensive characterization of jarosite samples was performed using various analytical techniques, including X-ray diffraction (XRD), Fourier transform Infrared (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX), and it was characterized as natrojarosite. For optimal removal of arsenic, the response surface methodology (RSM) was applied with the key factors, including dosage (A), time (B), temperature (C), and acid concentration (D) on the recovery of arsenic. The results indicated that the dosage (A) and acid concentration (D) demonstrated significant positive effects on arsenic recovery. As expected, the higher dosage and acid concentration was associated with increased recovery percentages for the arsenic from jarosite. Whereas time (B) and temperature (C) did not exhibit statistically significant recovery of arsenic within the specified experimental range. The contour plots showed the optimal operating conditions for the highest recovery percentage was approximately 52.61% when 2.5 g of jarosite was treated with 10 mol/L acid for 150 min at operating temperature of 80°. Although our study showed very moderate recovery of arsenic, it is first report where arsenic has been removed from jarosite waste. Readjustment of range of operating parameters would provide more insight into the further optimization of the yield.

Post kala-azar dermal leishmaniasis in the Indian sub-continent: challenges and strategies for elimination.

Visceral leishmaniasis (VL) is a severe and often fatal form of leishmaniasis caused by Leishmania donovani in the Indian sub-continent. Post Kala-azar Dermal Leishmaniasis (PKDL) is a late cutaneous manifestation of VL, typically occurring after apparent cure of VL, but sometimes even without a prior history of VL in India. PKDL serves as a significant yet neglected reservoir of infection and plays a crucial role in the transmission of the disease, posing a serious threat to the VL elimination program in the Indian sub-continent. Therefore, the eradication of PKDL should be a priority within the current VL elimination program aimed at achieving a goal of less than 1 case per 10,000 in the population at the district or sub-district levels of VL endemic areas. To accomplish this, a comprehensive understanding of the pathogenesis of PKDL is essential, as well as developing strategies for disease management. This review provides an overview of the current status of diagnosis and treatment options for PKDL, highlighting our current knowledge of the immune responses underlying disease development and progression. Additionally, the review discusses the impact of PKDL on elimination programs and propose strategies to overcome this challenge and achieve the goal of elimination. By addressing the diagnostic and therapeutic gaps, optimizing surveillance and control measures, and implementing effective intervention strategies, it is possible to mitigate the burden of PKDL and facilitate the successful elimination of VL in the Indian sub-continent.

Exploring antiviral potency of N-1 substituted pyrimidines against HIV-1 and other DNA/RNA viruses: Design, synthesis, characterization, ADMET analysis, docking, molecular dynamics and biological activity.

A novel series of pyrimidine derivatives, bearing modified benzimidazoles at N-1 position, has been designed, synthesized and screened as NNRTIs against HIV and as broad-spectrum antiviral agents. The molecules were screened against different HIV targets using molecular docking experiment. The docking results indicated that the molecules interacted well with the residues Lys101, Tyr181, Tyr188, Trp229, Phe227 and Tyr318 present in NNIBP of HIV-RT protein, formed quite stable complexes and, thus, behaved as probable NNRTIs. Among these compounds, 2b and 4b showed anti-HIV activity with IC50 values as 6.65 µg/mL (SI = 15.50) and 15.82 µg/mL (SI = 14.26), respectively. Similarly, compound 1a showed inhibitory property against coxsackie virus B4 and compound 3b against different viruses. Molecular dynamics simulation results unequivocally demonstrated the higher stability of the complex HIV-RT:2b than the HIV-RT:nevirapine complex. The MM/PBSA-based binding free energy (-) 114.92 kJ/mol of HIV-RT:2b complex in comparison to that of HIV-RT:nevirapine complex (-) 88.33 kJ/mol, further demonstrated the higher binding strength of 2b and thus, established the potential of compound 2b as a lead molecule as an HIV-RT inhibitor.

COVID-19: Pathophysiology, Transmission, and Drug Development for Therapeutic Treatment and Vaccination Strategies.

COVID-19, a dreaded and highly contagious pandemic, is flagrantly known for its rapid prevalence across the world. Till date, none of the treatments are distinctly accessible for this life-threatening disease. Under the prevailing conditions of a medical emergency, one creative strategy for the identification of novel and potential antiviral agents gaining momentum in research institutions and progressively being leveraged by pharmaceutical companies is target-based drug repositioning/repurposing. Continuous monitoring and recording of results offer anticipation that this strategy may help to reveal new medications for viral infections. This review recapitulates the neoteric illation of COVID-19, its genomic dispensation, molecular evolution via phylogenetic assessment, drug targets, the most frequently worldwide used repurposed drugs and their therapeutic applications, and a recent update on vaccine management strategies. The available data from solidarity trials exposed that the treatment with several known drugs, viz. lopinavir-ritonavir, chloroquine, hydroxychloroquine, etc. had displayed various antagonistic effects along with no impactful result in the diminution of mortality rate. The drugs, like remdesivir, favipiravir, and ribavirin, have proved to be quite safer therapeutic options for treatment against COVID-19. Similarly, dexamethasone, convalescent plasma therapy and oral administration of 2DG are expected to reduce the mortality rate of COVID-19 patients.

Multi-criteria decision making and Dempster-Shafer model-based delineation of groundwater prospect zones from a semi-arid environment.

The present study illustrates the delineation of the groundwater potential zones in one of the most critical and drought-affected areas under Bundelkhand region of Uttar Pradesh (India). Hydrological evaluations were carried out using GIS tools and remote sensing data which ultimately yielded several thematic maps, such as lineament density, land use/land cover, drainage density, lithology, slope, geomorphology, topographic wetness index (TWI), DEM, and soil. Thematic layers were assigned relative weightages as per their groundwater potential prospects under multi-criteria decision making (MCDM) method through analytical hierarchy process (AHP). To recognize the groundwater potential zone, weighted overlay analysis was also performed. Additionally, for testing of the Dempster-Shafer model, 16 wells in the study area have been selected. Based on the probability of the groundwater occurrence, the belief factor was equated to delineate groundwater potential zones which illustrate five different potential zones. According to the AHP model, the northwest side of the study area is characterized with very high potential zones whereas the northeast and southeast regions constitute medium and low groundwater potential zones respectively. According to the DS model, very high groundwater potential zones constitute 17% and the remaining area falls under low potential. Overall accuracy of the DS model is higher than AHP model.

Emerging role of γδ T cells in protozoan infection and their potential clinical application.

γδ T cells are thymus derived heterogeneous and unconventional T- lymphocyte expressing TCR γ (V γ9) and TCRδ (Vδ2) chain and play an important role in connecting innate and adaptive armaments of immune response. These cells can recognize wide ranges of antigens even without involvement of major histocompatibility complex and exert their biological functions by cytotoxicity or activating various types of immune cells. In recent past, γδ T cells have emerged as an important player during protozoa infection and rapidly expand after exposure with them. They have also been widely studied in vaccine induced immune response against many bacterial and protozoan infections with improved clinical outcome. In this review, we will discuss the various roles of γδ T cells in immunity against malaria and leishmaniasis, the two important protozoan diseases causing significant mortality and morbidity throughout the world.

Separation of pollutants from aqueous solution using nanoclay and its nanocomposites: A review.

Wastewater is always composed of different pollutants, most of which are toxic to the living being. It is very tough to separate all those diverse groups of contaminants using a single process or single material. Rather a sustainable and environment friendly processes should be adapted to restrict the secondary pollution generation. Nanoclay and its nanocomposites are one of the most used adsorbents that have been modified and used for the separation of almost all types of pollutants, including dyes, heavy metals, fluoride, nitrate, ammonia, emerging pollutants and bacteria. They are relatively inexpensive, easy to exploit and relatively maintenance-free. Thus, recent research bloomed for developing suitable adsorbents, including clay nanocomposites. The advantages and drawbacks of all the clay nanocomposites-based processes have been discussed critically in this article. Nano-clays or other nanoparticles incorporated synthetic and natural polymers-based clay nanocomposites were synthesized, and it was found that they can remove dyes in the range between 48 mg/g and 1994 mg/g. Similarly, they separate a diverse group of heavy metal ions, including As, Cu, Co, Pd, Zn, Cr, Ni, Cd, and Hg, in the range of 0.073-1667 mg/g. The clay nanocomposites also showed fluoride removal efficacy in the range of 0.134-23 mg/g. They are also useful for the separation of emerging pollutants like pesticides, pharmaceuticals, personal care products, trace elements, and particulate matters in the range of 0.1-651 mg/g the clay nanocomposites showed considerable nitrate, ammonia and bacteria removal efficacy too. Though it seems promising, more investigations with real wastewater and pilot-scale studies are recommended to explore large-scale wastewater treatment capabilities.

Alkylated benzimidazoles: Design, synthesis, docking, DFT analysis, ADMET property, molecular dynamics and activity against HIV and YFV.

A series of alkylated benzimidazole derivatives was synthesized and screened for their anti-HIV, anti-YFV, and broad-spectrum antiviral properties. The physicochemical parameters and drug-like properties of the compounds were assessed first, and then docking studies and MD simulations on HIV-RT allosteric sites were conducted to find the possible mode of their action. DFT analysis was also performed to confirm the nature of the hydrogen bonding interaction of active compounds. The in silico studies indicated that the molecules behaved like possible NNRTIs. The nature - polar or non-polar and position of the substituent present at fifth, sixth, and N-1 positions of the benzimidazole moiety played an important role in determining the antiviral properties of the compounds. Among the various compounds, 2-(5,6-dibromo-2-chloro-1H-benzimidazol-1-yl)ethan-1-ol (3a) showed anti-HIV activity with an appreciably low IC50 value as 0.386 × 10-5µM. Similarly, compound 2b, 3-(2-chloro-5-nitro-1H-benzimidazol-1-yl) propan-1-ol, showed excellent inhibitory property against the yellow fever virus (YFV) with EC50 value as 0.7824 × 10-2µM.