Copper-mediated cyclization of thiosemicarbazones leading to 1,3,4-thiadiazoles: Structural elucidation, DFT calculations, in vitro biological evaluation and in silico evaluation studies.

Cancer's global impact necessitates innovative and less toxic treatments. Thiosemicarbazones (TSCs), adaptable metal chelators, offer such potential. In this study, we have synthesized N (4)-substituted heterocyclic TSCs from syringaldehyde (TSL1, TSL2), and also report the unexpected copper-mediated cyclization of the TSCs to form thiadiazoles (TSL3, TSL4), expanding research avenues. This work includes extensive characterization and studies such as DNA/protein binding, molecular docking, and theoretical analyses to demonstrate the potential of the as-prepared TSCs and thiadiazoles against different cancer cells. The DFT results depict that the thiadiazoles exhibit greater structural stability and reduced reactivity compared to the corresponding TSCs. The docking results suggest superior EGFR inhibition for TSL3 with a binding constant value of - 6.99 Kcal/mol. According to molecular dynamics studies, the TSL3-EGFR complex exhibits a lower average RMSD (1.39 nm) as compared to the TSL1-EGFR complex (3.29 nm) suggesting that both the thiadiazole and thiosemicarbazone examined here can be good inhibitors of EGFR protein, also that TSL3 can inhibit EGFR better than TSL1. ADME analysis indicates drug-likeness and oral availability of the thiadiazole-based drugs. The DNA binding experiment through absorption and emission spectroscopy discovered that TSL3 is more active towards DNA which is quantitatively calculated with a Kb value of 4.74 × 106 M-1, Kq value of 4.04 × 104 M-1and Kapp value of 5 × 106 M-1. Furthermore, the BSA binding studies carried out with fluorescence spectroscopy showed that TSL3 shows better binding capacity (1.64 × 105 M-1) with BSA protein. All the compounds show significant cytotoxicity against A459-lung, MCF-7-breast, and HepG2-liver cancer cell lines; TSL3 exhibits the best cytotoxicity, albeit less effective than cisplatin. Thiadiazoles demonstrate greater cytotoxicity than the TSCs. Overall, the promise of TSCs and thiadiazoles in cancer research is highlighted by this study. Furthermore, it unveils unexpected copper-mediated cyclization of the TSCs to thiadiazoles.

In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation - Targeting Mpro and pan-coronavirus post-fusion Spike protein.

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.

Pseudoexfoliative Deposits on an Intraocular Lens.

This case report discusses the finding of pseudoexfoliative material on the intraocular lens implant of a patient with a history of pseudoexfoliation syndrome and secondary glaucoma.

Bibliometric Analysis and Visualization of the Extrahepatic Portal Venous Obstruction Publication Landscape.

Introduction: A scientometric analysis was conducted to characterize the global research publications in extrahepatic portal venous obstruction (EHPVO), and state-of-the-art visualization graphics were generated to provide insight into specific bibliometric variables. Materials and Methods: The Web of Science database was accessed for research productivity and bibliometric variables of countries, institutions, authors, journals, and content analysis of top-20 cited documents were performed. Collaborative networks and co-occurrence of keywords map were generated using VOSviewer software. Results: Two hundred and sixteen records were retrieved with an annual growth rate of 2.53%. India is the leading country in productivity (n = 4339), followed by the USA and China. Post Graduate Institute of Medical Education and Research, Chandigarh, was the top productive institute. Sarin SK was the most prolific author, having the highest citations received and h-index. The hotspot topics were "portal hypertension," "cirrhosis," "children," "biliopathy/cholangiopathy," "liver fibrosis," and "liver transplantation" as per keyword co-occurrence networking. J Gastroenterol Hepatol had the most publications of EHPVO research as well the h-index. Regarding collaborative network mapping, the USA and Primignani M were the significant nodes among country and author, respectively. Conclusion: EHPVO research publication volume is low but is gradually progressing with dominant contributions from Indian institutes and authors. Most highly cited articles are of low level of evidence, and multi-institutional collaborative research can be the way forward.

Changing pattern of childhood blindness in eight North-Eastern states and review of the epidemiological data of childhood blindness of India.

PURPOSE: To assess the causes of visual impairment and blindness in children in all the schools for the blind in eight northeastern states and to determine its temporal trend, and to analyze the result with reference to various regional epidemiological data on childhood blindness in India. METHODS: Children aged ≤16 years, with a visual acuity of ≤6/18 in the better eye, attending 17 schools for the blind were examined between November 2018 and March 2020. WHO protocol and reporting format was used for the evaluation, diagnosis, and classification of the causes. RESULTS: Out of 465 eligible study participants, 93.76% were blind and only 12.26% of causes were avoidable. Anatomical causes of childhood blindness were whole globe (43.2%), cornea (17.20%), optic nerve (12.04%), retina (9.68%), and lens (9.46%). Etiological causes were unknown (52.69%), hereditary (26.02%), intrauterine (15.05%), and 26.08% had blinding congenital ocular abnormality (s). Regional temporal trend revealed a decrease in corneal and childhood causes and an increase in retina, optic nerve, hereditary, and intrauterine causes. CONCLUSION: A constellation of causes were differentiable but matched with the overall emerging trend of childhood blindness in India. Higher corneal, unavoidable, and unknown causes suggest a region-specific action plan for controlling childhood blindness as well as rehabilitation.

Transient myopia due to choroidal effusion: A novel ocular complication of COVID-19 infection.

COVID-19 was declared as a global pandemic by the WHO in 2020. Although it is a respiratory virus, ocular complications and manifestations of the infection have been reported in different forms. We report a case of transient myopia and narrow angles due to choroidal effusion following infection by the SARS-COV-2 virus. We propose that the ability of the virus to incite an inflammatory response in the host body may be the mechanism behind the disease entity. This is a novel, previously undocumented ocular complication in case of a COVID-19 infection.

A Bibliometric Study of the Pediatric Inguinal Hernia Publication Landscape from the Web of Science Database.

Background: The number of times a research work gets cited by another article is one of the article-level metrics for assessing the quality of a research publication. Citation analysis by bibliometric review has been performed in several disciplines. The current study was aimed to systematically review the literature available on pediatric inguinal hernia since 1960 in terms of the 25 most cited articles in this field and analyze the bibliometric variables author and organizational collaborative patterns. Methods: Thomson Reuters Web of Science citation indexing database and research platform were used to retrieve the most cited articles in pediatric inguinal hernia (PIH) using appropriate search strings. The characteristics (name of authors, the total number of authors, the title of publication, journal of publication, year of publication, etc.) of the 25 top-cited articles were recorded. Specific bibliographical parameters were derived and analyzed. Visualization maps were generated using VOSviewer software. Results: The analysis revealed that the Journal of Pediatric Surgery was leading the choice of journal for publication. While most of the publications originated from the United States of America, Schier was the most influential author. Five of the eight top-productive authors are also the most connected. Conclusion: Articles on laparoscopic repair in PIH have been heavily cited. Following the United States of America, Turkey stands out as the topmost productive country in PIH. The publications on PIH show that "collaboration" is the bridging force between productivity and influence on the academic community.

Pathologic evidence of retinoblastoma seeds supported by field emission scanning electron microscopy and Raman spectroscopy.

PURPOSE: The aim of this study was to examine the pathology of retinoblastoma (RB) seeds with supportive evidence by field emission scanning electron microscopy and Raman spectroscopy. METHODS: This study was a laboratory-based observational study. Enucleated eyeballs received in the ocular pathology department of a tertiary eye care center in northeast India were included in the cohort after obtaining written informed consent during the surgery. The study was carried out for 6 years (2015-2020). Most of the eyeballs were Group-E RBs. Standard eyeballs sectioning were done by bread loaf techniques. Gross documentations included RB seeds seen in the smallest calotte done with utmost care. Seeds were documented also in permanent sections. Scanning electron microscopy and Raman spectroscopy were carried out in an index case. RESULTS: Out of the total 59 cases, 35 RB cases had different seedings. The mean age at enucleation was 2.9 years. RB seeds were seen in vitreous (n = 19), subretinal plus vitreous (n = 7), anterior chamber (n = 1), over crystalline lens (n = 3), retinal surface (n = 1), retinal pigment epithelium (RPE; n = 2), subretinal (n = 1), calcified seeds (n = 2). Other characteristics were dusts (n = 7), clouds (n = 11), spheres (n = 4), and unspecified type (n = 13). Histopathological high-risk factors showed significant choroidal (n = 22) and optic nerve (n = 15) involvement. Few cases had extraocular spread. Undifferentiated tumor (n = 24) was seen with higher evidence of necrosis (n = 23). Raman spectra differentiated the seeds from the normal tissue on the basis of lipid and protein content. CONCLUSION: This study highlights the different types of RB seeds with high-risk factors. The morphology of those seeds showed the difference between vitreous and subretinal seeds under advanced microscopic observations.

Safety and Efficacy of Long-Acting Insulins Degludec and Glargine Among Asian Patients With Type 2 Diabetes Mellitus: A Meta-Analysis.

Background Global variation in susceptibility to diabetes, insulin sensitivity, and regimen intensity poses a challenge for clinicians regarding the optimal choice of insulin therapy. The current study was carried out to see the relative safety and efficacy of currently available long-acting insulins among the type 2 diabetic Asian population. Methods A systematic literature search was done using various search engines (PubMed, Cochrane, Google Scholar, Scopus, and Embase) and included published randomized controlled trials (RCTs) in English before December 2019. Further, a manual search was performed by screening the reference list of the identified articles. Results We included four RCTs with 534 participants (349 in the insulin degludec group and 185 in the insulin glargine group) with type 2 diabetes mellitus (T2DM). Results show that both insulin glargine and degludec are equally efficacious in reducing fasting blood glucose (mean difference is -4.45, confidence interval -13.32- 4.43, I2=67%) and HbA1c (glycosylated hemoglobin) (mean difference is 0.12, confidence interval -0.12-0.35, I2=0%). However, insulin glargine was associated with lower risks of hypoglycemia (risk ratio = 0.9684, confidence interval- 0.8003- 1.1717, I2=30%). Conclusion Insulin glargine and degludec are comparable in achieving glycemic control with fewer hypoglycemic episodes in the insulin glargine-treated group.

Correction: Bueckert et al. Infectivity of SARS-CoV-2 and Other Coronaviruses on Dry Surfaces: Potential for Indirect Transmission. Materials 2020, 13, 5211.

The authors wish to make the following corrections to this paper [1]:Throughout the paper's text and in the table, "HCoV-299E" is referred to a few times [...].

Ion Diffusion through Nanocellulose Membranes: Molecular Dynamics Study.

One of the most promising applications of nanocellulose is for membranes for energy storage devices including supercapacitors, batteries, and fuel cells. Several recent studies reported the fabrication of cellulose-based membranes where ionic conductivity was confined to channels. So far, theoretical understanding of the effect of the nanoconfinement and surface charged groups on the diffusion coefficient of ions in cellulose nanochannels is missing. In the present study, we perform atomistic molecular dynamics simulations to provide this theoretical understanding and unravel mechanisms affecting the ionic diffusion in nanochannels. We demonstrate that the diffusion coefficient of ions in cellulose nanochannels is reduced in comparison to its bulk value. The change of the diffusion coefficient depends on the density of charged surface groups in nanochannels and the channel height, and it is primarily caused by the Coulomb interaction between the ions and the surface. We believe that our results reveal an important structure/property relationship in cellulose nanochannels, and they show that accounting for the dependence of the diffusion coefficient on the charge of the surface groups and channel height can be important for the Nernst-Plank-Poisson modeling of the ion conductivity in nanomembranes as well as for accurate fitting the experimental data to extract the material parameters.

Infectivity of SARS-CoV-2 and Other Coronaviruses on Dry Surfaces: Potential for Indirect Transmission.

The unwavering spread of COVID-19 has taken the world by storm. Preventive measures like social distancing and mask usage have been taken all around the globe but still, as of September 2020, the number of cases continues to rise in many countries. Evidently, these measures are insufficient. Although decreases in population density and surges in the public's usage of personal protective equipment can mitigate direct transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), indirect transmission of the virus is still probable. By summarizing the current state of knowledge on the stability of coronaviruses on dry materials, this review uncovers the high potential for SARS-CoV-2 transmission through contaminated surfaces (i.e., fomites) and prompts future research. Fully contextualized data on coronavirus persistence are presented. The methods and limitations to testing the stability of coronaviruses are explored, and the SARS-CoV-2 representativeness of different coronaviruses is analyzed. The factors which dictate the persistence of coronaviruses on surfaces (media, environmental conditions, and material-type) are investigated, and the review is concluded by encouraging material innovation to combat the current pandemic. To summarize, SARS-CoV-2 remains viable on the timescale of days on hard surfaces under ambient indoor conditions. Similarly, the virus is stable on human skin, signifying the necessity of hand hygiene amidst the current pandemic. There is an inverse relationship between SARS-CoV-2 surface persistence and temperature/humidity, and the virus is well suited to air-conditioned environments (room temperature, ~ 40% relative humidity). Sunlight may rapidly inactivate the virus, suggesting that indirect transmission predominantly occurs indoors. The development of antiviral materials and surface coatings would be an extremely effective method to mitigate the spread of COVID-19. To obtain applicable data on the persistence of coronaviruses and the efficiency of virucidal materials, future researchers should understand the common experimental limitations outlined in this review and plan their studies accordingly.

Theoretical Rationalization of Self-Assembly of Cellulose Nanocrystals: Effect of Surface Modifications and Counterions.

The hierarchical self-assembly of cellulose nanocrystals (CNCs) is an important phenomenon occurring naturally in plant cell walls. Utilization of this assembly for advanced applications requires a fundamental theoretical understanding of interactions between the CNCs, which is still incomplete. Hence, in this work, we used molecular dynamics simulations to study the effect of surface modification on the interactions between the CNCs and the resulting bundling process. We consider two types of common surface modifications of native CNCs, sulfated CNCs (SCNCs) and TEMPO-oxidized CNCs (TCNCs), in the presence of two types of counterions, Na+ and Ca2+, in solution. We used the umbrella sampling method to calculate the potential of the mean force (PMF), and we found that the strength of interaction between the modified CNCs decreases, compared with the native CNCs. The strength of interaction for TCNCs is almost similar to that for SCNCs at the same level of surface substitution, whereas the type of counterion has a strong effect on the PMF with a higher interaction energy between the CNCs in the presence of a divalent counterion as compared to a monovalent counterion. Finally, we studied the self-assembly of CNCs into a hexagonal bundle for the native CNCs and sulfated CNCs focusing on the twist of the bundle, bound water inside the bundle, inter-CNC gap, and interaction energy between the CNCs in the bundle, and the effect of the counterions on the morphology of the bundle. The equilibrium spacing of the CNCs within the bundle is found to be consistent with the results of PMF calculations for the minimum separation distance between the respective crystal surfaces.

New Patchy Particle Model with Anisotropic Patches for Molecular Dynamics Simulations: Application to a Coarse-Grained Model of Cellulose Nanocrystal.

Self-assembly is ubiquitous in nature and underlies the formation of many complex systems from the molecular to the macroscopic scale. Kern-Frenkel-like patchy particles are powerful models to investigate this phenomenon by computational methods such as Monte Carlo or molecular dynamics simulations. However, in these models the interactions are mediated by circular patches at the particle surface, which can be hardly mapped to realistic systems, containing for instance faceted particles with rectangular surfaces. In this paper we extend the model to take into account such geometries, and we use it to build a supra coarse-grained model of the cellulose nanocrystal where the interactions are parametrized against all-atomistic molecular dynamics simulations. The formation of cholesteric ribbons and defects in cholesteric droplets of the cellulose nanocrystal are investigated and confirm experimental behavior reported in the literature. The flexibility of this new patchy particle model makes it a powerful tool to develop supra coarse-grained models of self-assembly for large space and time scales and should find a broad range of applications for self-assembly in chemical and biological systems.

Tubercular granuloma mimicking pyogenic liver abscess.

Hepatic Tuberculosis (TB) is extremely rare without miliary involvement in immunocompetent patients. Even in countries like India where TB is a major public health problem only few cases have been diagnosed and treated. We report a case of an immunocompetent patient who presented with undiagnosed pyrexia of 11 days, was initially diagnosed as pyogenic liver abscess, he did not responded to treatment and on liver biopsy was diagnosed as hepatic tuberculoma. Antitubercular treatment (ATT) was started and the patient responded well. We concluded that though hepatic TB is rare in immunocompetent patient, it is important to keep it as a differential diagnosis in patients of liver abscesses who are not responding to treatment in order to avoid needless investigations.

Poly(3-hexylthiophene) (P3HT) and Phenyl-C61-Butyric Acid Methyl Ester (PC61BM) Based Bulk Heterojunction Solar Cells Containing Silica and Titanium Dioxide Nanorods: Molecular Dynamics Simulations.

Molecular dynamics simulations are used to demonstrate the effects of introducing anisotropicallyshaped silica (SiO2) and titanium dioxide (TiO2) nanoparticles on the morphology of poly(3-hexylthiophene) (P3HT)-phenyl-C61-butyric acid methyl ester (PC61BM) bulk heterojunction (BHJ) solar cells. The morphological compatibility and structure formation upon introduction of nanorods to the mixture of P3HT and PCBM are systematically studied by calculating several parameters that are known to influence the performance of BHJ. The anisotropically-shaped nanorods self-assemble into a variety of macroscopic structures, depending on the aspect ratio, and alter the phase morphology of PCBM. Several morphological properties such as domain size, crystallinity of the polymer phase and surface area of contact between P3HT and PCBM are found to be influenced by the presence of these nanorods. At low aspect ratios of the nanorods, the nanorod-PCBM clusters formed are kinetically-trapped and heavily branched, resulting in lower P3HT domain size and crystallinity. As the aspect ratio increases, the nanorods align parallel to each other and form two-dimensional sheet-like structures with PCBM. The P3HT crystallinity near the surface of longer nanorods were found to be higher. These changes in the morphological properties of the bulk heterojunction can be used as a benchmark to study the ternary blend solar cells with enhanced power conversion efficiency.