Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe.

The coronavirus disease-19 has left a permanent mark on the history of the human race. Severe acute respiratory syndrome coronavirus-2 is a positive-sense single-stranded RNA virus, first reported in Wuhan, China, in December 2019 and from there took over the world. Being highly susceptible to mutations, the virus's numerous variants started to appear, and some were more lethal and infectious than the parent. The effectiveness of the vaccine is also affected severely against the new variant. In this study, the infectious mechanism of the coronavirus is explained with a focus on different variants and their respective mutations, which play a critical role in the increased transmissibility, infectivity, and immune escape of the virus. As India has already faced the second wave of the pandemic, the future outlook on the likeliness of a third wave with respect to the Indian variants such as kappa, delta, and Delta Plus is also discussed. This review article aims to reflect the catastrophe of the variants of SARS-CoV-2 and the possibility of developing even more severe variants in the near future.

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria.

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.

Polyneuropathy in Critically Ill Mechanically Ventilated Children: Experience From a Tertiary Care Hospital in North India.

OBJECTIVES: To determine the prevalence of critical illness polyneuropathy and its risk factors in critically ill children mechanically ventilated for 7 days or more. DESIGN: Observational cohort study. SETTING: PICU of a tertiary care hospital from North India. PATIENTS: Children 1-15 years old admitted in PICU from June 2016 to September 2017, mechanically ventilated for 7 days or more, excluding those with diagnosed neuromuscular disease, stroke, or spinal pathology. INTERVENTION: Demographic details, diagnosis, treatment details, and anthropometry at admission and enrolment were recorded. Nerve conduction studies were performed after enrolment and repeated a week later, if the child was still in PICU. Medical Research Council scoring for muscle strength was performed in survivors. Risk factors including Pediatric Index of Mortality-2 score, sepsis, multiple organ dysfunction, hypoalbuminemia, use of steroids, neuromuscular-blocking agents, and vasopressors were recorded. Samples for the level of micronutrients (copper, zinc, folate, and vitamin B12) were collected at the time of enrolling the child and at the time of discharge. MEASUREMENTS AND MAIN RESULTS: Thirty-two children were enrolled, of whom 29 had features of critical illness polyneuropathy on evaluation at day 8 of mechanical ventilation (prevalence, 90.6% [95% CI, 80.5-100%]). The polyneuropathy was axonal in 26 (81.2%), mixed in one patient (3.1%), and uncharacterized in two (6.2%). Sepsis and multiple organ dysfunction were present in 31 subjects (96.9%). No risk factors for critical illness polyneuropathy could be identified although the study was not sufficiently powered to do so. The difference between serum micronutrient levels (copper, zinc, folate, and vitamin B12) between patients who developed polyneuropathy, and those who did not, was statistically insignificant. CONCLUSIONS: We observed a high prevalence of critical illness polyneuropathy in children in PICU, mechanically ventilated for 7 days or more; almost all of whom had underlying sepsis.

Production, optimization, scale up and characterization of polyhydoxyalkanoates copolymers utilizing dairy processing waste.

The microbial biotransformation using low-cost feedstock to produce biopolymers (degradable), an alternative to petrochemical-based synthesis plastics (non-degradable), can be a beneficial approach towards sustainable development. In this study, the dairy industry processes waste (whey) is used in polyhydroxyalkanoate (PHA) copolymer production. Initial screening suggested that Ralstonia eutropha produced higher PHA as compared to Bacillus megaterium. A central composite rotatable design-based optimization using two process variables (amino acid and tween-80) concentration remarkably influenced PHA co-polymer production under physiological conditions of pH (7), temperature (37 °C), and agitation rate of 150 rpm. High polyhydroxybutyrate (PHB) mass fraction yield of 69.3% was observed as compared to predicted yield of 62.8% from deproteinized whey as feed. The combination of tryptophan (50 mg L-1) and tween-80 (3 mL-1) enhanced R. eutropha mass gain to 6.80 g L-1 with PHB contents of 4.71 g L-1. Further, characterization of PHA and its copolymers was done by ESI-MS, FTIR, and TEM. On upscaling up to 3.0 L, the PHA contents and yields were noted as quite similar by R. eutropha. This study demonstrates that dairy waste processing waste can be potentially utilized as inexpensive feed for producing high content of biopolymers to develop a sustainable system of waste management.

Recent Advances in Monoclonal Antibody-Based Approaches in the Management of Bacterial Sepsis.

Sepsis is a life-threatening condition characterized by an uncontrolled inflammatory response to an infectious agent and its antigens. Immune cell activation against the antigens causes severe distress that mediates a strong inflammatory response in vital organs. Sepsis is responsible for a high rate of morbidity and mortality in immunosuppressed patients. Monoclonal antibody (mAb)-based therapeutic strategies are now being explored as a viable therapy option for severe sepsis and septic shock. Monoclonal antibodies may provide benefits through two major strategies: (a) monoclonal antibodies targeting the pathogen and its components, and (b) mAbs targeting inflammatory signaling may directly suppress the production of inflammatory mediators. The major focus of mAb therapies has been bacterial endotoxin (lipopolysaccharide), although other surface antigens are also being investigated for mAb therapy. Several promising candidates for mAbs are undergoing clinical trials at present. Despite several failures and the investigation of novel targets, mAb therapy provides a glimmer of hope for the treatment of severe bacterial sepsis and septic shock. In this review, mAb candidates, their efficacy against controlling infection, with special emphasis on potential roadblocks, and prospects are discussed.

Therapeutic Approaches in Pancreatic Cancer: Recent Updates.

Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among cancers, pancreatic cancer is also considered a high mortality-causing casualty over other accidental or disease-based mortality, and it is ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic procedures for its early detection, understanding pancreatic cancer-linked mechanisms, and various therapeutic strategies are crucial. This review describes the recent development in pancreatic cancer progression, mechanisms, and therapeutic approaches, including molecular techniques and biomedicines for effectively treating cancer.

Nutritional and Functional New Perspectives and Potential Health Benefits of Quinoa and Chia Seeds.

Quinoa (Chenopodium quinoa Willd) and chia (Salvia hispanica) are essential traditional crops with excellent nutritional properties. Quinoa is known for its high and good quality protein content and nine essential amino acids vital for an individual's development and growth, whereas chia seeds contain high dietary fiber content, calories, lipids, minerals (calcium, magnesium, iron, phosphorus, and zinc), and vitamins (A and B complex). Chia seeds are also known for their presence of a high amount of omega-3 fatty acids. Both quinoa and chia seeds are gluten-free and provide medicinal properties due to bioactive compounds, which help combat various chronic diseases such as diabetes, obesity, cardiovascular diseases, and metabolic diseases such as cancer. Quinoa seeds possess phenolic compounds, particularly kaempferol, which can help prevent cancer. Many food products can be developed by fortifying quinoa and chia seeds in different concentrations to enhance their nutritional profile, such as extruded snacks, meat products, etc. Furthermore, it highlights the value-added products that can be developed by including quinoa and chia seeds, alone and in combination. This review focused on the recent development in quinoa and chia seeds nutritional, bioactive properties, and processing for potential human health and therapeutic applications.

Vinca alkaloids as a potential cancer therapeutics: recent update and future challenges.

Vinca alkaloids including vincristine, vinblastine, vindesine, and vinflunine are chemotherapeutic compounds commonly used to treat various cancers. Vinca alkaloids are one of the first microtubule-targeting agents to be produced and certified for the treatment of hematological and lymphatic neoplasms. Microtubule targeting agents like vincristine and vinblastine work by disrupting microtubule dynamics, causing mitotic arrest and cell death. The key issues facing vinca alkaloids applications include establishing an environment-friendly production technique based on microorganisms, as well as increasing bioavailability without causing harm to patient's health. The low yield of these vinca alkaloids from the plant and the difficulty of meeting their huge colossal demand around the globe prompted researchers to create a variety of approaches. Endophytes could thus be selected to produce beneficial secondary metabolites required for the biosynthesis of vinca alkaloids. This review covers the significant aspects of these vital drugs, from their discovery to the present day, in a concise manner. In addition, we emphasize the major hurdles that must be overcome in the coming years to improve vinca alkaloid's effectiveness.

Role of Matrix Metalloproteinases in Musculoskeletal Diseases.

Musculoskeletal disorders include rheumatoid arthritis, osteoarthritis, sarcopenia, injury, stiffness, and bone loss. The prevalence of these conditions is frequent among elderly populations with significant mobility and mortality rates. This may lead to extreme discomfort and detrimental effect on the patient's health and socioeconomic situation. Muscles, ligaments, tendons, and soft tissue are vital for body function and movement. Matrix metalloproteinases (MMPs) are regulatory proteases involved in synthesizing, degrading, and remodeling extracellular matrix (ECM) components. By modulating ECM reconstruction, cellular migration, and differentiation, MMPs preserve myofiber integrity and homeostasis. In this review, the role of MMPs in skeletal muscle function, muscle injury and repair, skeletal muscle inflammation, and muscular dystrophy and future approaches for MMP-based therapies in musculoskeletal disorders are discussed at the cellular and molecule level.

Recent developments in antimicrobial growth promoters in chicken health: Opportunities and challenges.

With a continuously increasing human population is an increasing global demand for food. People in countries with a higher socioeconomic status tend to switch their preferences from grains to meat and high-value foods. Their preference for chicken as a source of protein has grown by 70% over the last three decades. Many studies have shown the role of feed in regulating the animal gut microbiome and its impact on host health. The microbiome absorbs nutrients, digests foods, induces a mucosal immune response, maintains homeostasis, and regulates bioactive metabolites. These metabolic activities are influenced by the microbiota and diet. An imbalance in microbiota affects host physiology and progressively causes disorders and diseases. With the use of antibiotics, a shift from dysbiosis with a higher density of pathogens to homeostasis can occur. However, the progressive use of higher doses of antibiotics proved harmful and resulted in the emergence of multidrug-resistant microbes. As a result, the use of antibiotics as feed additives has been banned. Researchers, regulatory authorities, and managers in the poultry industry have assessed the challenges associated with these restrictions. Research has sought to identify alternatives to antibiotic growth promoters for poultry that do not have any adverse effects. Modulating the host intestinal microbiome by regulating dietary factors is much easier than manipulating host genetics. Research efforts have led to the identification of feed additives, including bacteriocins, immunostimulants, organic acids, phytogenics, prebiotics, probiotics, phytoncides, and bacteriophages. In contrast to focusing on one or more of these alternative bioadditives, an improved feed conversion ratio with enhanced poultry products is possible by employing a combination of feed additives. This article may be helpful in future research towards developing a sustainable poultry industry through the use of the proposed alternatives.

Polyhydroxyalkanoates: Trends and advances toward biotechnological applications.

Plastics are an integral part of most of the daily requirements. Indiscriminate usage and disposal have led to the accumulation of massive quantities of waste. Their non-biodegradable nature makes it increasingly difficult to manage and dispose them. To counter this impending disaster, biodegradable polymers, especially polyhydroxy-alkanoates (PHAs), have been envisaged as potential alternatives. Owing to their unique physicochemical characteristics, PHAs are gaining importance for versatile applications in the agricultural and medical sectors. Applications in the medical sector are more promising because of their commercial viability and sustainability. Despite such potential, their production and commercialization are significant challenges. The major limitations are their poor mechanical strength, production in small quantities, costly feed, and lack of facilities for industrial production. This article provides an overview of the contemporary progress in the field, to attract researchers and stakeholders to further exploit these renewable resources to produce biodegradable plastics on a commercial scale.

Biomolecules from municipal and food industry wastes: An overview.

Biological wastes generated from food and fruit processing industries, municipal markets, and water treatment facilities are a major cause of concern for Health Departments and Environmentalists around the world. Conventional means of managing these wastes such as transportation, treatment, and disposal, are proving uneconomical. The need is to develop green and sustainable technologies to circumvent this ever-growing and persistent problem. In this article, the potential of diverse microbes to metabolize complex organic rich biowastes into a variety of bioactive compounds with diverse biotechnological applications have been presented. An integrated strategy has been proposed that can be commercially exploited for the recovery of value-adding products ranging from bioactive compounds, chemical building blocks, energy rich chemicals, biopolymers and materials, which results in a self-sustaining circular bioeconomy with nearly zero waste generation and complete degradation.

Inhalable microparticles containing isoniazid and rifabutin target macrophages and 'stimulate the phagocyte' to achieve high efficacy.

Macrophage responses to infection with Mycobacterium tuberculosis (MTB) and treatment with soluble isoniazid (INH) plus rifabutin (RFB) versus microparticles containing equivalent amounts of drugs were compared. It was investigated whether macrophages driven to alternative activation upon infection with MTB could be rescued to display the classical activation phenotype. It was established that microparticles sustain high levels of drugs in cytosol of macrophages for longer period as compared to soluble drugs. Microparticles co-localized with intracellular bacteria, and induced a variety of innate bactericidal responses, including induction of free radicals, alteration of mitochondrial membrane potential and apoptosis. The data strongly suggest that additional benefit may be derived from the nature of the drug delivery system, which fulfils Koch's dictum 'stimulate the phagocyte' for curing tuberculosis.

Hydrogen and polyhydroxybutyrate producing abilities of microbes from diverse habitats by dark fermentative process.

Thirty five bacterial isolates from diverse environmental sources such as contaminated food, nitrogen rich soil, activated sludges from pesticide and oil refineries effluent treatment plants were found to belong to Bacillus, Bordetella, Enterobacter, Proteus, and Pseudomonas sp. on the basis of 16S rRNA gene sequence analysis. Under dark fermentative conditions, maximum hydrogen (H(2)) yields (mol/mol of glucose added) were recorded to be 0.68 with Enterobacter aerogenes EGU16 followed by 0.63 with Bacillus cereus EGU43 and Bacillus thuringiensis EGU45. H(2) constituted 63-69% of the total biogas evolved. Out of these 35 microbes, 18 isolates had the ability to produce polyhydroxybutyrate (PHB), which varied up to 500 mg/l of medium, equivalent to a yield of 66.6%. The highest PHB yield was recorded with B. cereus strain EGU3. Nine strains had high hydrolytic activities (zone of hydrolysis): lipase (34-38 mm) -Bacillus sphaericus strains EGU385, EGU399 and EGU542; protease (56-62 mm) -Bacillus sp. strains EGU444, EGU447 and EGU445; amylase (23 mm) -B. thuringiensis EGU378, marine bacterium strain EGU409 and Pseudomonas sp. strain EGU448. These strains with high hydrolytic activities had relatively low H(2) producing abilities in the range of 0.26-0.42 mol/mol of glucose added and only B. thuringiensis strain EGU378 had the ability to produce PHB. This is the first report among the non-photosynthetic microbes, where the same organism(s) -B. cereus strain EGU43 and B. thuringiensis strain EGU45, have been shown to produce H(2) - 0.63 mol/mol of glucose added and PHB - 420-435 mg/l medium.