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The process of heme binding to a protein is prevalent in almost all forms of life to control many important biological properties, such as O 2 -binding, electron transfer, gas sensing or to build catalytic power. In these cases, heme typically binds tightly (irreversibly) to a protein in a discrete heme binding pocket, with one or two heme ligands provided most commonly to the heme iron by His, Cys or Tyr residues. Heme binding can also be used as a regulatory mechanism, for example in transcriptional regulation or ion channel control. When used as a regulator, heme binds more weakly, with different heme ligations and without the need for a discrete heme pocket. This makes the characterization of heme regulatory proteins difficult, and new approaches are needed to predict and understand the heme-protein interactions. We apply a modified version of the ProFunc bioinformatics tool to identify heme-binding sites in a test set of heme-dependent regulatory proteins taken from the Protein Data Bank and AlphaFold models. The potential heme binding sites identified can be easily visualized in PyMol and, if necessary, optimized with RosettaDOCK. We demonstrate that the methodology can be used to identify heme-binding sites in proteins, including in cases where there is no crystal structure available, but the methodology is more accurate when the quality of the structural information is high. The ProFunc tool, with the modification used in this work, is publicly available at https://www.ebi.ac.uk/thornton-srv/databases/profunc and can be readily adopted for the examination of new heme binding targets., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This Letter presents the measurement of near-side associated per-trigger yields, denoted ridge yields, from the analysis of angular correlations of charged hadrons in proton-proton collisions at sqrt[s]=13  TeV. Long-range ridge yields are extracted for pairs of charged particles with a pseudorapidity difference of 1.4<|Δη|<1.8 and a transverse momentum of 1

Background and objective Anemia, particularly iron deficiency anemia (IDA), presents a significant global health challenge, particularly among children under the age of five years in developing nations. Concurrently, febrile convulsions (FC) affect up to 5% of neurologically healthy children aged 6-60 months, causing considerable distress among parents. There is a suggested correlation between fever and iron deficiency, which may exacerbate neurological risks, potentially lowering seizure thresholds and increasing the risk of FC. However, studies investigating the relationship between IDA and FC have shown conflicting results. In light of this, this study aimed to explore this relationship among children aged 6-60 months in Eastern India, an area where this association has yet to be thoroughly investigated. Materials and methods The case-control study included children aged 6-60 months. The cases consisted of children presenting with FC, while controls comprised children in the same age group presenting with febrile illness but without seizures. Informed consent was obtained, a detailed history was taken, and clinical examinations were conducted for both groups. Blood investigations were performed to diagnose IDA according to WHO criteria: hemoglobin <11 gm/dl with the classical triad of low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH), and low mean corpuscular hemoglobin concentration (MCHC) for age. Data analysis was performed using the R-based software Jamovi 2.4.8. with appropriate statistical tests. Results We included 81 cases and 80 controls. The study found a statistically significant association between IDA and FC with an odds ratio (OR) of 2.25 [95% confidence interval (CI): 1.03-4.91; p=0.039]. Additionally, the study revealed that hemoglobin levels, MCH, MCV, and MCHC were lower among cases compared to controls, while the red cell distribution width (RDW) was higher. Both these findings regarding RBC indices were statistically significant (p<0.05). Conclusions Our findings indicate a statistically significant association between IDA and FC among children under five years of age. Implementing measures to prevent IDA and strengthening existing strategies may help alleviate the burden of FC in this vulnerable population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mandal et al.)

The first measurement of the cross section for incoherent photonuclear production of J/ψ vector mesons as a function of the Mandelstam |t| variable is presented. The measurement was carried out with the ALICE detector at midrapidity, |y|<0.8, using ultraperipheral collisions of Pb nuclei at a center-of-mass energy per nucleon pair of sqrt[s&#95;{NN}]=5.02  TeV. This rapidity interval corresponds to a Bjorken-x range (0.3-1.4)×10^{-3}. Cross sections are given in five |t| intervals in the range 0.04<|t|<1  GeV^{2} and compared to the predictions by different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a |t| dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data.

This work reports the synthesis of a dual functional 2D framework, {[Zn 2 (4-tpom) 2 (oxdz) 2 ]·4H 2 O} n ( 1 ), at room temperature, where a bent dicarboxylate, oxdz 2- (4,4'-(1,3,4-oxadiazole-2,5-diyl)dibenzoate), and a neutral flexible N-donor linker, 4-tpom (tetrakis(4-pyridyloxymethylene)methane), are utilized. Its single-crystal X-ray analysis indicated a 2-fold interpenetrated 2D framework having tetracoordinated Zn(II) centers and dangling pyridyl groups. Its further characterization was carried out with elemental microanalysis, FTIR spectroscopy, TG analysis, and powder X-ray diffraction. The tetracoordinated Zn(II) centers as active Lewis acidic sites and the N atoms of 4-tpom as Lewis basic sites in 1 are explored for its functioning as a heterogeneous catalyst in two important reactions, (i) cycloaddition of CO 2 with various epoxides and (ii) cyanosilylation reaction under solvent-free conditions. We could successfully show the cycloaddition of styrene oxide with CO 2 (99% conversion) under balloon pressure with low catalyst (0.2-0.3 mol %) and cocatalyst (0.5-0.75 mol %) loadings, which is otherwise difficult to achieve. It was observed that all the substrates (aromatic and aliphatic), irrespective of their sizes, showed conversion percentage >99%. In the cyanosilylation reaction, a conversion of 96% was obtained with 1.5 mol % of 1 at room temperature for 12 h. This framework emerged as an excellent recyclable catalyst for both the reactions.

5-Methylcytosine methyltransferases (m 5 C MTases) are known to be involved in the modification of RNA. Although these enzymes have been relatively well characterized in bacteria and eukarya, a complete understanding of the archaeal counterparts is lacking. In this study, the identification and characterization of archaeal RNA m 5 C MTases were performed. As a case study, a hyperthermophilic archaeon, Pyrococcus horikoshii OT3, which possesses five putative RNA m 5 C MTases, was chosen. Among the five putative RNA m 5 C MTases, two proteins (PH0851 and PH1991) have been characterized as homologs of a bacterial rRNA MTase (RsmB) and eukaryal tRNA MTase (NSUN6), respectively. The in-depth characterization of the remaining three putative RNA m 5 C MTases (PH1078, PH1374, and PH1537) in this study suggests the presence of the signature architecture and catalytic residues plausibly involved in the binding of their cognate RNA substrates. Additionally, the results also suggest the existence of two RsmB-like proteins (PH0851 and PH1078) belonging to the same subfamily IV of m 5 C RNA MTase. However, the proteins PH1374 and PH1537 belong to the same subfamily V but bind to different substrates, rRNA and tRNA, respectively. The findings further indicate that archaeal RNA m 5 C MTases link those from bacteria and eukarya.Communicated by Ramaswamy H. Sarma.

Background: Neovascular glaucoma (NVG) is a secondary glaucoma with a poor visual prognosis. Trabeculectomy with antifibrotic agents, glaucoma drainage devices (GDDs), and cyclo-destructive procedures are recommended in patients who are refractory to medical management. However, due to the poor success rate of conventional trabeculectomy and the higher cost of GDDs, alternative procedures need to be looked at., Purpose: To compare the surgical outcomes and economic aspects of a newly developed polypropylene suture bed-based modified trabeculectomy to Ahmed glaucoma valve (AGV) implantation for NVG., Methods: It was a prospective interventional study conducted at a tertiary care center between 2018 and 2020. Consecutive patients with NVG with a minimum follow-up of 18 months were included. Surgical outcomes are mainly based on intraocular pressure (IOP) control and the cost of surgery., Results: Sixty eyes were included out of which 40 (60.6%) underwent modified trabeculectomy and 20 (33.7%) underwent AGV. At the final follow-up, no significant difference (P < 0.05) was found between the surgical outcomes of both groups. The complete success rate (IOP < 21 mm Hg without antiglaucoma medications) was 60 and 65% while the qualified success rate (IOP < 21 mm Hg with antiglaucoma medications) was 30 and 25% in modified trabeculectomy and AGV groups, respectively, at final follow-up. The cost of surgery was significantly higher in the AGV group (P < 0.0001)., Conclusion: Modified trabeculectomy as described might be a better alternative for NVG eyes., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Recent research has uncovered a promising approach to addressing the growing global health concern of obesity and related disorders. The inhibition of inositol hexakisphosphate kinase 1 (IP6K1) has emerged as a potential therapeutic strategy. This study employs multiple ligand-based in silico modeling techniques to investigate the structural requirements for benzisoxazole derivatives as IP6K1 inhibitors. Firstly, we developed linear 2D Quantitative Structure-Activity Relationship (2D-QSAR) models to ensure both their mechanistic interpretability and predictive accuracy. Then, ligand-based pharmacophore modeling was performed to identify the essential features responsible for the compounds' high activity. To gain insights into the 3D requirements for enhanced potency against the IP6K1 enzyme, we employed multiple alignment techniques to set up 3D-QSAR models. Given the absence of an available X-ray crystal structure for IP6K1, a reliable homology model for the enzyme was developed and structurally validated in order to perform structure-based analyses on the selected dataset compounds. Finally, molecular dynamic simulations, using the docked poses of these compounds, provided further insights. Our findings consistently supported the mechanistic interpretations derived from both ligand-based and structure-based analyses. This study offers valuable guidance on the design of novel IP6K1 inhibitors. Importantly, our work exclusively relies on non-commercial software packages, ensuring accessibility for reproducing the reported models.

We designed a trigonal symmetric imine-linked covalent organic framework (COF), TFPC-DAB, with control over the angularity of the building units, where a bent C2-symmetric diamine, such as 1,3-diaminobenzene (1,3-DAB or DAB), with an exo-angle of 120° was used instead of those with an exo-angle of 180°, in combination with a C3-symmetric trialdehyde, such as tri(4-formylphenoxy)cyanurate (TFPC). Its synthesis was accomplished by reacting the building units in a mixture of mesitylene/dioxane/6 M acetic acid under solvothermal conditions. The phase purity, thermal stability, and porosity of TFPC-DAB were established by various analytical techniques. Utilizing the Density Functional Tight Binding (DFTB+) simulation and Pawley refinement, the best fit of the small angle x-ray pattern was found to have an AA stacking of TFPC-DAB in the trigonal space group P3 with low refinement parameters. Such smart materials are in huge demand to detect hazardous corrosive chemicals, such as HCl and NH3. The dual features of electron deficient π-acidic triazine moiety and heteroatoms (N/O) from TFPC and electron rich phenyl units from DAB embodied in the framework enhance its luminescent property and thereby make it suitable for solvent-based HCl and NH3 sensing. The detection limits for HCl and NH3 in methanol were found to be 14 and 82 ppb, respectively. The effect of solvent polarity on the sensing studies was observed with much lower detection limits in dioxane: 2.5 and 11 ppb for HCl and NH3, respectively. A detailed theoretical calculation using density functional theory and configurational bias Monte Carlo modules was conducted for understanding interactions between the COF and HCl or NH3 analytes., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Tumor diseases remain among the world's primary causes of death despite substantial advances in cancer diagnosis and treatment. The adverse chemotherapy problems and sensitivity towards drugs for some cancer types are among the most promising challenges in modern treatment. Finding new anti-cancer agents and drugs is, therefore, essential. A significant class of biologically active substances and prospective medications against cancer is comprised of bacterial proteins and peptides. Among these bacterial peptides, some of them, such as anti-cancer antibiotics and many toxins like diphtheria are widely being used in the treatment of cancer. In contrast, the remaining bacterial peptides are either in clinical trials or under research in vitro studies. This study includes the most recent information on the characteristics and mechanism of action of the bacterial peptides that have anti-cancer activities, some of which are now being employed in cancer therapy while some are still undergoing research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In India, the incidence of mucormycosis reached high levels during 2021-2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March-July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease's clinical progression and help frame standard treatment guidelines., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: People of all nationalities and social classes are now affected by the growing issue of hypertension. Over time, there has been a consistent rise in the fatality rate. A range of therapeutic compounds, on the other hand, are often used to handle hypertension., Objectives: The objectives of this study are first to design potential antihypertensive drugs based on the DHP scaffold, secondly, to analyse drug-likeness properties of the ligands and investigate their molecular mechanisms of binding to the model protein Cav1.2 and finally to synthesise the best ligand., Materials and Methods: Due to the lack of 3D structures for human Cav1.2, the protein structure was modelled using a homology modelling approach. A protein-ligand complex's strength and binding interaction were investigated using molecular docking and molecular dynamics techniques. DFT-based electronic properties of the ligand were calculated using the M06-2X/ def2- TZVP level of theory. The SwissADME website was used to study the ADMET properties., Results: In this study, a series of DHP compounds (19 compounds) were properly designed to act as calcium channel blockers. Among these compounds, compound 16 showed excellent binding scores (-11.6 kcal/mol). This compound was synthesised with good yield and characterised. To assess the structural features of the synthesised molecule quantum chemical calculations were performed., Conclusion: Based on molecular docking, molecular dynamics simulations, and drug-likeness properties of compound 16 can be used as a potential calcium channel blocker., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present study aimed to evaluate Cassia fistula seed galactomannan (CFSG) as a tablet-binder in the formulation of a monolithic matrix tablet using diclofenac sodium as a model drug. Initially, CFSG was extracted and purified from the seeds of the Cassia fistula tree and then screened for phytochemicals. Native CFSG was characterized with polysaccharide content determination, monosaccharide composition analysis, elemental analysis, FTIR, solid-state 13 C NMR, molecular weight, zeta potential, DSC, TGA-DTA, XRD, viscosity, pH and surface tension, rheology, SEM and acute oral toxicity study. Prior to formulation, the drug-CFSG compatibility was checked by FTIR, DSC, and XRD. Diclofenac sodium-loaded granules were prepared by the wet granulation method and evaluated for various granule properties. Finally, granules were compressed into tablets and evaluated for binding and other tablet properties. The granules showed to have optimum micromeritic properties. Tablet hardness and friability were found to be approximately 7 kg/m 2 and 0.3 %, respectively, which substantiate the excellent binding capacity of CFSG. Other tablet properties were also found to be within the Pharmacopoeial compliance limit. The tablets with a minimum concentration of CFSG (2.5%w/w) as binder showed appreciable mechanical strength and faster drug release, which ratifies CFSG as an alternative tablet binder., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Noncommunicable diseases have emerged as a major cause of morbidity and mortality worldwide among which the majority of the deaths are caused by cardiovascular diseases. Estimating the risk of cardiovascular diseases helps eliminate the risk factors and prevent developing cardiovascular diseases in the future. The World Health Organization in association with the International Society of Hypertension has developed risk charts for the estimation of 10-year risk for cardiovascular diseases. This study aimed to estimate 10-year cardiovascular risk in the Nepalese population using nonlaboratory-based charts., Methods: A hospital-based cross-sectional study was conducted among 314 adults aged 40-74 years visiting the outpatient departments of Shishuwa Hospital in western Nepal. Systematic random sampling was used to select the participants. Questionnaire-guided short interviews, physical examination, and anthropometric measurements were done. The χ 2 test was used to test the significance and a p  < 0.05 was considered statistically significant., Results: As per the risk estimation charts, high cardiovascular risk (20%-30%) was seen in 6.1% of total participants and moderate cardiovascular risk (10%-20%) was found in 29% of participants. The moderate-high risk was significantly higher among male participants compared to females ( p  < 0.01). Of all the participants, 22.0% were current smokers, 17.2% were alcohol users, 61.1% were hypertensive, and 35.7% were diabetics. Smoking tobacco, alcohol use, and hypertension were significantly more prevalent among the male participants. ( p  < 0.01) Adults in the 50-59 years age group had a significantly high prevalence of hypertension ( p  < 0.01), diabetes ( p  = 0.02), and alcohol abuse ( p  = 0.01)., Conclusion: This study shows high cardiovascular risk among adult population in western Nepal. The 10-year cardiovascular risk score and risk factors were significantly higher among males than females. There seems to be a prompt necessity of health promotion interventions to reduce cardiovascular risk factors and prevent the burden of cardiovascular diseases in Nepal., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Introduction: Tofacitinib has emerged as a therapeutic option for axial spondyloarthritis (axSpA) following successful clinical trials. The evidence on the efficacy of tofacitinib generics in the management of axSpA is limited. In India, the usage of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is commonplace in the management of axSpA. Our primary aim was to identify the csDMARD and non-steroidal anti-inflammatory drug (NSAID)-sparing role of tofacitinib generics in an axSpA population., Methods: This was a retrospective study in a real-world clinical setting. Data from nine rheumatology centers across India were analyzed for 168 patients with active axSpA who were initiated on generic tofacitinib 5 mg twice daily in conjunction with csDMARDs and NSAIDs, over a duration of six months. Our primary outcome was to evaluate the csDMARD and NSAID-sparing effect of tofacitinib generics, while the secondary outcome assessed safety profiles and efficacy at six months., Results: The median Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR) score of the study population was 3.91 (3.26, 4.56). Alongside tofacitinib generics, 121 (72%) patients were co-administered csDMARDs (methotrexate/sulfasalazine/both), and 90 (53.6%) patients were co-administered NSAIDs. The csDMARD, NSAID, and combined csDMARD + NSAID-sparing effects of tofacitinib generics were seen in 85 (50.6%), 156 (92.9%), and 81 (48.2%) patients, respectively. Adverse events were mild and well-tolerated. At six months, 124 (57.9%) patients had attained clinically important improvement in ASDAS ESR score, and the median decrease in ASDAS ESR score was 2.02 (1.18, 2.96)., Conclusion: This real-world study provides evidence supporting the csDMARD and NSAID-sparing ability of tofacitinib generics in the treatment of axSpA. Tofacitinib generics displayed a good safety profile and showed signals of efficacy as well., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ganapati et al.)

Temperature downshifts are the gold standard when setting up control strategies for mammalian cell culture processes. These shifts are performed to prolong production phases and attain heightened levels of productivity. For the development of biosimilars, however, the bottleneck is in achieving a prespecified product quality. In a late-stage development project, we investigated the impact of temperature shifts and other process parameters with the aim of optimizing the glycosylation profile of a monoclonal antibody (mAb). We applied a design of experiments approach on a 3 L scale. The optimal glycosylation profile was achieved when performing a temperature upshift from 35.8 °C to 37 °C. Total afucosylated glycan (TAF) decreased by 1.2%, and galactosylated glycan species (GAL) increased by up to 4.5%. The optimized control strategy was then successfully taken to the manufacturing scale (1000 L). By testing two sets of set points at the manufacturing scale, we demonstrated that the statistical models predicting TAF and GAL trained with small-scale data are representative of the manufacturing scale. We hope this study encourages researchers to widen the screening ranges in process development and investigate whether temperature upshifts are also beneficial for other mAbs.

A Pd(II)-catalyzed strategy for the diastereo- and regioselective (hetero)arylation of unactivated C(sp 3 )-H bonds in bile acids is accomplished with aryl and heteroaryl iodides under solvent-free conditions using the 8-aminoquinoline auxiliary as a directing group. This methodology demonstrated excellent functional group tolerance with respect to aryl/heteroaryl iodides on O -protected N -(quinolin-8-yl)cholyl/deoxycholyl amides to afford β-C(sp 3 )-H (hetero)arylated products in good-to-excellent yields. Moreover, the 8-aminoquinoline (AQ) auxiliary can easily be removed to obtain modified bile acids.

Generation of clean energy in a viable manner demands efficient and sustainable catalysts. One prospective method of clean energy generation is the electrochemical hydrogen evolution reaction (HER). Over the years, various transition metal-based complexes/polymeric organic materials were utilized in HER. However, the use of a redox-active small organic molecule as a catalyst for HER has not been explored well. The requirements of a strongly acidic solution, very high overpotential, and stability under acidic conditions pose several challenges for applying organic electrocatalysts for HER. Considering these challenges, herein, we demonstrated an NADP + -like organic system (NADP + = nicotinamide adenine dinucleotide phosphate), a bis-imidazolium-fused heterohelicene, which acts as a catalyst for HER with mild acid (acetic acid) as a proton source at moderate overpotential. The unique structural backbone of this dicationic heterohelicene allowed to exploit the NADP + /NADPH-type (NADPH = reduced nicotinamide adenine dinucleotide phosphate) hydride transfer-based redox cycle efficiently under the applied conditions, where the NADPH-like hydride intermediate transfers the hydride to the proton of the mild acid to generate H 2 . The Faradaic efficiency and turnover number for the present HER were achieved up to 85 ± 5% and 50 ± 3, respectively. In addition, the maximum turnover frequency, TOF max , value of 410 s -1 was observed, which is around 400 times that obtained for the existing reported NADP + -like organic compounds used as catalysts for HER. Thorough mechanistic studies were conducted experimentally and computationally to establish a plausible catalytic cycle. This advancement could help in designing efficient organic electrocatalysts for HER from a mild proton source.

Pullulan is a commercially available exopolymer biosynthesized by Aureobasidium pullulans supplemented with nitrogen, carbon and other vital components through submerged and solid-state fermentation. These nutrients are very expensive and it raises the cost for the production of pullulan. Hence, the need of alternative cost-effective raw materials for its production is a prerequisite. Owing to its unique physicochemical features, pullulan has various applications in the food, pharmacological, and biomedical domains. Food industrial wastes generate a considerable number of by-products which accumulates and has a negative influence on the environment. These by-products are made up of proteins, carbohydrates, and other components, can be employed as substrates for the production of pullulan. The present review briefs on the pullulan production using food processing waste and by-products and the elements that impact it. It provides an insight into versatile applications of pullulan in food industries. Various challenges and future prospects in the field of research on pullulan production have been uncovered., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Association of Food Scientists & Technologists (India) 2022.)

Background and Aim: Novel nature of the viral pathogen SARS-CoV-2 and the absence of standard drugs for treatment, have been a major challenge to combat this deadly infection. Natural products offer safe and effective remedy, for which traditional ethnic medicine can provide leads. An indigenous poly-herbal formulation, Kabasura Kudineer from Siddha system of medicine was evaluated here using a combination of computational approaches, to identify potential inhibitors against two anti-SARS-CoV-2 targets - post-fusion Spike protein (structural protein) and main protease (Mpro, non-structural protein)., Experimental Procedure: We docked 32 phytochemicals from the poly-herbal formulation against viral post-fusion Spike glycoprotein and Mpro followed by molecular dynamics using Schrodinger software. Drug-likeness analysis was performed using machine learning (ML) approach and pkCSM., Results: The binding affinity of the phytochemicals in Kabasura Kudineer revealed the following top-five bioactives: Quercetin > Luteolin > Chrysoeriol > 5-Hydroxy-7,8-Dimethoxyflavone > Scutellarein against Mpro target, and Gallic acid > Piperlonguminine > Chrysoeriol > Elemol > Piperine against post-fusion Spike protein target. Quercetin and Gallic acid exhibited binding stability in complexation with their respective viral-targets and favourable free energy change as revealed by the molecular dynamics simulations and MM-PBSA analysis. In silico predicted pharmacokinetic profiling of these ligands revealed appropriate drug-likeness properties., Conclusion: These outcomes provide: (a) potential mechanism for the anti-viral efficacy of the indigenous Siddha formulation, targeting Mpro and post-fusion Spike protein (b) top bioactive lead-molecules that may be developed as natural product-based anti-viral pharmacotherapy and their pleiotropic protective effects may be leveraged to manage co-morbidities associated with COVID-19., Competing Interests: The authors declare no conflict of interest., (© 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Herein, we report the first catalytic methylation of primary amides using CO 2 as a C1 source. A bicyclic (alkyl)(amino)carbene (BICAAC) exhibits dual role by activating both primary amide and CO 2 to carry out this catalytic transformation which enables the formation of a new C-N bond in the presence of pinacolborane. This protocol was applicable to a wide range of substrate scopes, including aromatic, heteroaromatic, and aliphatic amides. We successfully used this procedure in the diversification of drug and bioactive molecules. Moreover, this method was explored for isotope labelling using 13 CO 2 for a few biologically important molecules. A detailed study of the mechanism was carried out with the help of spectroscopic studies and DFT calculations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Molecules with solid state luminescence and mechanochromic luminescence properties have attracted immense interest owing to their potential application in the areas of organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs), optoelectronic devices, fluorescence switches, mechano-sensors and data storage. Herein we report a convenient two step synthetic protocol to obtain a couple of luminescent molecules. Using these, a comparative study has been performed to showcase the importance of the weak π⋯π interactions to observe the aggregation induced emission (AIE) and solid-state mechanochromic luminescence. The most fascinating part of this report is to observe the switchable fluorescent dark and bright states of the solid AIEgen. We have also demonstrated the use of the AIEgen to detect volatile organic compounds.

Biomimetic NAD(P)H-type organic hydride donors have recently been advocated as potential candidates to act as metal-free catalysts for fuel-forming reactions such as the reduction of CO 2 to formic acid and methanol, similar to the natural photosynthesis process of fixing CO 2 into carbohydrates. Although these artificial synthetic organic hydrides are extensively used in organic reduction chemistry in a stoichiometric manner, translating them into catalysts has been challenging due to problems associated with the regeneration of these hydride species under applied reaction conditions. A recent discovery of the possibility of their regeneration under electrochemical conditions via a proton-coupled electron-transfer pathway triggered intense research to accomplish their catalytic use in electrochemical CO 2 reduction reactions (eCO 2 RR). However, success is yet to be realized to term them as "true" catalysts, as the typical turnover numbers (TONs) of the eCO 2 RR processes on inert electrodes for the production of formic acid and/or methanol reported so far are still in the order of 10 -3 -10 -2 ; thus, sub-stoichiometric only! Herein, we report a novel class of structurally engineered heterohelicene-based organic hydride donor with a proof-of-principle demonstration of catalytic electrochemical CO 2 reduction reaction showing a significantly improved activity with more than stoichiometric turnover featuring a 100-1000-fold enhancement of the existing TON values. Mechanistic investigations suggested the critical role of the two cationic imidazolium motifs along with the extensive π-conjugation present in the backbone of the heterohelicene molecules in accessing and stabilizing various radical species involved in the generation and transfer of hydride, via multielectron-transfer steps in the electrochemical process.

Purpose: To compare surgical and functional outcomes, safety, efficacy and cost of silicone plate vs. autogenous auricular cartilage (AAC) as alternate material to tarsal plate for upper eyelid reconstruction after excision of malignant tumor. Methods: A prospective, comparative, interventional study of over 3 years was conducted on two groups of twenty patients each. All the patients had undergone the Modified Cutler Beard procedure with AAC being used as tarsal substitute in one group and a novel silicone plate in the other. Post-operative MRD 1, LPS action, Central Lid Thickness, and Lid contour were recorded at one week, one month and six months follow-up. Results: The pre-operative MRD 1 in the silicone plate and AAC group was -2.95 ± 1.19 mm and -3.05 ± 1(1).05 mm, post-operative in the silicone plate group 3.8 ± 0.4 mm, and in the AAC group, 3.8 ± 0.41 mm. The pre-operative LPS action in the silicone plate and AAC group was 1.2 ± 1.1 mm and 1.0 ± 0.9 mm and post-operative it was 13.8 ± 0.4 mm for the silicone plate group and 13.7 ± 0.4 mm for the AAC group. The post-operative lid thickness for the silicone plate group was 4.4 ± 0.17 mm and for the AAC group it was 4.4 ± 0.08 mm. Conclusion: The cosmetic outcome in terms of lid contour maintenance is better in the silicone plate group, in which it markedly reduces the surgical time, provides earlier rehabilitation, and eliminates disease transmission. Harvesting of AAC is a skillful and time-consuming procedure and adds to the post-operative morbidity due to the presence of a second surgical site. The low manufacturing cost of silicone plate as opposed to other allogenic and synthetic tarsal substitutes makes it readily available to resource limited populations. The silicone plate is reckoned to become the material of choice as tarsal substitute in the future. Abbreviations: AAC = Autogenous auricular cartilage, MRD-1 = Margin reflex distance-1, LPS = levator palpebrae superioris, PFH = palpebral fissure height., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Introduction: Phenolic phytochemicals are known for antioxidant-mediated pharmacological effects in various diseases (diabetes, cancer, CVDs, obesity, inflammatory and neurodegenerative disorders). However, individual compounds may not exert the same biological potency as in combination with other phytochemicals. Cyamopsis tetragonoloba (Guar), an underutilized semi-arid legume which has been used as a traditional food in Rajasthan (India), is also a source of the important industrial product guar gum. However, studies on its biological activity, like antioxidant, are limited., Methods: We tested the effect of C. tetragonoloba seed extract to enhance the antioxidant activity of well-known dietary flavonoids (quercetin, kaempferol, luteolin, myricetin, and catechin) and non-flavonoid phenolics (caffeic acid, ellagic acid, taxifolin, epigallocatechin gallate (EGCG), and chlorogenic acid) using DPPH radical scavenging assay. The most synergistic combination was further validated for its cytoprotective and anti-lipid peroxidative effects in in vitro cell culture system, at different concentrations of the extract. LC-MS analysis of purified guar extract was also performed., Results and Discussion: In most cases, we observed synergy at lower concentrations of the seed extract (0.5-1 mg/ml). The extract concentration of 0.5 mg/ml enhanced the antioxidant activity of Epigallocatechin gallate (20 µg/ml) by 2.07-folds, implicating its potential to act as an antioxidant activity enhancer. This synergistic seed extract-EGCG combination diminished the oxidative stress nearly by double-fold when compared with individual phytochemical treatments in in vitro cell culture. LC-MS analysis of the purified guar extract revealed some previously unreported metabolites, including catechin hydrate, myricetin-3-galactoside, gossypetin-8-glucoside, and puerarin (daidzein-8-C-glucoside) which possibly explains its antioxidant enhancer effect. The outcomes of this study could be used for development of effective nutraceutical/dietary supplements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Joshi, Mandal, Puri, Asati, Deepa and Sharma.)

The present study demonstrates the first transition-metal-free catalytic C-alkylation via a borrowing hydrogen pathway for the α-alkylation of ketone, synthesis of substituted quinoline, and 9-monoalkylation of fluorene. With applications on diversification of biologically active molecules and gram-scale synthesis, a preliminary investigation of the reaction mechanism has been carried out, suggesting a radical-mediated borrowing hydrogen pathway.

The vulnerability of human health is amplified in recent times with global increase in non-communicable diseases (due to lifestyle changes and environmental insults) and infectious diseases (caused by newer pathogens and drug-resistance strains). Clinical management of diseases is further complicated by disease severity caused by other comorbid factors. Drug-based therapy may not be the sole approach, particularly in scenarios like the COVID-19 pandemic, where there is no specific drug against SARS-CoV-2. Nutritional interventions are significant in armouring human populations in disease prevention, and as adjunctive therapy for disease alleviation. Amidst ongoing clinical trials to determine the efficacy of Vit. D against infections and associated complications, this review examines the pleiotropic benefits of nutritional adequacy of vitamin D (Vit. D) in combating viral infections (COVID-19), its severity and complications due to co-morbidities (obesity, diabetes, stroke and Kawasaki disease), based on research findings and clinical studies. Supplements of Vit. D in combination with other nutrients, and drugs, are suggested as promising preventive-health and adjunct-treatment strategies in the clinical management of viral infections with metabolic comorbidities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca 2+ -dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca 2+ -dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety., (© 2022 John Wiley & Sons Ltd.)

Background: Every year, drug poisoning is the most prevalent reason for referring patients to medical centers. This study aimed to evaluation of morphine, methadone, digoxin, and dronabinol poisoning in Shahid Mostafa Khomeini Hospital in Ilam., Methods: In this In this Cross-sectional study, patient samples suspected of morphine, methadone, digoxin, and dronabinol poisoning referred to the toxicology laboratory of Ilam University of Medical Sciences were analyzed using the HPLC method, and the results were analysed using SPSS software., Results: Results showed that the percentage of drug use is greater in men than in women. The highest percentage of morphine and methadone poisonings were detected in those under the age of 40, whereas the highest percentage of digoxin poisonings were recorded in those over the age of 80. As a result, the average age of digoxin users was substantially greater in men than in women. Methadone consumers showed significantly greater blood levels than others. In addition, there was a significant difference (P<0.01) in blood levels between men and women who used morphine., Conclusion: In general, it is important to understand the status of drug poisoning with drugs such as morphine, methadone, digoxin, and dronabinol, as well as the prognosis associated with the treatment process of such poisoning., Competing Interests: The authors declare that there is no conflict of interest.

Multifunctional metal-organic frameworks (MOFs) rely on the properties of metal centers (nodes) and/or linkers (struts) for their diverse applications in the emerging field of research. Currently, there is a huge demand for MOF materials in the field of capture/fixation/sensing of air pollutants, harmful chemical effluents, and nuclear waste. However, it is a challenging task to utilize one MOF for providing remedies to all these issues. On the basis of our current research activities, we have identified that an oxadiazole moiety-a five-membered ring with two different heteroatoms (O and N)-in a carboxylate linker can be the key to generating such MOF materials for its (a) inherent polarizable nature and molecular docking ability and (b) photoluminescence properties. In this work, we report a 3D MOF {[Co 2 (oxdz) 2 (tpbn)(H 2 O) 2 ]·4H 2 O} n ( 1 ), self-assembled at room temperature from a three-component reaction, with an oxadiazole moiety (where H 2 oxdz = 4,4'-(1,3,4-oxadiazole-2,5-diyl)dibenzoic acid and tpbn = N,N',N,"N″'-tetrakis(2-pyridylmethyl)-1,4-diaminobutane). The inherent polarizable nature of the oxadiazole moiety in 1 has been efficiently exploited for (i) multimedia iodine capture and (ii) fixation of CO 2 under solvent-free and ambient conditions. On the other hand, the luminescent nature of the framework is found to be an efficient, highly preferred turn-on sensor for the ultra-fast detection of ketones with a limit as low as parts-per-trillion (mesitylene oxide: 447 ppt; cycloheptanone: 4.7 ppb; cyclohexanone: 17.2 ppb; acetylacetone: 18 ppb).

Serendipitous and expedite transformation of 1-aryl- and 2-aryl-1,2-dihydro-3 H -indazol-3-ones to 1,2-di(hetero)aryl- and 2,3-di(hetero)aryl-2,3-dihydroquinazolin-4(1 H )-ones, respectively, was achieved in high efficiency by reacting them with aldehydic N -tosylhydrazones. The protocol proceeded through a cascade process involving base-mediated Pd-carbenoid generation by the decomposition of N -tosylhydrazones, nucleophilic attack of indazolone on the Pd-carbenoid complex, and intramolecular ring expansion via N-N bond cleavage. The utility of the strategy is demonstrated toward the synthesis of bioactive NPS 53574, a calcium receptor antagonist.

Solid-state radical generation is an attractive but underutilized methodology in the catalytic strong bond activation process, such as the aryl-halide bond. Traditionally, such a process of strong bond activation relied upon the use of transition metal complexes or strongly reducing photocatalysts in organic solvents. The generation of the aryl radical from aryl halides in the absence of transition-metal or external stimuli, such as light or cathodic current, remains an elusive process. In this study, we describe a reduced organic hydrocarbon, which can act as a super reductant in the solid state to activate strong bonds by solid-state single electron transfer (SSSET) under the influence of mechanical energy leading to a catalytic strategy based on the mechano-SSSET or mechanoredox process. Here, we investigate the solid-state synthesis of the super electron donor phenalenyl anion in a ball mill and its application as an active catalyst in strong bond (aryl halide) activation. Aryl radicals generated from aryl halides by employing this strategy are competent for various carbon-carbon bond-forming reactions under solvent-free and transition metal-free conditions. We illustrate this approach for partially soluble or insoluble polyaromatic arenes in accomplishing solid-solid C-C cross-coupling catalysis, which is otherwise difficult to achieve by traditional methods using solvents., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

A Mn I catalyst featuring redox-active tridentate phenalenyl (PLY) ligand has been used for catalytic N-formylation of secondary amides and lactams under 1 atm CO 2 as a C 1 source at room temperature for the first time. The protocol is applicable to a wide range of secondary amides including heterocycles, bio-active cinnamide derivatives and the diversification of therapeutic molecules. In-depth mechanistic investigations based on experimental outcomes and DFT calculations suggested an unconventional metal-ligand cooperation, where a ligand-centred radical plays a crucial role in initiating the reaction process., (© 2022 Wiley-VCH GmbH.)

Using a dicarboxylic acid, [1,1'-biphenyl]-4,4'-dicarboxylic acid (H 2 L1) and an exobidentate ligand, (1 E ,1' E )- N , N '-(1,4-phenylene)bis(1-(pyridin-4-yl)methanimine) (L2), two 3D interpenetrated networks, {[Zn 3 (L1) 3 (L2)]·9H 2 O} n (Zn-MOF) and {[Co 3 (L1) 3 (L2)(DMF)]·0.5DMF} n (Co-MOF), have been prepared in good yields. The crystal structure analysis of Zn-MOF and Co-MOF revealed that both have a 3D pillared-layer structure based on pinwheel trinuclear metal-carboxylate clusters as secondary building units (SBUs). Furthermore, the structures also exhibited three-fold interpenetration. Although the overall networks in Zn-MOF and Co-MOF showed significant resemblances, there are marked differences in their crystal structures, which are associated with the coordination environment of the metal centre and the binding modes of the carboxylates. Gas adsorption studies (N 2 at 77 K and 1 bar) indicated that Co-MOF is more porous than Zn-MOF. Magnetic measurements on Co-MOF indicate a significant antiferromagnetic interaction (45 K to 303 K) between trimeric Co(II) S = 3/2 spins through syn - syn carboxylato bridges. Both MOFs were studied for the Lewis acid catalyzed Knoevenagel condensation reactions between benzaldehydes and malononitrile with an active methylene group, where Zn-MOF was found to be a better catalyst than Co-MOF. This was supported by the Monte Carlo simulations indicating the better substrate binding ability of Zn-MOF than Co-MOF.

The α-aminonitriles are versatile building blocks in the synthesis of natural or artificial amino acids as well as important intermediates in organic synthesis. For their synthesis, the three-component Strecker reaction involving an aldehyde or a ketone together with amines and trimethylsilyl cyanide is used. In the literature, hydrothermally produced metal-based heterogeneous Lewis acid catalysts have been utilized in various solvents. In this work, we aimed at a greener approach toward such catalysis by (a) making two precatalysts with d 10 metal centers, {[Zn(hipamifba)(H 2 O)]·2H 2 O} n ( 1 ) and {[Cd(hipamifba)(H 2 O) 2 ]·2H 2 O} n ( 2 ) (where H 2 hipamifba = 4-(((4-((carboxymethyl) carbamoyl)phenyl)amino)methyl)benzoic acid), via an easy and scalable room-temperature method, and (b) showcasing the use of these coordination polymers (CPs) as very efficient, recyclable, and heterogeneous catalysts for the Strecker reaction to form α-aminonitriles in high yields under solvent-free reaction at ambient conditions. This has also allowed us to demonstrate the importance of open metal sites in such catalysis through an efficiency comparison between activated 1 and 2 . In addition, activated 2 exhibited a wide substrate scope including a natural product Girgensohnine , providing an example of a natural product synthesis by a CP catalyst via an organic transformation such as the Strecker reaction.

Background: There are very few prospective studies comparing simultaneous integrated boost versus sequential boost in the setting of definitive treatment modality of head and neck squamous cell cancer (HNSCC), especially in the Indian scenario., Materials and Methods: We prospectively randomized 50 patients with biopsy-proven squamous cell carcinoma of the oropharynx, hypopharynx, and larynx malignancies, stage T1-3, enlarged node measuring ≤3 cm that are planned for definitive radiotherapy with chemotherapy into either hypo-fractionated simultaneous integrated (Hypo-SIB VMAT) boost arm or conventional (Conv-VMAT) boost arm., Results: Most of the patients were men and aged less than 50 years. Patients with nodal involvement were 76% in Hypo-SIB VMAT and 80% in Conv-VMAT arm. The overall stage group distribution of II, III, and IVA were 16%, 44%, 40%, and 12%, 56%, and 32%, respectively, in both arms. All patients completed the intended treatment in both arms. Overall survival at the end of 2 years was 84% in Hypo-SIB VMAT arm and 80% in the Conv-VMAT arm (P = 0.25); disease-free survival (DFS) was 88% and 72%, respectively (P = 0.12); and locoregional recurrence-free survival (LRFS) was 92% and 84%, respectively (P = 0.38). All the acute and chronic toxicities in both the arms were comparable with no significant difference in any of the toxicities. The average overall treatment time (OTT) in Hypo-SIB VMAT arm is 39.4 days and in Conv-VMAT arm is 50.2 days (P = 0.00001) which is statistically significant., Conclusions: Accelerated Hypo-SIB VMAT has similar response and toxicities as compared to Conv-VMAT in the setting of definitive concurrent chemoradiation of HNSCC patients with the advantage of less OTT, faster treatment delivery, and patient compliance.

An extended class of stable mesoionic N-heterocyclic imines (mNHIs), containing a highly polarized exocyclic imine moiety, were synthesized. The calculated proton affinities (PA) and experimentally determined Tolman electronic parameters (TEPs) reveal that these synthesized mNHIs have the highest basicity and donor ability among NHIs reported so far. The superior nucleophilicity of newly designed mNHIs was utilized in devising a strategy to incorporate CO 2 as a bridging unit under reductive conditions to couple inert primary amides. This strategy was further extended to hetero-couplings between amide and amine using CO 2 . These hitherto unknown catalytic transformations were introduced in the diversification of various biologically active drug molecules under metal-free conditions. The underlying mechanism was explored by performing a series of control experiments, characterizing key intermediates using spectroscopic and crystallographic techniques., (© 2022 Wiley-VCH GmbH.)

We demonstrate that an in situ generated di-reduced phenalenyl (PLY) species accumulates sufficiently high energy and acts as a super electron donor to generate aryl radicals from aryl halides to accomplish Buchwald-Hartwig-type C-N cross-coupling reactions at room temperature. This catalytic protocol does not require any external stimuli such as heat, light, or cathodic current. This protocol shows a wide variety of substrate scope covering different genres of aryl and heteroaryl halides with various aromatic as well as aliphatic amines and late-stage functionalization of the well-known natural products. The control experiments, along with extensive density functional theory (DFT) calculations, unveil that the aryl radical is generated by a single electron transfer from the di-reduced PLY to the aryl halide substrate. The aryl radical acts as an electrophile and binds with amine, leading to the chemically driven radical-mediated C-N cross-coupling under transition-metal-free conditions.

Presence of Nepal in global clinical trials has been visibly negligible despite the history of conducting large scaled randomized controlled trial on Hepatitis E vaccine decades ago. Majority of the problem is attributed to the lack of collaborative work, financial and human resource constrains. COVID-19 pandemics seems to have triggered urgency among the authorities of Nepal leading to a substantial increase in the number of clinical trials in collaboration with national and international organizations/institutions. Immediately after detection of the first COVID-19 case on 13 January 2020, the Ethical Review Board (ERB) of NHRC received several research proposals, subsequently leading to the approval of the first clinical trial for COVID-19 on 01 July 2020 to investigate potential of traditional Ayurveda based medicine for COVID treatment. Soon, number of other clinical trial proposals received approval and implemented in the country, however budgetary allocation from the Government of Nepal (GON) was prioritized for COVID-19 outrage management and vaccination coverage only. Collaborations with various international institutions played a significant role in the successful implementation of large-scale clinical trials in the country and further laid the path for future. In this review paper we present the recent developments in clinical trials in Nepal, budgetary allocation from the government and the mechanisms in place for regulation of clinical research in the country along with challenges and way forward., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Utilizing the angular and rigid furan dicarboxylate (fdc 2- ) ion, a new series of four (1-4) metal-organic coordination networks (MOCNs) is synthesized in good yields through a one-pot self-assembly reaction in methanol under ambient conditions to demonstrate the effect of Cu 2 dimetal subunits, connected by flexible polypyridyl bis(tridentate) ancillary ligands, tpxn, where x refers to the number of methylene groups connecting the alkyl nitrogen atoms in the ancillary ligands and is equal to 2, 4, 6, and 7. The solid-state molecular structures of 1-4 are determined by single-crystal X-ray diffraction. A change in the dimensionality of the resultant MOCN is observed from a 1D coordination polymer (CP) for 1, 2, and 3 to a molecular rectangle for 4. Furthermore, each unit of 4 contains one NaClO 4 . Using electrospray ionization (ESI) mass spectrometry, their structural integrity in solution and their purity of existence as a single product are confirmed. Further characterization of 1-4 by FTIR and UV-vis (in solution and solid-state) spectroscopy, and FESEM and TEM is also reported. The presence of unsaturated metal centers in 1-4 provided an opportunity to compare their Lewis acid catalytic activities for the Knoevenagel condensation reaction of malononitrile with various aldehydes.

Like the world over, Nepal was also hard hit by the second wave of COVID-19. We audited the clinical care provided to COVID-19 patients admitted from April to June 2021 in a tertiary care hospital of Nepal. This was a cohort study using routinely collected hospital data. There were 620 patients, and most (458, 74%) had severe illness. The majority (600, 97%) of the patients were eligible for admission as per national guidelines. Laboratory tests helping to predict the outcome of COVID-19, such as D-dimer and C-reactive protein, were missing in about 25% of patients. Nearly all (>95%) patients with severe disease received corticosteroids, anticoagulants and oxygen. The use of remdesivir was low (22%). About 70% of the patients received antibiotics. Hospital exit outcomes of most (>95%) patients with mild and moderate illness were favorable (alive and discharged). Among patients with severe illness, about 25% died and 4% were critically ill, needing further referral. This is the first study from Nepal to audit and document COVID-19 clinical care provision in a tertiary care hospital, thus filling the evidence gap in this area from resource-limited settings. Adherence to admission guidelines was excellent. Laboratory testing, access to essential drugs and data management needs to be improved.

In this report, the effect of rare-earth (RE 3+ ) ion substitution on structural, microstructural, and electrical properties in barium bismuth titanate (BaBi 4 Ti 4 O 15 ) (BBTO) Aurivillius ceramics has been investigated. The Rietveld refinements on X-ray diffraction (XRD) patterns confirm that all the samples have an orthorhombic crystal system with A2 1 am space group. Meanwhile, temperature dependent synchrotron XRD patterns reveal that the existence of dual phase in higher temperature region. The randomly oriented plate-like grains are experimentally strived to confirm the distinctive feature of bismuth layered Aurivillius ceramics. The broad band dielectric spectroscopic investigation signifies a shifting of ferroelectric phase transition (T m ) towards low temperature region with a decrease of the RE 3+ -ionic radii in BBTO ceramics. The origin of diffuse ferroelectric phase transitions followed by stabilization of the relaxor ferroelectric nature at high frequency region is explained using suitable standard models. The temperature dependent ac and dc conductivity results indicate the presence of double ionized oxygen vacancies in BBTO ceramics, whereas the dominance of single ionized oxygen vacancies is observed in RE-substituted BBTO ceramics. The room temperature polarization vs. electric field (P-E) hysteresis loops are shown to be well-shaped symmetric for BBTO ceramics, whereas slim asymmetric ferroelectric characteristics developed at RE-substituted BBTO ceramics., (© 2022. The Author(s).)

Herein, we report the synthesis of a benzimidazolylidene-stabilized borane adduct and its borenium ion. This borenium ion was used as a metal-free catalyst for hydrogenating various substituted quinoline N-heterocycles under ambient conditions. Furthermore, this method was utilized to synthesize two drug molecules: galipinine and angustureine. A detailed DFT study was performed to understand this metal-free catalytic hydrogenation .

Industrialization and urbanization are mainly responsible for environmental pollution generating enormous amount of wastewater which needs to be treated. Wastewaters from various sources are toxic to humans and livestock, as well as posing environmental risks. Various treatment approaches have been used for the elimination of contaminants from water and wastewater. Coagulation/flocculation processes are the most commonly used techniques in water treatment for improving the condition of turbid water and removing suspended particles by destabilization and the creation of larger, heavier flocs that aid in sedimentation. Flocculants, both organic and inorganic, have long been used in wastewater treatment. The use of natural coagulants/flocculants for water and wastewater treatment has become essential due to the health risks associated with chemical flocculants. Tannin, a natural coagulant, has been suggested as substitute of chemical coagulants. Tannins are present in the leaves, fruits, barks, roots, and wood of trees as a secondary metabolite. Tannin-based coagulants derived from a variety of plant sources have been successfully used in the treatment of water and wastewater. This review summarises the current status and strategies on applications of tannin-based coagulants exploiting the eco-friendly green materials in water and wastewater remediation for the sake of pollution free environment., (© 2022. Akadémiai Kiadó Zrt.)

Herein we report the first metal-free regioselective Markovnikov ring-opening of epoxides (selectivity up to 99%) using an abnormal N-heterocyclic carbene (aNHC) to yield secondary alcohols. DFT calculations and X-ray crystallography suggest that the Markovnikov selectivity originates from the high nucleophilicity and steric factors associated with the aNHC.

Objective: The world continues to face the COVID-19 crisis, and efforts are underway to integrate traditional medicine interventions for its effective management. The study aimed to determine the efficacy of the "AYURAKSHA" kit in terms of post-interventional percentage of COVID-19 IgG positivity, immunity levels, and quality of life (QoL) against COVID-19., Method: This was a non-randomized controlled, prospective intervention trial, done after the distribution of 80,000 AYURAKSHA kits (constituent of Sanshamani Vati, AYUSH Kadha, and Anu Taila) among Delhi police participants in India. Among 47,827 participants, the trial group ( n = 101) was evaluated with the positivity percentage of IgG COVID-19 and Immune Status Questionnaire (ISQ) scores as a primary outcome and the WHO Quality of Life Brief Version (QOL BREF) scores along with hematological parameters as a secondary outcome in comparison to the control group ( n = 71)., Results: The data showed that the percentage of COVID-19 IgG positivity was significantly lower in the trial group (17.5 %) as compared to the control group (39.4 %, p = 0.003), indicating the lower risk (55.6%) of COVID-19 infection in the trial group. The decreased incidence (5.05%) and reduced mortality percentage (0.44%) of COVID-19 among Delhi police officers during peak times of the pandemic also corroborate our findings. The ISQ score and WHO-QOL BREF tool analysis showed the improved scores in the trial group when compared with the controls. Furthermore, no dysregulated blood profile and no increase in inflammation markers like C-reactive protein, erythrocyte sedimentation rate, Interleukin-6 (IL-6) were observed in the trial group. However, significantly enhanced ( p = 0.027) IL-6 levels and random blood sugar levels were found in the control group ( p = 0.032), compared to a trial group ( p = 0.165) post-intervention. Importantly, the control group showed more significant ( p = 0.0001) decline in lymphocyte subsets CD3 + (% change = 21.04), CD4 + (% change = 20.34) and CD8 + (% change = 21.54) levels than in trial group, confirming more severity of COVID-19 infection in the control group., Conclusion: The AYURAKSHA kit is associated with reduced COVID-19 positivity and with a better quality of life among the trial group. Hence, the study encourages in-depth research and future integration of traditional medicines for the prevention of the COVID-19 pandemic., Clinical Trial Registration: http://ctri.nic.in/, identifier: CTRI/2020/05/025171., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nesari, Kadam, Vyas, Huddar, Prajapati, Rajagopala, More, Rajagopala, Bhatted, Yadav, Mahanta, Mandal, Mahto, Kajaria, Sherkhane, Bavalatti, Kundal, Dharmarajan, Bhojani, Bhide, Harti, Mahapatra, Tagade, Ruknuddin, Venkatramana Sharma, Rai, Ghildiyal, Yadav, Sandrepogu, Deogade, Pathak, Kapoor, Kumar, Saini and Tripathi.)

Obesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (-10.96 kcal/mol against PPARα and -10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (-14.88 kcal/mol against PPARα and -13.64 kcal/mol against PPARγ), and its aglycone, quercetin (-10.08 kcal/mol in PPARα and -9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment., (Copyright © 2022. Published by Elsevier Ltd.)

Phenalenyl, a zigzag-edged odd alternant hydrocarbon unit can be found in the graphene nanosheet. Hückel molecular orbital calculations indicate the presence of a nonbonding molecular orbital (NBMO), which originates from the linear combination of atomic orbitals (LCAO) arising from 13 carbon atoms of the phenalenyl molecule. Three redox states (cationic, neutral radical, and anionic) of the phenalenyl-based molecules were attributed to the presence of this NBMO. The cationic state can undergo two consecutive reductions to result in neutral radical and anionic states, stepwise, respectively. The phenalenyl-based radicals were found as crucial building blocks and attracted the attention of various research fields such as organic synthesis, material science, computation, and device physics. From 2012 onward, a strategy was devised using the cationic state of phenalenyl-based molecules and in situ generated phenalenyl radicals, which created a new domain of catalysis. The in situ generated phenalenyl radicals were utilized for the single electron transfer (SET) process resulting in redox catalysis. This emerging range of applications rejuvenates the more than six decades-old phenalenyl chemistry. This review captures such developments ranging from fundamental understanding to multidirectional applications of phenalenyl-based radicals.