Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol.

In the current work, we analyzed the origin of difference in stabilities among the germacrene A and hedycaryol-derived carbocations. This study focused on twelve hydrocarbons derived from germacrene A and twelve from hedycaryol, which can be divided into three groups: four molecules containing 6-6 bicyclic rings, four 5-7 bicyclic compounds with the carbocation being on the seven-membered ring and the remaining four 5-7 bicyclic compounds with the carbocation on the five-membered ring. The variations in energy within the groups of carbocations (i.e., 6-6 and two kinds of 5-7 bicyclic carbocations) can be ascribed to intramolecular repulsion interactions, as seen from non-covalent interactions plots. Despite the structural similarities between germacrene A and hedycaryol cations, they possess a somewhat different stability trend. These differences are attributed to C+···OH intramolecular interactions present in some hedycaryol cations, which are absent in the carbocations derived from germecrene A.

Antimicrobial therapeutic protein extraction from fruit waste and recent trends in their utilization against infections.

Fruits are a very good source of various nutrients that can boost overall human health. In these days, the recovery of therapeutic compounds from different fruit wastes is trending in research, which might not only minimize the waste problem but also encounter a higher demand for various enzymes that could have antimicrobial properties against infectious diseases. The goal of this review is to focus on the recovery of therapeutic enzymes from fruit wastes and its present-day tendency for utilization. Here we discussed different parts of fruit waste, such as pulp, pomace, seed, kernel, peel, etc., that produce therapeutic enzymes like amylase, cellulose, lipase, laccase, pectinase, etc. These bioactive enzymes are present in different parts of fruit and could be used as therapeutics against various infectious diseases. This article provides a thorough knowledge compilation of therapeutic enzyme isolation from fruit waste on a single platform, distinctly informative, and significant review work on the topic that is envisioned to encourage further research ideas in these areas that are still under-explored. This paper explains the various aspects of enzyme isolation from fruit and vegetable waste and their biotherapeutic potential that could provide new insights into the development of biotherapeutics and attract the attention of researchers to enhance translational research magnitude further.

Development of Simultaneous HPTLC Method and Validation for the Quality Assessment of Ayurvedic Formulation-Ayush Kvatha Churna by Using Marker Compound Rosmarinic Acid, Trans-Cinnamaldehyde and Piperine.

Ayurveda emphasizes the propagation of nature in maintaining health. In the present scenario, we have seen the faith of people in herbal drugs during the Covid 19 outbreak. The raises in the number of peoples have been using herbal drugs to boost immunity against infectious diseases shows the popularity of this ancient system of medicine. The standardization of Ayush Kvatha Churna (AKC), work set out to establish a straightforward, accurate and sensitive HPTLC method for the identification and quantification of marker compounds. The Rosmarinic acid, trans-Cinnamaldehyde and Piperine were used for the estimation of markers in Ayush Kvatha Churna by using HPTLC with a solvent system, consisting of Toluene: Ethyl acetate: Ethyl alcohol: Formic acid (5.6:2.4:2: 0.3 v/v/v/v). The Rf value 0.33 for Rosmarinic Acid, 0.69 for Piperine and 0.77 for trans-Cinnamaldehyde was observed and it is exactly complying with the corresponding bands in Ayush Kvatha Churna. The technique has been effectively verified and validated, enabling it to be used for the standardization or quantitative analysis of Rosmarinic acid, trans-Cinnamaldehyde and piperine in Ayush Kvatha Churna.

Electronic Tongue Based on ZnO/ITO@glass for Electrochemical Monitoring of Spiciness Levels.

Capsaicin, a chemical compound present in chili peppers, is widely acknowledged as the main contributor to the spicy and hot sensations encountered during consumption. Elevated levels of capsaicin can result in meals being excessively spicy, potentially leading to health issues, such as skin burning, irritation, increased heart rate and circulation, and discomfort in the gastrointestinal system and even inducing nausea or diarrhea. The level of spiciness that individuals can tolerate may vary, so what may be considered incredibly hot for one person could be mild for another. To ensure food safety, human healthcare, regulatory compliance, and quality control in spicy food products, capsaicin levels must be measured. For these purposes, a reliable and stable sensor is required to quantify the capsaicin level. To leverage the effect of zinc oxide (ZnO), herein, we demonstrated the one-step fabrication process of an electronic tongue (E-Tongue) based on an electrochemical biosensor for the determination of capsaicin. ZnO was electrodeposited on the indium tin oxide (ITO) surface. The biosensor demonstrated the two notable linear ranges from 0.01 to 50 µM and from 50 to 500 µM with a limit of detection (LOD) of 2.1 nM. The present study also included the analysis of real samples, such as green chilis, red chili powder, and dried red chilis, to evaluate their spiciness levels. Furthermore, the E-Tongue exhibited notable degrees of sensitivity, selectivity, and long-term stability for a duration of more than a month. The development of an E-Tongue for capsaicin real-time monitoring as a point-of-care (POC) device has the potential to impact various industries and improve safety, product quality, and healthcare outcomes.

VWD domain stabilization by autocatalytic Asp-Pro cleavage.

Domains known as von Willebrand factor type D (VWD) are found in extracellular and cell-surface proteins including von Willebrand factor, mucins, and various signaling molecules and receptors. Many VWD domains have a glycine-aspartate-proline-histidine (GDPH) amino-acid sequence motif, which is hydrolytically cleaved post-translationally between the aspartate (Asp) and proline (Pro). The Fc IgG binding protein (FCGBP), found in intestinal mucus secretions and other extracellular environments, contains 13 VWD domains, 11 of which have a GDPH cleavage site. In this study, we investigated the structural and biophysical consequences of Asp-Pro peptide cleavage in a representative FCGBP VWD domain. We found that endogenous Asp-Pro cleavage increases the resistance of the domain to exogenous proteolytic degradation. Tertiary structural interactions made by the newly generated chain termini, as revealed by a crystal structure of an FCGBP segment containing the VWD domain, may explain this observation. Notably, the Gly-Asp peptide bond, upstream of the cleavage site, assumed the cis configuration in the structure. In addition to these local features of the cleavage site, a global organizational difference was seen when comparing the FCGBP segment structure with the numerous other structures containing the same set of domains. Together, these data illuminate the outcome of GDPH cleavage and demonstrate the plasticity of proteins with VWD domains, which may contribute to their evolution for function in a dynamic extracellular environment.

Molecular simulations of understanding the Na+ ion structure, dynamic and thermodynamic behavior in ionic liquids: Butyl ammonium hydrogen bisulfate and tri-butyl ammonium hydrogen bisulfate.

This manuscript presents the all-atom molecular dynamics simulations to investigate intermolecular structure and solvation thermodynamics of Na+ ion in two different ammonium-based protic ionic liquids (1) Butyl Ammonium hydrogen bisulfate [BA+][HSO4-], (2) Tri-butyl ammonium hydrogen bisulfate [TBA+][HSO4-]. The ionic liquid [BA+][HSO4-] show a more coordinated behavior when compared to [TBA+][HSO4-], which is observed over the temperature range from 278 K to 348 K. Hydrogens of the cations show a hydrogen bonding interaction with oxygens of anions. The cationic [TBA+] molecules show more solvation behavior with anions when compared to the [BA+]. The Na+ ion show a strong coordination structure with [HSO4-] in [TBA+][HSO4-] when compared to the [BA+][HSO4-]. We further calculate the detailed solvation free energy (ΔG) calculations using thermodynamic integration. We found that the ΔG of Na+ is more favorable in [TBA+][HSO4-] when compared to [BA+][HSO4-] in the temperature range varying from 278 K to 348 K. With the temperature rise, we observe the more favorable solvation of Na+ in both ionic liquids. On the other hand, the solvation of Cl- becomes less favorable. Overall, this manuscript provides detailed molecular level structural and thermodynamic origins of Na+ in protic ionic liquids useful for designing and developing sustainable electrolytes for Na+ battery applications.

Origin of Catalysis by Nitroalkane Oxidase.

The rate of proton abstraction of the carbon acid nitroethane by Asp402 is accelerated by a factor of 108 in the enzyme nitroalkane oxidase (NAO) relative to that by the organic base acetate ion in water. The Cα proton of nitroalkanes is known to exhibit an abnormal correlation between its acidity strength and the rate of deprotonation, with an unusually slow rate of deprotonation in water. This work examines the origin of NAO catalysis, revealing that the rate enhancement by the enzyme is due to transition-state stabilization, restoring the normal behavior of the linear free energy relationship of Bronsted acids. Interestingly, NAO employs the ubiquitous cofactor flavin adenosine diphosphate (FAD) to perform the subsequent oxidation. Does the FAD cofactor also affect the catalytic rate of the initial proton transfer process of the overall nitroalkane oxidation? Classical molecular dynamics and path-integral simulations using a reaction-specific combined quantum mechanics/molecular mechanics (QM/MM) approach were carried out to obtain the free energy reaction profiles, or the potentials of mean force, for the enzymatic reaction and for a model reaction in aqueous solution, as well as for the 2'-deoxy-FAD co-factor-modified NAO. Free energy perturbation calculations suggest that transition-state stabilization of the reactive fragment is the primary cause of the catalytic effect. It is found that the FAD cofactor plays a crucial role in increasing the Cα proton acidity, via specific hydrogen bonding and π-stacking interactions, although these factors have a smaller effect on the enhancement of the rate of deprotonation. Model QM calculations of the π-stacking complexes between the FAD isoalloxazine ring and the neutral and anionic nitroethane, respectively, reveal that the anionic π-stacking complex is more stable than the neutral one by 15.7 kcal/mol, and a net π-stacking energy of 17.3 kcal/mol is obtained. Hence, the isoalloxazine ring, in addition to serving as a very potent oxidizing agent via the formation of covalent intermediate structures, is able to exert a considerable amount of catalytic effect through noncovalent π-stacking interactions.

In-vitro anti-sickling potential of baicalin and naringenin isolated from Oroxylum indicum and Citrus aurantium on human sickle red blood cells.

Sickle cell disease (SCD) is a rare inherited disorder in which red blood cells (RBCs) under oxidative stress have altered sickle shape resulting in clinical complications. In this study, a library of pure natural products were screened to see their effectiveness in preventing sickling induced in blood samples of SCA patients, ex-vivo. The results indicated that baicalin (1) and naringenin (2), reduced sickling by 46.03 and 37.48 percent, respectively, compared to positive control, 4-hydroxybenzoic acid (4-HBA), which inhibited RBC sickling by 56.87 percent. As a result of this screening, two compounds, baicalin (1) and naringenin (2), have been identified as potent sickling inhibitors. Study has clearly shown promising role of flavonoids for the management of SCD crisis for that not effective therapy is available. These phytochemicals or plant extracts can be explored further as an alternative anti-sickling remedy, owing to their high efficacy in the management of SCD crisis.

Ayurveda and in silico Approach: A Challenging Proficient Confluence for Better Development of Effective Traditional Medicine Spotlighting Network Pharmacology.

Coalescence of traditional medicine Ayurveda and in silico technology is a rigor for supplementary development of future-ready effective traditional medicine. Ayurveda is a popular traditional medicine in South Asia, emanating worldwide for the treatment of metabolic disorders and chronic illness. Techniques of in silico biology are not much explored for the investigation of a variety of bioactive phytochemicals of Ayurvedic herbs. Drug repurposing, reverse pharmacology, and polypharmacology in Ayurveda are areas in silico explorations that are needed to understand the rich repertoire of herbs, minerals, herbo-minerals, and assorted Ayurvedic formulations. This review emphasizes exploring the concept of Ayurveda with in silico approaches and the need for Ayurinformatics studies. It also provides an overview of in silico studies done on phytoconstituents of some important Ayurvedic plants, the utility of in silico studies in Ayurvedic phytoconstituents/formulations, limitations/challenges, and prospects of in silico studies in Ayurveda. This article discusses the convergence of in silico work, especially in the least explored field of Ayurveda. The focused coalesce of these two domains could present a predictive combinatorial platform to enhance translational research magnitude. In nutshell, it could provide new insight into an Ayurvedic drug discovery involving an in silico approach that could not only alleviate the process of traditional medicine research but also enhance its effectiveness in addressing health care.

Isovalent anion-induced electrochemical activity of doped Co3V2O8 for oxygen evolution reaction application.

The activity of an OER electrocatalyst is a strong function of the reaction kinetics at the active sites, which can be influenced by catalytic engineering (e.g., heterostructure, doping, and the addition of cocatalysts). Herein, we report the improved reaction kinetics of cobalt oxide for the OER via the addition of high valence vanadium and thereafter doping with sulphur (S-Co3V2O8). The addition of vanadium increases the oxygen vacancy while the doping of sulphur increases the electronic conductivity of the electrocatalyst. The synergic effect of the oxygen vacancy and electronic conductivity increases the activity of S-Co3V2O8. Furthermore, S-Co3V2O8 showed the least Tafel slope, which showed the activity enhancement towards the oxygen evolution reaction. Moreover, the underlying reaction mechanism is explored by electrochemical impedance spectroscopy, which reveals that the ratio of polarisation resistance to double-layer capacitance is minimum for S-Co3V2O8, indicating the highest activity.

Heterorhabditis and Photorhabdus Symbiosis: A Natural Mine of Bioactive Compounds.

Phylum Nematoda is of great economic importance. It has been a focused area for various research activities in distinct domains across the globe. Among nematodes, there is a group called entomopathogenic nematodes, which has two families that live in symbiotic association with bacteria of genus Xenorhabdus and Photorhabdus, respectively. With the passing years, researchers have isolated a wide array of bioactive compounds from these symbiotically associated nematodes. In this article, we are encapsulating bioactive compounds isolated from members of the family Heterorhabditidae inhabiting Photorhabdus in its gut. Isolated bioactive compounds have shown a wide range of biological activity against deadly pathogens to both plants as well as animals. Some compounds exhibit lethal effects against fungi, bacteria, protozoan, insects, cancerous cell lines, neuroinflammation, etc., with great potency. The main aim of this article is to collect and analyze the importance of nematode and its associated bacteria, isolated secondary metabolites, and their biomedical potential, which can serve as potential leads for further drug discovery.

Swarna Prashana - faith in the embrace of research.

Childhood needs diverse nutritional requirements. Poor appetite, lifestyle changes, and poor digestion affects child immunity and make them prone to diseases. Kaumarabhritya, a branch of Ayurveda which deals in child and adolescent health care, has a unique concept of Swarna Prashana (SP) to promote generalized immunity and intellect. SP is commonly recommended to children between 0 and 12 years of age and given as a general health promoter to improve intellect, digestion, strength, immunity, longevity, and complexion. Multiple benefits of SP are mentioned in different Samhitas which needs to be explored on scientific background. Authors have highlighted content variabilities, plausible mechanisms, research tasks and potentials, lacunae, and future prospects about SP. This manuscript is a spotlight on current social, clinical, marketing, and scientific information of Swarna Prashana. SP can be a cost-effective, safe, infrastructure compatible, and prevention-centric approach to improve children's overall health status and has the potential to serve as a positive health care program for children.

A Benchmark Study of Quantum Mechanics and Quantum Mechanics-Molecular Mechanics Methods for Carbocation Chemistry.

Carbocations play key roles in classical organic reactions and have also been implicated in several enzyme families. A hallmark of carbocation chemistry is multitudes of competing reaction pathways, and to be able to distinguish between pathways with quantum chemical calculations, it is necessary to approach chemical accuracy for relative energies between carbocations. Here, we present an extensive study of the performance of selected density functional theory (DFT) methods in describing the thermochemistry and kinetics of carbocations and their corresponding neutral alkenes both in the gas-phase and within a hybrid quantum mechanics-molecular mechanics (QM/MM) framework. The density functionals are benchmarked against accurate ab initio methods such as CBS-QB3 and DLPNO-CCSD(T). Based on the findings in the gas-phase calculations of carbocations and alkenes, the best functionals are chosen and tested further for non-covalent interactions in model systems using QM and QM/MM methods. We compute the interaction energies between a model carbocation/alkane and model π, dipole, and hydrophobic systems using DFT and QM(DFT)/MM and compare with DLPNO-CCSD(T). These latter model systems are representative of side chains of amino acids such as phenylalanine/tyrosine, tryptophan, asparagine/glutamine, serine/threonine, methionine, and other hydrophobic groups. The Lennard-Jones parameters of the QM atoms in QM(DFT)/MM calculations are modified to obtain an optimal fit with the QM energies. Finally, a selected carbocation reaction is studied in the gas phase and in implicit chloroform solvent using QM and in explicit chloroform solvent using QM/MM and umbrella sampling simulations. This study highlights the highest accuracy possible with selected density functionals and QM/MM methods but also some limitations in using QM/MM methods for carbocation systems.

Carotid Intima-media Thickness in Patients with Non-alcoholic Fatty Liver Disease Attending a Tertiary Care Center: A Descriptive Cross-sectional Study.

INTRODUCTION: Non-alcoholic fatty liver disease is fatty infiltration of the liver in the absence of other causes of steatosis. It is strongly associated with central adiposity, high body mass index, insulin resistance states, hypertension, hyperlipidemia which are features of metabolic syndrome. The objective of study is to find out the carotid intima-media thickness of non alcoholic fatty liver disease patients attending a tertiary care center. METHODS: This was a descriptive cross sectional study conducted at National Academy of Medical Sciences, Bir Hospital from July 2018 to June 2019 among 70 diagnosed cases of non alcoholic fatty liver disease based on ultrasound findings. Data collection was started after receiving ethical approval from Institutional Review Board of the Institute. Convenience sampling method was used. Data were entered using Microsoft Excel. The carotid intima-media thickness of both sides were measured by ultrasound. Statistical Package for Social Sciences version 20 was used for analysis. RESULTS: Out of 70 cases, the mean carotid intima-media thickness was 0.7140±0.1796mm on right and 0.7161±0.1828mm on left side. Among 70 cases 45 (64.3%) were Grade II non alcoholic fatty liver disease and 25 (35.7%) were Grade I. It was 0.5720±0.1275mm and 0.7929±0.1546mm in Grade I and II non alcoholic fatty liver disease cases respectively on right side whereas it was 0.5676±0.1259mm and 0.7987±0.1557mm respectively on left side. CONCLUSIONS: This study showed increased carotid intima-media thickness in non alcoholic fatty liver disease cases.

A rare case of Creutzfeldt-Jakob disease reported from Nepal.

Creutzfeldt-Jakob disease, though rare, should be considered in the clinical picture of rapidly progressive dementia and absence of verbal response as evident in our case despite the absence of typical radiological picture.

Benchmarking the Ability of Common Docking Programs to Correctly Reproduce and Score Binding Modes in SARS-CoV-2 Protease Mpro.

The coronavirus SARS-CoV-2 main protease, Mpro, is conserved among coronaviruses with no human homolog and has therefore attracted significant attention as an enzyme drug target for COVID-19. The number of studies targeting Mpro for in silico screening has grown rapidly, and it would be of great interest to know in advance how well docking methods can reproduce the correct ligand binding modes and rank these correctly. Clearly, current attempts at designing drugs targeting Mpro with the aid of computational docking would benefit from a priori knowledge of the ability of docking programs to predict correct binding modes and score these correctly. In the current work, we tested the ability of several leading docking programs, namely, Glide, DOCK, AutoDock, AutoDock Vina, FRED, and EnzyDock, to correctly identify and score the binding mode of Mpro ligands in 193 crystal structures. None of the codes were able to correctly identify the crystal structure binding mode (lowest energy pose with root-mean-square deviation < 2 Å) in more than 26% of the cases for noncovalently bound ligands (Glide: top performer), whereas for covalently bound ligands the top score was 45% (EnzyDock). These results suggest that one should perform in silico campaigns of Mpro with care and that more comprehensive strategies including ligand free energy perturbation might be necessary in conjunction with virtual screening and docking.

Fetus in Fetu in an Adult Female and Brief Review of Literature.

Fetus in fetu (FIF) is a very rare condition in which malformed fetus is found within the body of a living twin, most commonly within the retroperitoneum. It is a parasitic fetal twin of a diamniotic, monozygotic type. It should be differentiated from teratoma by the presence of organized vertebral column and appropriately arranged other organs or limbs around it. There is no such axial arrangement in teratoma, which has also got definite malignant potential. We report a case of FIF in a 21-year-old lady who presented late with nonspecific abdominal symptoms. Preoperative diagnosis of FIF in this case was made on computed tomography, and the patient underwent exploratory laparotomy with complete excision of mass. The excised mass in a sac was proven to be FIF on the basis of gross and histopathological examination. Surgical excision is the ideal treatment even teratoma being the differential diagnosis.

Correlation of Ultrasonographic Parameters with Serum Creatinine and Estimated Glomerular Filtration Rate in Patients with Echogenic Kidneys.

BACKGROUND: Ultrasonography is widely used to evaluate the kidney status. Serum creatinine and glomerular filtration rate assess the functional status of the kidney. This study tried to find the association between renal parameters in ultrasonography, serum creatinine and estimated glomerular filtration rate in patients with echogenic kidneys. METHODS: Study was done in 61 patients. Four sonographic renal parameters (renal echogenicity grade, renal length, cortical thickness, parenchymal thickness) were obtained from patients showing echogenic kidneys irrespective of cause during ultrasonography of abdomen. Glomerular filtration rate was calculated using Modified Diet in Renal Disease formula after obtaining patient's serum creatinine level. Sonographic renal parameters were compared with serum creatinine and estimated glomerular filtration rate using Pearson's correlation coefficient and one-way ANOVA tests. RESULTS: The study showed significant correlation of only renal echogenicity grade and parenchymal thickness with eGFR. However, all four sonographic renal parameters showed significant correlation with serum creatinine level. Renal echogenicity grading had strongest correlation with both serum creatinine (r=0.571, p=0.000) and estimated glomerular filtration rate (r= -0.349, p=0.006). Mean serum creatinine (in mg/dL) ± standard deviation was 1.9(±1.5), 4.0(±3.7), 5.8(±3.7), and 15.4(±5.3) for grade I, II, III, and IV echogenic kidneys respectively. Similarly, mean eGFR (in ml/min/1.73m2) ± standard deviation was 50.2(±22.9), 35.9(±40), 15.7(±13.4), and 3.4(±1.1) for Grade I, II, III, and IV echogenic kidneys respectively. CONCLUSIONS: Renal echogenicity is a better sonographic parameter that correlated well with both eGFR and serum creatinine. Renal ultrasound should be routinely used for early diagnosis, grading and monitoring of kidney disease.