Universal slit-lamp mounted indentation gonioscopy tool for angle evaluation: An innovative device.

In the field of ophthalmology, slit-lamp gonioscopy has long been a cornerstone for examining anterior chamber angles and diagnosing conditions such as angle closure, secondary causes of raised intraocular pressure, neovascularization of angle, angle recession, angle tumors, and foreign bodies. However, the conventional approach for goniophotography is a demanding procedure requiring juggling a gonioscopy lens in one hand and a smartphone in the other. Balancing a gonioscopy lens with one hand makes it difficult to adjust and focus the image in busy clinical settings. This article introduces a groundbreaking solution to this problem - a universal slit-lamp-mounted gonioscope ingeniously repurposed from discarded materials, that is, indirect goniophotography (IndiGo). This novel system simplifies the process of both gonioscopy and goniophotography, allowing ophthalmologists to easily assess anterior chamber angles and capture high-quality images. These images can be swiftly shared with glaucoma specialists worldwide for digital analysis. Not only does this approach enhance examination efficiency, but also it fosters sustainability in ophthalmic diagnostics.

Ophthalmic manifestations as the first presenting feature in dengue fever: a 10-year study.

Purpose: To report patients who first presented with various ocular manifestations and eventually ascertained to have underlying dengue. Methods: A prospective study was conducted at multiple tertiary eye-care centers in India from 2012 to 2022. Cases reporting initially with ocular features along with fever/past history of fever over the last two weeks or with clinical features of dengue were selected. After an ophthalmological examination, patients underwent complete serological and biochemical analysis and those with reduced platelet counts were evaluated for dengue. Results: Out of 564 cases, 15 patients were verified to be afflicted with dengue eventually. A rising trend of cases was seen every year and out of 15 cases, eight cases were reported during the Covid-19 pandemic (from 2020 to 2022), but were COVID-negative. 9 cases presented with acute redness followed by diminished vision. Seven cases presented a history of fever over the last few days and one had traveled from dengue endemic area. The various ocular presentations included subconjunctival hemorrhage, viral keratitis, anterior uveitis, sixth-nerve palsy, and vitreous hemorrhage. On serological examination, all 15 patients were detected to have low platelets. All cases responded well with supportive treatment and the ocular features subsided in all within a couple of weeks with good visual recovery. Conclusion: In a tropical nation, such as India, with endemic dengue zones and increasing figures of dengue lately, ophthalmologists must include dengue fever among the differential diagnoses in various ocular presentations like subconjunctival hemorrhage, viral keratitis, anterior uveitis, sixth nerve palsy, and vitreous hemorrhage. Abbreviations: DHF = dengue hemorrhagic fever, PCR = polymerase chain reaction, RT-PCR = real-time automated reverse transcriptase (RT-PCR), SD = standard deviation, MAC-ELIS = IgM antibodies capture enzyme-linked immunosorbent assay, RE = right eye, LE = left eye, CECT = Contrast-enhanced computed tomography.

Metabolite Profiling, Biological and Molecular Analyses Validate the Nutraceutical Potential of Green Seaweed Acrosiphoniaorientalis for Human Health.

Seaweeds have proven to be nutrient-dense and are rich in antioxidants, like phenolics, flavonoids, and other essential metabolites that help to provide their medicinal benefits. Non-targeted metabolite profiling of the tropical green seaweed Acrosiphonia orientalis showed the presence of numerous groups of contents, including sugars, essential amino acids, and fatty acids. Targeted metabolite profiling using HPLC identified 17 amino acids. The extract exhibited a very low half-maximal effective concentration (EC50) dosage for HeLa and Huh-7 cell lines, indicating a high likelihood of anticancer properties. A significant positive correlation was found between biological activities, such as antioxidation, scavenging, and reducing power with the phenolic and flavonoid contents. The extract revealed augmentation of proliferation in selected cervical cells, as it upregulated p53 1.3-fold, and downregulated important cancerous genes such as Cas-3 and DNMT 12- and 8-fold, respectively. An approximate 55-fold downregulation was observed in selected hepatic cell lines. Microarray analysis of hepatic cells indicated 0.27% and 0.07% upregulation of coding and non-coding genes, respectively, and 0.41% and 0.13% downregulation of coding and non-coding genes, respectively. As a consequence, it can be said that A. orientalis has possible medicinal use, such as anticancer activity, and therefore may be an intriguing food component that has potential as a regular dietary supplement.

Differentiating stable and unstable protein using convolution neural network and molecular dynamics simulations.

Protein stability is a critical aspect of molecular biology and biochemistry, hinges on an intricate balance of thermodynamic and structural factors. Determining protein stability is crucial for understanding and manipulating biological machineries, as it directly correlated with the protein function. Thus, this study delves into the intricacies of protein stability, highlighting its dependence on various factors, including thermodynamics, thermal conditions, and structural properties. Moreover, a notable focus is placed on the free energy change of unfolding (ΔGunfolding), change in heat capacity (ΔCp) with protein structural transition, melting temperature (Tm) and number of disulfide bonds, which are critical parameters in understanding protein stability. In this study, a machine learning (ML) predictive model was developed to estimate these four parameters using the primary sequence of the protein. The shortfall of available tools for protein stability prediction based on multiple parameters propelled the completion of this study. Convolutional Neural Network (CNN) with multiple layers was adopted to develop a more reliable ML model. Individual predictive models were prepared for each property, and all the prepared models showed results with high accuracy. The R2 (coefficient of determination) of these models were 0.79, 0.78, 0.92 and 0.92, respectively, for ΔG, ΔCp, Tm and disulfide bonds. A case study on stability analysis of two homologous proteins was presented to validate the results predicted through the developed model. The case study included in silico analysis of protein stability using molecular docking and molecular dynamic simulations. This validation study assured the accuracy of each model in predicting the stability associated properties. The alignment of physics-based principles with ML models has provided an opportunity to develop a fast machine learning solution to replace the computationally demanding physics-based calculations used to determine protein stability. Furthermore, this work provided valuable insights into the impact of mutation on protein stability, which has implications for the field of protein engineering. The source codes are available at https://github.com/Growdeatechnology.

A Comparative Study on Efficacy of Intraocular Pressure Lowering of Two Fixed-Dose Antiglaucoma Drug Combination Brinzolamide-Brimonidine Versus Latanoprost-Timolol in Primary Open-Angle Glaucoma and Ocular Hypertension.

Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.

A Randomized Controlled Trial Comparing Face-to-Face Versus Remote Delivery of Low-Tech Augmentative and Alternative Communication in Nonspeaking Children With Autism Spectrum Disorder.

PURPOSE: Thirty percent of children diagnosed with autism spectrum disorder (ASD) do not develop spoken language. To provide a means of communication for this subset of the population, augmentative and alternative communication (AAC) systems are often utilized. Low-tech options have traditionally been delivered through the in-person modality. However, due to the COVID-19 pandemic, changes to service delivery models have been required. This randomized controlled trial was conducted in order to assess the efficacy of low-tech AAC delivered face-to-face versus remotely on communication outcomes in nonspeaking children with ASD. CONCLUSIONS: Both participant groups demonstrated similar gains in AAC proficiency, number and type of nonspeaking acts, and number of spoken communication acts. Remote delivery of low-tech AAC treatment is a viable alternative to face-to-face instruction.

Cholesterol Absorption Inhibition by Some Nutraceuticals.

Hyperlipidemia, characterized by elevated levels of lipids in the blood, represents a major risk factor for cardiovascular diseases, a leading cause of morbidity and mortality worldwide. Conventional pharmacological interventions have been effective in managing hyperlipidemia, but concerns about side effects and long-term use have prompted interest in alternative approaches, particularly the use of nutraceuticals. This comprehensive review aims to summarize and critically evaluate the current body of knowledge surrounding the role of nutraceuticals in the management of hyperlipidemia. We provide an overview of the different classes of nutraceuticals, including plant sterols, omega-3 fatty acids, soluble fiber, antioxidants, and various herbal extracts, which have been investigated for their lipid-lowering properties. The mechanisms of action of these nutraceuticals are discussed, highlighting their ability to modulate lipid metabolism, reduce oxidative stress, and promote cardiovascular health. Furthermore, we review the results of clinical trials and epidemiological studies that have assessed the efficacy of nutraceutical interventions in lowering cholesterol levels, improving lipid profiles, and reducing the risk of cardiovascular events. In addition to their lipid-lowering effects, we examine the safety profile, dosage recommendations, and potential interactions of nutraceuticals with conventional lipid-lowering medications. We also address the importance of patient adherence to dietary and lifestyle modifications in conjunction with nutraceutical supplementation. While nutraceuticals offer a promising avenue for managing hyperlipidemia, we emphasize the need for further research to establish evidence-based guidelines for their use in clinical practice. Challenges related to standardization, quality control, and regulatory considerations are also discussed. In conclusion, this comprehensive review provides valuable insights into the potential of nutraceuticals as adjunctive or alternative therapies for managing hyperlipidemia. While further research is needed, the accumulating evidence suggests that nutraceuticals can play a valuable role in promoting cardiovascular health and reducing the burden of hyperlipidemia- related diseases.

Rehashing Our Insight of Seaweeds as a Potential Source of Foods, Nutraceuticals, and Pharmaceuticals.

In a few Southeast Asian nations, seaweeds have been a staple of the cuisine since prehistoric times. Seaweeds are currently becoming more and more popular around the world due to their superior nutritional value and medicinal properties. This is because of rising seaweed production on a global scale and substantial research on their composition and bioactivities over the past 20 years. By reviewing several articles in the literature, this review aimed to provide comprehensive information about the primary and secondary metabolites and various classes of bioactive compounds, such as polysaccharides, polyphenols, proteins, and essential fatty acids, along with their bioactivities, in a single article. This review also highlights the potential of seaweeds in the development of nutraceuticals, with a particular focus on their ability to enhance human health and overall well-being. In addition, we discuss the challenges and potential opportunities associated with the advancement of pharmaceuticals and nutraceuticals derived from seaweeds, as well as their incorporation into different industrial sectors. Furthermore, we find that many bioactive constituents found in seaweeds have demonstrated potential in terms of different therapeutic attributes, including antioxidative, anti-inflammatory, anticancer, and other properties. In conclusion, seaweed-based bioactive compounds have a huge potential to play an important role in the food, nutraceutical, and pharmaceutical sectors. However, future research should pay more attention to developing efficient techniques for the extraction and purification of compounds as well as their toxicity analysis, clinical efficacy, mode of action, and interactions with regular diets.

Prevent, curtail and mitigate ocular injuries: Proposal for designing an eye injury registry model for the Indian Armed Forces.

This article aims to propose a design for Eye Injury Registry (EIR) model for Indian Armed Forces, to make ophthalmologists and non-ophthalmologists aware about the existence as well as the usefulness of such a registry. This is a perspective study. The EIR model for Armed Forces was designed based on the relevant sources in PubMed, Scopus and Embase including registries of pioneering countries like United States and Canada. A questionnaire based on the model dimensions was developed (Cronbach's alpha>0.7) and filled by 04 senior ophthalmologists in Armed Forces, all of who had a significant experience in dealing with various types of ocular trauma, to give expert opinions, which were then applied to the proposed model to finalize it. In Armed Forces, a registry and reporting on eye injury along with a systematic collection of standard data on eye injuries will help ophthalmologists in the successful prevention. Such a registry and its large database once formed will permit elaborate epidemiologic investigations, highlighting preventable sources of injury, emerging patterns of trauma in our services, and the best possible treatment protocols to be adopted, for successful outcomes. EIR in Armed Forces can help in the collection of eye injury data, thereby improving the quality-of-care and expansion of prevention strategies for ocular injuries. It is a step to make a truly effective data bank, which will be instrumental in combating such preventable ocular injuries and in turn go a very long way in achieving the final goal of preventing up to 90% of such injuries.

Nutrient Composition, Physicobiochemical Analyses, Oxidative Stability and Antinutritional Assessment of Abundant Tropical Seaweeds from the Arabian Sea.

Foods enriched with nutritional compounds and biological activities, especially antioxidants, are considered healthier for human and/or animal consumption. Seaweeds are rich sources of biologically active metabolites and are used as functional foods. In this study, proximate compositions, physicobiochemical characteristics and oil oxidative stability were analyzed for 15 abundant tropical seaweeds (four green-Acrosiphonia orientalis, Caulerpa scalpelliformis, Ulva fasciata, Ulva lactuca; six brown-Iyengaria stellata, Lobophora variegate, Padina boergesenii, Sargassum linearifolium, Spatoglossum asperum, Stoechospermum marginatum; and five red-Amphiroa anceps, Grateloupia indica, Halymenia porphyriformis, Scinaia carnosa, Solieria chordalis). All seaweeds were analyzed for the proximate composition, including moisture content, ash content, total sugar content, total proteins, total lipids, crude fiber, carotenoid content, total chlorophyll content, proline, iodine content, nitrogen-free extract, total phenolic content and total flavonoid content. Green seaweeds showed higher nutritional proximate composition, followed by brown and red seaweeds. Among the different seaweeds, Ulva, Caulerpa, Sargassum, Spatoglossum and Amphiroa showed high nutritional proximate composition compared to other seaweeds. High cation scavenging, free radical scavenging and total reducing activities were observed for Acrosiphonia, Caulerpa, Ulva, Sargassum, Spatoglossum and Iyengaria. It was also observed that 15 tropical seaweeds contained negligible amounts of antinutritional compounds, including tannic acid, phytic acid, saponins, alkaloids and terpenoids. Nutritionally, green and brown seaweeds provided higher sources of energy (150-300 calories per 100 g) compared to red seaweeds (80-165 calories per 100 g). Additionally, this study also confirmed that tropical seaweeds improved the oxidative stability of food oils and, therefore, might be recommended as natural antioxidant additives. The overall results confirm that tropical seaweeds are potential sources of nutrition and antioxidants and may be explored as functional food, dietary supplementation or animal feed. Additionally, they may also be explored as food supplements for fortifying food products, as food toppings or for garnishing and seasoning foods. However, a human or animal toxicity analysis is required before any conclusive recommendation for daily food or feed intake can be made.

Universal slit-lamp-mounted mobile adapter with 20 D lens for fundus photography: "Litter to glitter".

Fundus photography is an arduous task as it involves using 90 D in one hand and a smartphone attached on an eyepiece of a slit-lamp biomicroscope in the other hand. Similarly, with a 20 D lens, the filming distance is adjusted by moving the lens or mobile forward or backward, which makes it difficult to adjust and focus the image in busy ophthalmology outpatient departments (OPDs). Moreover, fundus camera costs thousands of dollars. Authors describe a novel technique of performing fundus photography with a 20 D lens and a universal slit-lamp-mounted mobile adapter made from trash. By the use of this simple, yet frugal innovation, primary care physicians or ophthalmologists without a fundus camera can easily snap a fundus photo and subject it to digital analysis by retina specialists across the world. This will help in simultaneous ocular examination and fundus photos taken via mounted 20 D on a slit lamp itself and also reduce the need for unnecessary retina referrals to tertiary eye care centers.

Intrastromal voriconazole as successful adjunctive approach for recalcitrant deep fungal keratitis.

Aim: To assess efficacy of intrastromal voriconazole (ISV) in the treatment of fungal keratitis non-responding to conventional antifungals. Methods: Eighteen patients with smear positive fungal keratitis, not responding to conventional topical/ systemic antifungal therapy up to 2 weeks, were included in the study. Afterwards, they were given ISV (50 µg in 0.1 ml) around the ulcer and continued to receive conventional antifungal therapy. Responses to treatment (decrease in size of the ulcer and infiltrates) were recorded daily for 3-days, at 1-week and every 2 weeks for 3-months, or until the ulcer had healed completely. Results: The mean age at presentation was 51 ± 17.83 years. The most common organism isolated was Fusarium (17/ 18), followed by Aspergillus (1/ 18). All the patients were successfully treated in terms of corneal healing, but one case did not improve in vision due to the existence of diabetic macular oedema. 6 patients improved after a single injection, 7 had to receive 2 and 5 improved after 3 injections. The mean number of injections in 17 treated patients was 1.94 ± 0.78. Moreover, the mean resolution time was 18.50 ± 6.25 days. The size of ulcer and height of hypopyon at presentation were noteworthy risk-factors linked to management outcomes. Deeper ulcers required a greater number of injections when compared to superficial ulcers. The mean best-corrected visual acuity improved from 0.94 to 0.25 at 3 months follow-up in all the patients. Conclusion: Intrastromal Voriconazole (50 µg/ 0.1 mL) appears to be an effective adjunct therapy in cases of recalcitrant deep fungal keratitis non-responding to conventional antifungals. Though, some may require repeated injections, timely ISV administration certainly reducing the need for tectonic/ therapeutic keratoplasty. Abbreviations: ISV = Intrastromal Voriconazole, AS-OCT = anterior-segment optical coherence topography, KOH = potassium hydroxide, BCVA = best-corrected visual acuity.

Dry eye disease survey among schoolteachers and children using visual display terminals during COVID-19 lockdown-CODE study ( Co vid and d ry e ye study).

Background: Lockdown during COVID-19 led to teachers and children shifting to online classes, using visual display terminals (VDTs) for education, resulting in increased screen time. The present study was done to assess and understand the nature and magnitude of the problem and to suggest preventive or remedial measures. Methods: A questionnaire-based cross-sectional study was conducted. The questionnaire was prepared for an online survey (using Google Forms) and circulated among school children belonging to different schools across India using multiple groups on social media. Results: A total of 3327 participants from 46 schools across India participated in the survey. We found a marked rise in cumulative screen time for both teachers and students before and during the lockdown. There was a threefold increase in the number of participants with a cumulative screen time 6 h or more compared to the pre-COVID era. Teachers (older participants) had worse symptom scores than students. Larger screens, like televisions, were better VDTs compared to smartphones, tablets, or laptops. Conclusions: School administrators and policymakers should pay due attention to institutionalizing the guidelines about class duration, appropriate screens, and stipulating break duration during online classes, which will continue to remain the predominant mode of education for teachers and students alike, at least in the near future.

Bio-Stimulating Effect of Natural Polysaccharides from Lobularia maritima on Durum Wheat Seedlings: Improved Plant Growth, Salt Stress Tolerance by Modulating Biochemical Responses and Ion Homeostasis.

Bioactivities of polysaccharides derived from halophyte plants have gained attention in recent years. The use of biostimulants in agriculture is an innovative method of dealing with environmental stressors affecting plant growth and development. Here, we investigated the use of natural polysaccharides derived from the halophyte plant Lobularia maritima (PSLm) as a biostimulant in durum wheat seedlings under salt stress. Treatment with polysaccharide extract (0.5, 1, and 2 mg/mL PSLm) stimulated in vitro wheat growth, including germination, shoot length, root length, and fresh weight. PSLm at 2 mg/mL provided tolerance to plants against NaCl stress with improved membrane stability and low electrolyte leakage, increased antioxidant activities (catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD)), enhanced leaf chlorophyll fluorescence, proline, and total sugar contents, decreased lipid peroxidation (MDA), and reactive oxygen species (H2O2) levels, and coordinated the efflux and compartmentation of intracellular ions. The expression profile analyses of ten stress-related genes (NHX1, HKT1.4, SOS1, SOD, CAT, GA20-ox1, GA3-ox1, NRT1.1, NRT2.1, and GS) using RT-qPCR revealed the induction of several key genes in durum wheat growing in media supplemented with PSLm extract, even in unstressed conditions that could be related to the observed tolerance. This study revealed that PSLm extract contributes to salt tolerance in durum wheat seedlings, thereby enhancing their reactive oxygen species scavenging ability, and provided evidence for exploring PSLm as a plant biostimulant for sustainable and organic agriculture.

Introgression of a novel gene AhBINR differentially expressed during PGPR Brachybacterium saurashtrense-Arachis hypogaea interaction enhances plant performance under nitrogen starvation and salt stress in tobacco.

Plant growth-promoting rhizobacteria provide endurance during environmental stress conditions. Previously, we have shown that the interaction of the halotolerant diazotrophic bacteria Brachybacterium saurashtrense JG06 induces physio-biochemical and molecular changes in Arachis hypogaea under nitrogen starvation conditions. Here we deciphered the role of a novel gene AhBINR that was differentially overexpressed in A. hypogaea after interaction with B. saurashtrense JG06 under nitrogen deficit conditions. Overexpression of the AhBINR gene in the model plant (tobacco) showed higher growth parameters (root length, shoot length, fresh weight, and dry weight) under nitrogen starvation and salt stress in comparison to the wild type and vector control. Transgenic plants were enabled with a higher photosynthesis rate, which provides the support for better performance under N2 starvation and salt stress. Results showed that the transgenic plants overexpressing the AhBINR gene had better physiological status and lower ROS accumulation under adverse conditions. Microarray transcriptome analysis showed that the transcription factors, biotic and abiotic stress, photosynthesis, and metabolism-related genes were differentially expressed (total 736 and 6530 genes were expressed under nitrogen deficit and salt stress conditions, respectively at a 5-fold change level) in comparison to wild type plants. Overall results showed the involvement of the AhBINR gene in the activation of the abiotic stress (nitrogen starvation and salt stress) related pathways, which can be overexpressed after legume-rhizobacterial interaction.

Development of instant paneer type product from groundnut using microwave dehydration.

The present study aimed at the development of a groundnut-based dehydrated paneer type product which could serve as an instant vegan protein source. In the process of preparing groundnut paneer, a ratio of 1:5 of groundnut to water and 2.0% calcium chloride (CaCl2) solution was used for the preparation of groundnut paneer and the product was evaluated for physicochemical, instrumental color, instrumental textural, and sensory characteristics. The developed paneer cubes (1.5 × 1.5 × 1 cm) were dehydrated using a vacuum-assisted microwave dryer at different microwave powers (200-600 W, 250 mbar vacuum). The minimum bulk density (0.55 g/cc) and maximum rehydration ratio (2.9) were recorded in the sample dehydrated at 600 W. The samples dried at 600 W also showed significantly (p < .05) higher L* values, softer texture and high sensory scores for color, aroma, taste, texture, and overall acceptability after rehydration.

Green-synthesized, pH-stable and biocompatible carbon nanosensor for Fe3+: An experimental and computational study.

Brightly fluorescent Carbon Dots (CDs) were synthesized by green hydrothermal method using commonly available biomass (Aloe vera) as carbon precursor. Their physiochemical and optical characterization was done by standard microscopic and spectroscopic techniques. Photophysical features of their aqueous dispersion were investigated in detail. The influence of wide pH range (2-12), high ionic load (2M) and temperature on their photoluminescence behavior was investigated. Their in-vitro cytotoxicity examination was conducted on Human Cervical Cancer Cells (HeLa) using MTT assay. Testing of their ion-recognition property for common metal ions was done in aqueous medium. These CDs exhibited preferential interaction with Fe3+ over other tested metal ions, without any functionalization. Interaction between CDs and Fe3+ was analyzed in the light of Density Functional Theory (DFT). The work demonstrates that these CDs are acting as nanoprobe for Fe3+ and sensing it at ultra-trace level (5 nM).

Dimerization of SARS-CoV-2 nucleocapsid protein affects sensitivity of ELISA based diagnostics of COVID-19.

Nucleocapsid protein (N protein) is the primary antigen of the virus for development of sensitive diagnostic assays of COVID-19. In this paper, we demonstrate the significant impact of dimerization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N-protein on sensitivity of enzyme-linked immunosorbent assay (ELISA) based diagnostics. The expressed purified protein from E. coli is composed of dimeric and monomeric forms, which have been further characterized using biophysical and immunological techniques. Indirect ELISA indicated elevated susceptibility of the dimeric form of the nucleocapsid protein for identification of protein-specific monoclonal antibody as compared to the monomeric form. This finding also confirmed with the modelled structure of monomeric and dimeric nucleocapsid protein via HHPred software and its solvent accessible surface area, which indicates higher stability and antigenicity of the dimeric type as compared to the monomeric form. The sensitivity and specificity of the ELISA at 95% CI are 99.0% (94.5-99.9) and 95.0% (83.0-99.4), respectively, for the highest purified dimeric form of the N protein. As a result, using the highest purified dimeric form will improve the sensitivity of the current nucleocapsid-dependent ELISA for COVID-19 diagnosis, and manufacturers should monitor and maintain the monomer-dimer composition for accurate and robust diagnostics.

Differential Physio-Biochemical and Metabolic Responses of Peanut (Arachis hypogaea L.) under Multiple Abiotic Stress Conditions.

The frequency and severity of extreme climatic conditions such as drought, salinity, cold, and heat are increasing due to climate change. Moreover, in the field, plants are affected by multiple abiotic stresses simultaneously or sequentially. Thus, it is imperative to compare the effects of stress combinations on crop plants relative to individual stresses. This study investigated the differential regulation of physio-biochemical and metabolomics parameters in peanut (Arachis hypogaea L.) under individual (salt, drought, cold, and heat) and combined stress treatments using multivariate correlation analysis. The results showed that combined heat, salt, and drought stress compounds the stress effect of individual stresses. Combined stresses that included heat had the highest electrolyte leakage and lowest relative water content. Lipid peroxidation and chlorophyll contents did not significantly change under combined stresses. Biochemical parameters, such as free amino acids, polyphenol, starch, and sugars, significantly changed under combined stresses compared to individual stresses. Free amino acids increased under combined stresses that included heat; starch, sugars, and polyphenols increased under combined stresses that included drought; proline concentration increased under combined stresses that included salt. Metabolomics data that were obtained under different individual and combined stresses can be used to identify molecular phenotypes that are involved in the acclimation response of plants under changing abiotic stress conditions. Peanut metabolomics identified 160 metabolites, including amino acids, sugars, sugar alcohols, organic acids, fatty acids, sugar acids, and other organic compounds. Pathway enrichment analysis revealed that abiotic stresses significantly affected amino acid, amino sugar, and sugar metabolism. The stress treatments affected the metabolites that were associated with the tricarboxylic acid (TCA) and urea cycles and associated amino acid biosynthesis pathway intermediates. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and heatmap analysis identified potential marker metabolites (pinitol, malic acid, and xylopyranose) that were associated with abiotic stress combinations, which could be used in breeding efforts to develop peanut cultivars that are resilient to climate change. The study will also facilitate researchers to explore different stress indicators to identify resistant cultivars for future crop improvement programs.

Pharmacophore screening to identify natural origin compounds to target RNA-dependent RNA polymerase (RdRp) of SARS-CoV2.

Several existing drugs have gained initial consideration due to their therapeutic characteristics against COVID-19 (Corona Virus Disease 2019). Hydroxychloroquine (HCQ) was proposed as possible therapy for shortening the duration of COVID-19, but soon after this, it was discarded. Similarly, known antiviral compounds were also proposed and investigated to treat COVID-19. We report a pharmacophore screening using essential chemical groups derived from HCQ and known antivirals to search a natural compound chemical space. Molecular docking of HCQ under physiological condition with spike protein, 3C-like protease (3CLpro), and RNA-dependent RNA polymerase (RdRp) of SARS-CoV2 showed - 8.52 kcal/mole binding score with RdRp, while the other two proteins showed relatively weaker binding affinity. Docked complex of RdRp-HCQ is further examined using 100 ns molecular dynamic simulation. Docking and simulation study confirmed active chemical moieties of HCQ, treated as 6-point pharmacophore to screen ZINC natural compound database. Pharmacophore screening resulted in the identification of potent hit molecule [(3S,3aR,6R,6aS)-3-(5-phenylsulfanyltetrazol-1-yl)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]N-naphthalen-ylcarbamate from natural compound library. Additionally, a set of antiviral compounds with similar chemical scaffolds are also used to design a separate ligand-based pharmacophore screening. Antiviral pharmacophore screening produced a potent hit 4-[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-(2-hydroxyphenyl)methyl]-1,5-dimethyl-2-phenylpyrazol-3-one containing essential moieties that showed affinity towards RdRp. Further, both these screened compounds are docked (- 8.69 and - 8.86 kcal/mol) and simulated with RdRp protein for 100 ns in explicit solvent medium. They bind at the active site of RdRp and form direct/indirect interaction with ASP618, ASP760, and ASP761 catalytic residues of the protein. Successively, their molecular mechanics Poisson Boltzmann surface area (MMPBSA) binding energies are calculated over the simulation trajectory to determine the dynamic atomistic interaction details. Overall, this study proposes two key natural chemical moieties: (a) tetrazol and (b) phenylpyrazol that can be investigated as a potential chemical group to design inhibitors against SARS-CoV2 RdRp.