Novel genetic association of the Furin gene polymorphism rs1981458 with COVID-19 severity among Indian populations.

SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, it enters the host cell by activating the ACE2 receptor with the help of two proteasesi.e., Furin and TMPRSS2. Therefore, variations in these genes may account for differential susceptibility and severity between populations. Previous studies have shown that the role of ACE2 and TMPRSS2 gene variants in understanding COVID-19 susceptibility among Indian populations. Nevertheless, a knowledge gap exists concerning the COVID-19 susceptibility of Furin gene variants among diverse South Asian ethnic groups. Investigating the role of Furin gene variants and their global phylogeographic structure is essential to comprehensively understanding COVID-19 susceptibility in these populations. We have used 450 samples from diverse Indian states and performed linear regression to analyse the Furin gene variant's with COVID-19 Case Fatality Rate (CFR) that could be epidemiologically associated with disease severity outcomes. Associated genetic variants were further evaluated for their expression and regulatory potential through various Insilco analyses. Additionally, we examined the Furin gene using next-generation sequencing (NGS) data from 393 diverse global samples, with a particular emphasis on South Asia, to investigate its Phylogeographic structure among diverse world populations. We found a significant positive association for the SNP rs1981458 with COVID-19 CFR (p < 0.05) among diverse Indian populations at different timelines of the first and second waves. Further, QTL and other regulatory analyses showed various significant associations for positive regulatory roles of rs1981458 and Furin gene, mainly in Immune cells and virus infection process, highlighting their role in host immunity and viral assembly and processing. The Furin protein-protein interaction suggested that COVID-19 may contribute to Pulmonary arterial hypertension via a typical inflammation mechanism. The phylogeographic architecture of the Furin gene demonstrated a closer genetic affinity of South Asia with West Eurasian populations. Therefore, it is worth proposing that for the Furin gene, the COVID-19 susceptibility of South Asians will be more similar to the West Eurasian population. Our previous studies on the ACE2 and TMPRSS2 genes showed genetic affinity of South Asian with East Eurasians and West Eurasians, respectively. Therefore, with the collective information from these three important genes (ACE2, TMPRSS2 and Furin) we modelled COVID-19 susceptibilityof South Asia in between these two major ancestries with an inclination towards West Eurasia. In conclusion, this study, for the first time, concluded the role of rs1981458 in COVID-19 severity among the Indian population and outlined its regulatory potential.This study also highlights that the genetic structure for COVID-19 susceptibilityof South Asia is distinct, however, inclined to the West Eurasian population. We believe this insight may be utilised as a genetic biomarker to identify vulnerable populations, which might be directly relevant for developing policies and allocating resources more effectively during an epidemic.

Emergence of per- and poly-fluoroalkyl substances (PFAS) and advances in the remediation strategies.

A group of fluorinated organic molecules known as per- and poly-fluoroalkyl substances (PFAS) have been commonly produced and circulated in the environment. PFAS, owing to multiple strong CF bonds, exhibit exceptional stability and possess a high level of resistance against biological or chemical degradation. Recently, PFAS have been identified to cause numerous hazardous effects on the biotic ecosystem. As a result, extensive efforts have been made in recent years to develop effective methods to remove PFAS. Adsorption, filtration, heat treatment, chemical oxidation/reduction, and soil washing are a few of the physicochemical techniques that have shown their ability to remove PFAS from contaminated matrixes. However these methods also carry significant drawbacks, including the fact that they are expensive, energy-intensive, unsuitable for in-situ treatment, and requirement to be carried under dormant conditions. The metabolic products released upon PFAS degradation are largely unknown, despite the fact that thermal disintegration methods are widely used. In contrast to physical and chemical methods, biological degradation of PFAS has been regarded as efficient method. However, PFAS are difficult to instantly and completely metabolize through biological methods due to the limitations of biocatalytic mechanisms. Nevertheless, cost, easy-to-operate and environmentally safe are some of the advantages over its counterpart. The present review comprehensively discusses the occurrence of PFAS, the state-of-the science of remediation technologies and approaches applied, and the remediation challenges. The article also focuses on the future research directions toward the development of effective methods for PFAS-contaminated site in-situ treatment.

Hybrid approach combining deep learning and a rule based expert system for concept extraction from prescriptions.

Concept extraction from prescriptions is a very important task that provides a foundation for many of the downstream healthcare applications in decision making across the areas of pharmacovigilance, medication adherence, inventory management, and other matters of value-based care. Although short, these directions can sometimes be complex. With the increase in complexity of direction, it becomes harder to extract various concepts by only rule based expert system. It identifies major concepts like frequency, dosage, duration, etc. from the natural text direction using a combination of rules and deep learning (DL) based methods on a large real world data of a pharmacy chain. The DL module includes a fine-tuned BERT transformer and Gram CNN (Convolutional Neural Network) based NER (Named Entity Recognition) architecture. The proposed method utilizes the domain heuristics along with intelligent labelling and bootstrapping to help DL models extract concepts with high evaluation scores and thus provides a way for carrying out concept extraction using targeted methods instead of one single method. To the best of our knowledge, this is the best performance reported in the literature for concept extraction from doctor's prescription.

Studying C-reactive protein and D-dimer levels in blood may prevent severe complications: A study in Bangladeshi COVID-19 patients.

The ongoing COVID-19 pandemic has been a scientific, medical and social challenge. Since clinical course of this disease is largely unpredictable and can develop rapidly causing severe complications, it is important to identify laboratory biomarkers, which may help to classify patient's severity during initial stage. Previous studies have suggested C-reactive protein (inflammatory) and D-dimer (biochemical) as an effective biomarker. The differential severity in patients across the world and our limited understanding in the progression of the disease calls for a multi-country analysis for biomarkers. Therefore, we have analyzed these biomarkers among 228 Bangladeshi COVID-19 patients. We observed significant association of COVID-19 severity with these two biomarkers. Thus, we suggest to use these biomarkers for Bangladeshi COVID-19 patients for better disease monitoring. Such validated preventive measures may decrease the case fatality ratio substantially.

Vaccine hesitancy for coronavirus SARS-CoV-2 in Varanasi India.

With the rollout of the world's largest vaccine drive for SARS-CoV-2 by the Government of India on January 16 2021, India had targeted to vaccinate its entire population by the end of 2021. Struggling with vaccine procurement and production earlier, India overcome these hurdles, but the Indian population still did not seem to be mobilizing swiftly toward vaccination centers. The severe second wave has slowed the vaccination pace and was also one of the major contributing factors to vaccine hesitancy. To understand the nature of vaccine hesitancy and its underlying factors, we conducted extensive online and offline surveys in Varanasi and adjoining regions using structured questions. Most respondents were students (0.633). However, respondents from other occupations, such as government officials (0.10), have also participated in the study. Interestingly, most people (0.75) relied on fake news and did not take COVID-19 seriously. Most importantly, we noticed that a substantial proportion of respondents (relative frequency 0.151; mean age 24.8 years) reported that they were still not interested in vaccination. We observed a significant association between vaccine hesitancy and socioeconomic status (χ2 = 307.6, p < 0.001). However, we failed to detect any association between vaccine hesitancy and gender (χ2 = 0.007, p > 0.5). People who have neither been vaccinated nor have ever been infected may become the medium for spreading the virus and creating new variants, which may lead to the vaccine-resistant variant. We expect this extensive survey to help the Government upgrade their vaccination policies for COVID-19 in North India.

Magic Shotgun Nature with Scattergun Approach of Curcumin Repurposing in Obsessive-compulsive Disorder: A Novel Metaphysician of Drug Discovery.

BACKGROUND: Obsessive-Compulsive Disorder (OCD) is an intricate, debilitating neuropsychiatric disorder. Exclusively, Selective Serotonin Reuptake Inhibitors (SSRIs) are effective agents used for the treatment of OCD. However, SSRIs are not a magic pill-they do not respond adequately to everybody. In this consideration, a single drug target (magic bullet) is only a slightly superior option for all patients with a lot of pathognomonic signs. OBJECTIVE: The principal aim of the current study was to check the potential contribution of repurposing of magic shotgun nature of curcumin (rhizomes of Curcuma longa) with scattergun approach- proceeding a pioneer 'fine-tune' for obsessive-compulsive disorder. METHOD: Swiss albino mice (male 20 to 25 gram) were grouped into different groups (n = 6) used for the MBB (marble-burying behaviour) and MA (motor activity) test as a model for evaluation of anti-compulsive activity (Anti-OCD). Ethanolic extract of Curcuma longa (EECL-10, 15, 25, 40 mg/kg), or SSRI (fluoxetine 5, 10, 15 mg/kg) followed by pre-treated with either sub effective dose of fluoxetine attenuated MBB without effected the MA, or neurotoxin p-chlorophenyl alanine induced compulsive behavior and specific 5-HT receptors agonists/ antagonist, intraperitoneally revealed neuromodulation. RESULTS: EECL (40 mg/kg) significantly attenuated the MBB. Although, during treatments, none of the above had any critical impact on MA. p < 0.05 was considered significant in every case. CONCLUSION: Multiple drug-target interactions with multifarious biogenic receptors, supervene unexpected side effects followed by the repurposing of wanted effects (scattergun effect) were evoked by curcumin treatment. Finally, the study shows that EECL (curcumin) has anti-compulsive activity, which is mediated by neuromodulation with 5-HT receptors.

AS101-Loaded PLGA-PEG Nanoparticles for Autoimmune Regulation and Chemosensitization.

The in vivo delivery of therapeutic nanoparticles (NPs) represents a potentially powerful tool that can significantly alter the biological effects of pharmaceutically active compounds. Here, we report on sensitization of tumors to chemotherapy by ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) encapsulated in NPs, termed AS101-NPs, developed as a composite with the biocompatible and biodegradable copolymer of poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG). AS101 is a potent immunomodulating agent (both in vitro and in vivo) currently undergoing phase II clinical trials for antitumor activity and sensitization of tumors to chemotherapy. Approaches that can control the pharmacokinetic parameters to regulate its clearance from the administered drug delivery system and minimize side effects are of prodigious importance. A strategy to synthesize AS101-NPs by nanoprecipitation is presented, along with their physical characterization. The influence of AS101 encapsulation on its properties was evaluated in vivo. The AS101-NPs demonstrated a significantly enhanced peritoneal macrophage count compared with AS101 administered in vivo at a conventional dosage in mouse models. Moreover, AS101 inhibited B16 melanoma lung metastasis in mice when given intraperitoneally, before or after tumor cell inoculation. A bell-shaped dose-response was observed. The frequency of AS101 administration appears to be an important factor for achieving an optimal antimetastatic effect.

Selective production of furfural from the dehydration of xylose using Zn doped CuO catalyst.

Furfural is a versatile biomass-derived platform compound used for the synthesis of several strategic chemicals. The sonochemically synthesized Zn doped CuO nanoparticles (NPs) were used for the production of furfural. The catalytic activity of the Zn doped CuO NPs was examined, as a model, during the dehydration reaction of xylose to furfural. In addition to that, we have also compared the catalytic activity of the Zn doped CuO NP with ZnO NPs, ZnO bulk, CuO NPs, CuO bulk, etc. This nanoscale catalyst (Zn doped CuO NP) has a large surface area, which enhances its catalytic activity and enables it to completely convert the xylose to furfural at 150 °C within 12 h without any trace of by-products, as confirmed by HPLC, 13C NMR and 1H NMR. HPLC analysis demonstrated that the yield of furfural is up to 86 mol %, compared to the 45 mol % obtained with ZnO NPs, ZnO bulk, CuO NPs, CuO bulk, etc. as catalysts.

Hydroxyapatite coating on stainless steel pre-coated with bovine serum albumin at ambient conditions.

A biomimetic process for coating of nanosized hydroxyapatite on stainless steel, which capitalises the dual nature of the protein bovine serum albumin in both metal binding and a strong affinity for calcium ions, has been developed. The novelty of the process lies in pre-conditioning the metallic surface using the above protein prior to its mineralization with hydroxyapatite at ambient conditions. The microporous morphology of these coatings may provide favourable solubility and resorbability as desired by many orthopaedic and orthodontic applications.

Surfactant-free synthesis of a water-soluble PEGylated nanographeneoxide/metal-oxide nanocomposite as engineered antimicrobial weaponry.

A global upsurge in antibiotic resistance has led to research in metal-based antimicrobial therapy. Nonetheless, the clinical translation of metal oxides is often hampered by their poor aqueous solubility. This work unravels the surfactant-free synthesis of a water-soluble PEGylated nanographene oxide/zinc-doped copper oxide complex (NGO-PEG-Zn-CuO) with superior antibacterial activity. We uncover its mechanism of bacterial cell death over E. coli and S. aureus associated with oxidative stress and high production of reactive oxygen species (ROS) compared to NGO-ZnCuO, ZnCuO and NGO-PEG. A simple, one-step sonochemical technique is employed to deposit the Zn-CuO nanoparticles (NPs) on NGO-PEG. This complex demonstrates excellent aqueous solubility in different physiological solutions, including serum. Moreover, it exhibits excellent stability in water for a period of more than two months with almost no cytotoxicity effect on HeLa cells. Taken together, these results display the superior potency of the NGO-PEG-ZnCuO complex as a soluble and non-toxic compound with enhanced antibacterial properties.

New life for an old antibiotic.

Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we present, for the first time, the formation and deposition of stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/tetracycline (GO/TET) composite shows enhanced activity against both sensitive and resistant Staphylococcus aureus (S. aureus). The size and deposition of tetracycline (TET) nanoparticles on GO can be controlled by varying the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover, ultrasonic irradiation does not cause any structural and chemical changes to the TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The virtue of π-π stacking between GO and TET additionally facilitate the coating of TET NPs upon GO. A time dependent release kinetics of TET NPs from the GO surface is also monitored providing important insights regarding the mechanism of antibacterial activity of GO/TET composites. Our results show that the GO/TET composite is bactericidal in nature, resulting in similar values of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This composite is found to be active against TET resistant S. aureus at a concentration four times lower than the pristine TET. The sensitive S. aureus follows the same trend showing six times lower MIC values compared to pristine TET. GO shows no activity against both sensitive and resistant S. aureus even at a concentration as high as 1 mg/mL but influences the biocidal activity of the GO/TET composite. We propose that the unique structure and composition manifested by GO/TET composites may be further utilized for different formulations of antibiotics with GO. The sonochemical method used in this work can be precisely tailored for the stable deposition of a variety of antibiotics on the GO surface to reduce health risks and increase the spectrum of applications.