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Several studies have amply proved that air pollution negatively impacts human health. The nature of its effects on COVID-19 has, of late, become an area for investigation across the world. The present study reviews reports in the literature that centred on whether the presence and impact of air pollutants magnified the symptoms and actions of COVID-19 and whether preventive measures taken, starting with lockdown, affected air pollution levels. This may help to establish causality, if any, between pollution and COVID-19. Studies were chosen to ensure representation of all continents with diverse climatic conditions with the exception of Australia. Most of the studies concluded that air pollutants declined as a result of the lockdowns imposed to constrain the spread of COVID-19. A significant reduction in NO2 is observed along with the resultant increase in tropospheric ozone in the atmosphere. The inference is untrue in hostile meteorological conditions. According to some studies, reduction in pollutants aided in contracting the spread and severity of COVID-19. On the other hand, hostile weather conditions incited the spread and magnitude of COVID-19. A governmental policy inference could be that government intervention through imposing a lockdown would reduce air pollution and ensure the health safety of the people, but economic growth considerations need to be balanced against the benefit for public health.

The theory of Neutrosophy fuzzy set is the extension of the fuzzy set that deals with imprecise and indeterminate data Neutrosophy is a new branch of Philosophy. We already conceptualized the Neutrosophic fuzzy bi-ideals of Near –subtraction Semigroups (NFBI).In this article, We extend our study to strong bi-ideals. We examine some of its fundamentals and algebraic structures. Our aim of this manuscript are given as follows: (i)To explore the new ideas in Neutrosophic fuzzy Near-subtraction semigroups of said bi-ideals and strong bi-ideals. (ii)To examine the some basic properties and fundamentals. (iii)Also expand the direct product and regularity of Neutrosophic fuzzy strong bi-ideals (NFSBI) of a Near- Subtraction Semigroups.

Abstract Groundwater chemistry is mainly governed by lithological variations, space and resident time. In addition, hydrogeochemical characteristics of groundwater in the lithological contact zones are too complex. Hence, Cretaceous–Tertiary (KT) boundary from Ariyalur district, Tamilnadu, India, was selected for this study to identify the hydrogeochemistry of groundwater. This study includes 284 groundwater samples from four different seasons (pre-monsoon, post-monsoon, southwest monsoon and northeast monsoon). Groundwater samples were collected and analysed for major cations and anions, including physical parameters using standard procedures. High electrical conductivity (EC) showed the longer residence time of groundwater in hard rock region at the central and southern part of the study area. Ca2+, Na+, Cl− and HCO3 − are the dominant ions in all the four seasons. The seasonal composition migration was observed from Na–Ca–Cl–HCO3 type to Na–Mg–Cl–HCO3 type, and Ca-HCO3 is the predominant water type in piper plot. Interpretation of data reveals that the groundwater quality was unsuitable for domestic and irrigation purposes during pre- and southwest monsoon seasons. Rock–water interaction and dissolution of minerals are the main sources of groundwater chemistry. Agriculture activities during monsoonal seasons also play a role in controlling the hydrogeochemistry of groundwater in this region.

There has been a dramatic increase in the frequency of arboviral disease epidemics among humans and domestic animals worldwide in recent decades. Some of these infections have also undergone significant geographical expansion owing to uncontrolled urbanization leading to changes in vector distribution and/or adaptation of the etiologic agent to more anthropophilic vectors. Arboviral infections such as chikungunya have re-emerged in certain parts of the world, such as India (where chikungunya re-emerged in 2006 after 32 years of quiescence). Existing surveillance systems for arboviral infections in developing countries face several issues, such as being dependent on reporting of loosely defined clinical syndromes and infrequent laboratory confirmation. The recent re-emergence of Zika virus infections and its complications in South America underscore the urgent need for advancements in scientific knowledge on the biology of the arboviral agents and their vectors, innovations concerning diagnostic technologies, vector control measures, and therapeutic approaches. India, a tropical country, harbors an abundance of arthropod vectors capable of hosting and propagating viral infections. These vectors can transmit infections within humans, animals and also across species. This review focuses on viral infections in humans transmitted by arthropod vectors.

Background: Arginase deficiency is considered a masquerader of diplegic cerebral palsy. The rarity of hyperammonemic crisis and the slowly progressive course has made it a unique entity among the urea cycle defects. Objectives: The aim of our study is to describe the varied phenotypic spectrum of children with arginase deficiency. Methodology: This retrospective study included children and adolescents aged

Biomedical waste (BMW) is any sort of litter generated in the course of human or animal research operations, such as diagnosis, treatment, or immunization, or during the development or trial of pharmaceutical products or in health camps. In dental sectors, BMW, if not adequately handled, can provide a number of health risks to dental practitioners, patients, and other dental healthcare service providers who operate in dental offices. The aim of the study is to examine the knowledge, awareness, and practice of BMW segregation among dental offices. A well-framed questionnaire containing 10 self-structured questions was formed and distributed among 100 students of dentistry through an online Google Forms link. The results were collected, tabulated, and statistically analyzed using the Software SPSS. Chi-square test was performed to assess the P value. Biological waste segregation was known to 98% of the participants, in which most of them had more than 10 years of expertise in dentistry. It is evident that dentists with a lot of experience over the years in the field of dentistry possess considerably increased awareness regarding the segregation of BMWs in their dental offices. Chi-square test done between the years of experience in dentistry and the knowledge on BMW segregation reveals that 0.031 < 0.05 is the P value, which is statistically significant. Most dentists having experience of above 10 years in the field of dentistry have excellent knowledge and practice of segregating BMWs in their dental offices.

Taking an online course requires more motivation and self-discipline than taking a classroom-based course. One or more teachers and peers may keep a student responsible for their course work in a classroom. Online classes, on the other hand, enable us to set our own targets, chart our success, and follow deadlines. An awareness-based, self-administered questionnaire was created. The target audience for the study received a link to the questionnaire through Google Docs. The participants were given a thorough explanation of the survey's objectives. Pie charts with a frequency table were created after the survey findings were known. A Chi-square test was used to examine for associations in the statistics, and a P = 0.05 was considered statistically significant. The overall satisfaction level with online classes among students was, 57% were not satisfied with online classes, 31% were satisfied, and 12% were extremely satisfied. Most commonly students were not satisfied with both genders. However, majority of the females were not satisfied. This difference was statistically significant (Pearson's Chi-square value: 1.999, df = 2, P = 0.368 (>0.05) – significant). Eighty percent of the students have faced difficulties while attending online classes. However, 92% of the students have agreed that the technology helped them to attend their online classes.

X-rays are electromagnetic waves produced by an X-ray machine and are used to observe the internal structures of patients. The X-rays pass through the body before being detected by the detector file or a digital detector behind the patient. To analyze the knowledge, awareness, and practice on conventional radiographic method and processing among the dental students. A well-framed questionnaire consisting of 10 questions were prepared and distributed among 100 dental professionals and students through the online Google forms link. The data were collected, tabulated in Excel sheets, and analyzed using the SPSS software. The Chi-square test was used to assess the P value. Sixty-five percentage of the participants are aware of conventional radiographic methods and 35% are not aware. The Chi-square test was done giving a P = 0.001 (

Abstract Background Aspergillus flavus, one of the causative agents of human fungal keratitis, can be phagocytosed by human corneal epithelial (HCE) cells and the conidia containing phagosomes mature into phagolysosomes. But the immunological responses of human corneal epithelial cells interacting with A. flavus are not clear. In this study, we report the expression of immune response related genes of HCE cells exposed to A. flavus spores using targeted transcriptomics. Methods Human corneal epithelial cell line and primary cultures were grown in a six-well plate and used for coculture experiments. Internalization of the conidia was confirmed by immunofluorescence microscopy of the colocalized endosomal markers CD71 and LAMP1. Total RNA was isolated, and the quantity and quality of the isolated RNA were assessed using Qubit and Bioanalyzer. NanoString nCounter platform was used for the analysis of mRNA abundance using the Human Immunology panel. R-package and nSolver software were used for data analysis. KEGG and FunRich 3.1.3 tools were used to analyze the differentially expressed genes. Results Different morphotypes of conidia were observed after 6 h of coculture with human corneal epithelial cells and found to be internalized by epithelial cells. NanoString profiling showed more than 20 differentially expressed genes in immortalized human corneal epithelial cell line and more than ten differentially expressed genes in primary corneal epithelial cells. Distinct set of genes were altered in their expression in cell line and primary corneal epithelial cells. KEGG pathway analysis revealed that genes associated with TNF signaling, NF-KB signaling, and Th17 signaling were up-regulated, and genes associated with chemokine signaling and B cell receptor signaling were down regulated. FunRich pathway analysis showed that pathways such as CDC42 signaling, PI3K signaling, and Arf6 trafficking events were activated by the clinical isolates CI1123 and CI1698 in both type of cells. Conclusions Combining the transcript analysis data from cell lines and primary cultures, we showed the up regulation of immune defense genes in A. flavus infected cells. At the same time, chemokine signaling and B cell signaling pathways are downregulated. The variability in the expression levels in the immortalized cell line and the primary cultures is likely due to the variable epigenetic reprogramming in the immortalized cells and primary cultures in the absence of any changes in the genome. It highlights the importance of using both cell types in host-pathogen interaction studies.

Abstract Background miRNAs are regulatory transcripts established as repressors of mRNA stability and translation that have been functionally implicated in carcinogenesis. miR-10b is one of the key onco-miRs associated with multiple forms of cancer. Malignant gliomas exhibit particularly striking dependence on miR-10b. However, despite the therapeutic potential of miR-10b targeting, this miRNA’s poorly investigated and largely unconventional properties hamper the clinical translation. Methods We utilized Covalent Ligation of Endogenous Argonaute-bound RNAs and their high-throughput RNA sequencing to identify miR-10b interactome and a combination of biochemical and imaging approaches for target validation. They included Crosslinking and RNA immunoprecipitation with spliceosomal proteins, a combination of miRNA FISH with protein immunofluorescence in glioma cells and patient-derived tumors, native Northern blotting, and the transcriptome-wide analysis of alternative splicing. Results We demonstrate that miR-10b binds to U6 snRNA, a core component of the spliceosomal machinery. We provide evidence of the direct binding between miR-10b and U6, in situ imaging of miR-10b and U6 co-localization in glioma cells and tumors, and biochemical co-isolation of miR-10b with the components of the spliceosome. We further demonstrate that miR-10b modulates U6 N-6-adenosine methylation and pseudouridylation, U6 binding to splicing factors SART3 and PRPF8, and regulates U6 stability, conformation, and levels. These effects on U6 result in global splicing alterations, exemplified by the altered ratio of the isoforms of a small GTPase CDC42, reduced overall CDC42 levels, and downstream CDC42 -mediated effects on cell viability. Conclusions We identified U6 snRNA, the key RNA component of the spliceosome, as the top miR-10b target in glioblastoma. We, therefore, present an unexpected intersection of the miRNA and splicing machineries and a new nuclear function for a major cancer-associated miRNA.

Abstract Background Salmonella belongs to the Enterobacteriaceae family, a gram-negative, non-spore-forming, rod-shaped, motile, and pathogenic bacteria that transmit through unhygienic conditions. It is estimated that 21 million new infections arise every year, resulting in approximately 200,000 deaths. It is more prevalent among children, the old aged, and immunocompromised individuals. The frequent usage of classical antimicrobials has begun the increasing emergence of various drug-resistant pathogenic bacterial strains. Hence, this study was intended to evaluate the bioactive seaweed sulfated polysaccharides (SSPs) against the ompF (outer membrane porin F) protein target of Salmonella typhi. SSP is the sulfated compound with a wide range of biological activities, such as anti-microbial, anti-allergy, anti-cancer, anti-coagulant, anti-inflammation, anti-oxidant, and anti-viral. Results In this study, eleven compounds were targeted against S. typhi OmpF by the molecular docking approach and were compared with two commercially available typhoid medications. The SSP showed good binding affinity compared to commercial drugs, particularly carrageenan/MIV-150, carrageenan lambda, fucoidan, and 3-phenyllactate, ranked as top antagonists against OmpF. Further, pharmacokinetics and toxicology (ADMET) studies corroborated that SSP possessed drug-likeness and highly progressed in all parameters. Conclusions AutoDockTools and Schrodinger's QikProp module results suggest that SSP could be a promising drug for extensively drug-resistant (XDR) S. typhi. To the best of our knowledge, this is the first report on in silico analysis of SSP against S. typhi OmpF, thus implying the capabilities of SSPs especially compounds like carrageenans, as a potential anti-microbial agent against Salmonella typhi infections. Eventually, advanced studies could corroborate SSPs to the next level of application in the crisis of XDR microbial diseases. Graphical Abstract

Automated information retrieval and text summarization concept is a difficult process in natural language processing because of the infrequent structure and high complexity of the documents. The text summarization process creates a summary by paraphrasing a long text. Earlier models on information retrieval and summarization are based on a massive labeled dataset by the use of handcrafted features, leveraging on knowledge for a particular domain, and concentrated on the narrow sub-domain to improve efficiency. This paper presents a new deep learning (DL) based information retrieval with a text summarization model. The proposed model involves three major processes namely information retrieval, template generation, and text summarization. Initially, the bidirectional long short term memory (BiLSTM) approach is employed for retrieving the textual data, which assumes each word in a sentence, extracts the information, and embeds it into the semantic vector. Next, the template generation process takes place using the DL model. The deep belief network (DBN) model is employed as a text summarization tool to summarize the textual content. In addition, the image description is generated for the visualized entities that exist in the images. The design of BiLSTM with the DBN model for the text summarization and image captioning process shows the novelty of the work. The performance of the presented method is validated using Giga word corpus and DUC corpus. The experimental results referred that the proposed DBN model outperformed the compared methods with the maximum precision, recall and F-score. The image captions are compared with a predefined set of captions that exists for the image and the performance is evaluated using the BLEU metric.

Purpose: The COVID-19 pandemic imposed challenges to access rehabilitation intervention to individuals with visual impairment, thereby increasing their disability effects. This study explored the viability maintaining the continuum of care through telerehabilitation. Methods: This study is a retrospective analysis of individuals with vision impairment who underwent telerehabilitation at the center of excellence in eye care at Hyderabad, Telangana, India, between April and September 2020. The International Classification of Functioning, Disability and Health framework was followed to provide services such as counseling for mental well-being, information and resources, educational interventions, Assistive Technology programs, therapeutic interventions for children with multiple disabilities, access to digital audio books and rehabilitation helpline. A team of professionals involved in the service care. Phone and what's app calls were used to facilitate the training. The duration and the number of training sessions were individual need-based with an average of 45 minutes per session and 175 training sessions. Results: Three hundred and fifty individuals and their families benefited. The service include early intervention (n = 129), and low vision care (n = 176) inclusive of computer training (n = 53), soft skills (n = 53), digital books (n = 55). Nearly two-thirds of the participants were male (n = 205). Conclusion: Evidence from this study suggests telerehabilitation as a successful model of care. A well-planned telerehabilitation approach can expand the scope of reaching the visually impaired from geographically isolated areas where scarcity of service providers and service centers.

Introduction: Non-communicable diseases (NCDs) have contributed to almost half of the global disease burden. Many countries have experimented with Community Health Volunteers (CHVs) to provide necessary care for NCDs. We aimed at evaluating the contribution of CHVs in mobilizing adults for the Diabetes and Hypertension screening in a selected Primary Health Centre (PHC) of Puducherry, India. Methodology: A community-based operational research study was conducted, where five volunteers from each of the 13 anganwadis functioning under the PHC were chosen as study participants. They were interviewed before enrolment for willingness. Four batches of sensitization and training sessions were conducted to provide the necessary training. CHVs were then given 3 months to mobilize the individuals for NCD screening. This model was evaluated using the Theoretical underpinning technique. Results: Of the total 85 CHVs suggested, around 65 (76.5%) showed willingness for rendering services. Approximately 32 (49.2%) discontinued during the initial weeks of the intervention due to various reasons. The remaining CHVs could reach 363/1470 (24.7%), eligible individuals, among them, 303 (83.5) were convinced to visit the health centre for screening. From the total members who were screened, approximately 52 (17%) and 31 (10%) were diagnosed to have diabetes and hypertension respectively and were initiated on treatment as per national guidelines. Conclusion: About half of the CHVs who volunteered, remained till the end and effectively contributed to a screening of NCDs. The involved volunteers aided in improvising the NCD coverage under the PHC.

Telerehabilitation is a viable option to provide continuum of rehabilitation intervention in situations like the ongoing pandemic. Presently, there is no policy guidelines to the minimum standard of telerehabilitation. This paper describes procedures for telerehabilitation for people with blindness and low vision from the evidence-based practices from a premier eye institute in South India. The suggested guidelines can help develop and replicate similar models of telerehabilitation to reach people in need in difficult situations like COVID 19 pandemic.

Abstract A zinc‐bromine redox flow battery (RFB) is highly suitable for high‐energy storage due to its decoupled energy and power generation. However, the poor kinetics and poor reversible behavior of Br2/Br− redox activity are some of the significant barriers, and as a result, the flow system delivers low power density. To increase the efficiency of the flow cell, in the present work, bimetallic catalysts are deposited on 3D graphite felt network and are used in the positive electrode for enhancing the kinetics of the Br2/Br− redox reaction. The platinum–nickel (PtNi) bimetallic composition is optimized, and the highly improved performances are investigated using half‐cell and flow‐cell assembly. The redox kinetics parameters are improved due to the high electro‐catalytic nature of the heat‐treated Ni‐rich PtNi coating on the graphite felt (GF) and the flow cell is operated up to 140 mA cm−2. The flow cell with Pt0.5Ni1@GF delivers an impressive ever‐best power density of around 1550 mW cm−2. The cycle life shows excellent stability up to 300 cycles with coulombic, voltage, and energy efficiency of 97%, 86%, and 83%, respectively. Thus, the present work offers a promising approach to developing effective electrode materials for obtaining a superpower RFB system.

Summary: Auxilin participates in the uncoating of clathrin-coated vesicles (CCVs), thereby facilitating synaptic vesicle (SV) regeneration at presynaptic sites. Auxilin (DNAJC6/PARK19) loss-of-function mutations cause early-onset Parkinson’s disease (PD). Here, we utilized auxilin knockout (KO) mice to elucidate the mechanisms through which auxilin deficiency and clathrin-uncoating deficits lead to PD. Auxilin KO mice display cardinal features of PD, including progressive motor deficits, α-synuclein pathology, nigral dopaminergic loss, and neuroinflammation. Significantly, treatment with L-DOPA ameliorated motor deficits. Unbiased proteomic and neurochemical analyses of auxilin KO brains indicated dopamine dyshomeostasis. We validated these findings by demonstrating slower dopamine reuptake kinetics in vivo, an effect associated with dopamine transporter misrouting into axonal membrane deformities in the dorsal striatum. Defective SV protein sorting and elevated synaptic autophagy also contribute to ineffective dopamine sequestration and compartmentalization, ultimately leading to neurodegeneration. This study provides insights into how presynaptic endocytosis deficits lead to dopaminergic vulnerability and pathogenesis of PD.

Introduction: Chronic wounds, especially the non healing type, are among the foremost common conditions encountered by a surgeon. Currently, steady research is being pursued on the creation of fancy and indulgent topical growth factors for wound healing. One such agent is phenytoin which has a stimulatory effect on connective tissue. Several studies were conducted worldwide to study the effect of phenytoin on chronic ulcers. However, such studies are lacking in our geographical area. Aim: To compare the efficacy of topical phenytoin dressings with conventional saline dressings in the healing of chronic Diabetic Foot Ulcers (DFUs), in terms of the surface area of ulcer, granulation tissue formation as a percentage of the surface area of ulcer, duration of hospital stay, and side effects. Materials and Methods: This was a longitudinal study that included 100 patients with chronic DFUs admitted to a tertiary care hospital, in North Andhra Pradesh for a period of 1 year. The study population was divided into two groups based on the patient’s willingness for undergoing topical phenytoin therapy. Patients willing to undergo the topical phenytoin dressing therapy formed the study group (n=50) and those who were not willing were subjected to traditional saline dressings, which formed the control group (n=50). The variables of the surface area of the ulcer, granulation tissue formation as a percentage of the surface area of the ulcer, duration of hospital stay, and side effects of topical phenytoin dressings were compared using Paired, and Unpaired Student’s t-test, and the p-value of

Antimicrobial resistance is posing a great threat in many low and middle income countries as a result of groundless and unseemly use of antimicrobial agents in the community. Research related to antimicrobial use, determinants and development of antimicrobial resistance, regional variation and interventional strategies according to the existing health care situation in each country is a big challenge.

The Keap1-Nrf2-ARE pathway is crucial in the antioxidant defense mechanism. The Keap1-Nrf2-ARE pathway has become an important target for the development of potent therapeutic agents for numerous diseases. Keap1-Nrf2 protein inhibitors are electrophilic species that covalently bind with the sulfhydryl group of a cysteine residue of Keap1, which results in modification in cysteine residue. In this in-silico research, we investigated the Keap1 inhibitory potential of 99 quinazoline derivatives by molecular docking investigation. The ligand molecules were extracted from the ZINC15 database in sdf format. The pdb format Keap1 protein with PDBID: 4ZY3 was downloaded from RCSB (https://www.rcsb.org/). Resveratrol was chosen as a standard drug molecule for molecular docking studies to compare the results of test ligands. The in-silico docking study was performed by using AutoDock Vina 1.5.7 software. Out of 99 quinazoline derivatives, 12 derivatives showed the best binding energy towards Keap1. Thus, the top 12 quinazoline derivatives were further screened for their ADME profiling, and bioactivity assessment. The molecular docking study revealed that trifluoromethyl substituted quinazoline derivatives S91 and S44 had the best binding energy of −9.1 kcal/mol and −9.0 kcal/mol respectively (better than reference drug Resveratrol, ΔG = −8.1 kcal/mol) at the KELCH binding pocket of Keap1. Compound S91 formed a conventional hydrogen bond with Val (418, 464,512), Ala (366, 466, 607), and Gly (419,511). All 12 derivatives were found to possess drug likeliness properties. For this result, it can be concluded that quinazoline derivatives can be developed as new potent Keap1-Nrf2 inhibitors. The in-vivo/in-vitro study is necessary to validate the in-silico results.

Colorectal cancer ranks third among all cancers worldwide. Colorectal cancer is treated using a variety of therapies and methods. Almost 1 million deaths are caused every year. The treatment is very ineffective against the cancer cells. Today, drug resistance is a major problem in the fight against cancer. In order to address this, new drugs must be developed. The focus of the article is the synthesis of small molecules of aniline-substituted thieno(2,3-d) pyrimidine derivatives and the evaluation of their anticancer activities. Based on the bioisosterism theory and results from earlier research, thienopyrimidine is substituted with aniline derivatives. Using the HCT116 cell line, the synthesized compounds were tested for cytotoxicity. When compared to standard 5-Fluorouracil (IC50 = 435.59 μg/ml), the compound MS4e has a lower IC50 value (357.12 μg/ml). When aniline was substituted with halogen (F, Cl) cytotoxic properties are observed. It seems to hold special potential for the treatment of colorectal cancer, as the compound MS4e has less IC50 value than the standard.

Background: The primary driving force behind the development of several small molecules for the treatment of tuberculosis is multi-drug resistance. A new fluorinated heterocyclic benzimidazole derivative gives extensive pharmacological activity against the FtsZ protein. FtsZ is a new validated target for tuberculosis drug design. It is a cell division filament protein present in Mycobacterium tuberculosis and other bacteria. Methods: Ligand preparation- The ligand molecules were selected from the previously published paper and analyzed for reliability with the FtsZ protein. The 3D structure of the ligand was prepared using Chem-Draw Pro (version 12.0). Protein preparation- The PDB format FtsZ protein was downloaded from RCSB (https://www.rcsb.org/). The FtsZ protein of PDBID 2q1y was taken for the docking studies. The binding pocket was determined using the Castp server (http://sts.bioe.uic.edu/castp/index.html?201l). Thereafter, the in-silico docking was performed using PyRx 1.0 software. Result: The docking result explains the importance of benzimidazole derivatives as potential FtsZ inhibitors. This study was focused on the in-silico development of new inhibitors and their chances to develop the candidate for oral delivery. The binding free energy, ADMET properties, and druglikeness characteristic of benzimidazole derivatives make them a perfect candidate for FtsZ inhibitors. Compound A-21 and A-20 had the best binding energy of −9.0 kcal/mol and −8.9 kcal/mol respectively. Molecular docking study revealed that Asn41, Thr42, Gly69, and Ala70 are required for conventional hydrogen bonding. The majority of the compounds (A-1, A-23 to A-32) are substrates for P-gp, which implies that their concentration inside the cell remain low due to P-efflux mechanism. Conclusion: Compound A-20 formed five H-bond with target proteins (Gln30, Thr200, Gly226, Asp296, Val305). Almost all the molecules fulfil the criteria of drug likeliness. From this result, it can be concluded that benzimidazole derivatives can be developed as a new anti-Tb agent.

Tuberculosis (TB) is the fastest spreading infectious disease and one of the top ten diseases that kill millions of people annually. The rapid spread of a multidrug-resistant strain of Mycobacterium tuberculosis leads to multidrug-resistance tuberculosis (MDR-TB), which is very difficult to treat. Filament temperature-sensitive protein ring-Z (Ftsz) protein could be the best target to inhibit bacterial cytokinesis. This research is conducted to predict the antitubercular activity of trisubstituted benzimidazole derivatives targeting FtsZ protein by an in-silico approach (molecular docking, pharmacokinetic parameter, drug likeliness, toxicity prediction, and biological activity prediction). Amine and aldehyde substitutions are used as primary scaffolds to design 20 trisubstituted benzimidazole derivatives for molecular docking. AutoDock vina v.1.2.0 software was used to predict the binding interaction between ligand and receptor (FtsZ, PDB ID : 1RQ7). The drug-likeliness properties and toxicity of ligands were predicted from SwissADMET and ToxiM web servers, respectively. Compound A15 (2,3,5,6-tetrafluoro-N1-{6-fluoro-5-[4-(1H-imidazole-1-yl) phenoxy]-1H-1,3-benzodiazol-2-yl} benzene-1,4-diamine) showed the best binding energy (ΔG = −10.2 kcal/mol/) along with four hydrogen bond interactions (GLY107, PHE180, ASP 184). Similarly, compounds A19 and A20 have the best binding score of −9.8 kcal/mol, with excellent pharmacokinetic parameters. It is found that the binding energy of all ligands (ΔG = −8.0 to −10.2 kcal/mol) is better than the reference compound Moxifloxacin (ΔG = −7.7 kcal/mol). None of the ligands violate Lipinski’s rule, but all ligands’ toxicity is slightly high (>0.8 score). It is reported that the amine-substituted benzimidazole derivatives have better binding energy than the aldehyde substitution. Therefore, it is concluded that compounds A19 and A20 can be the best candidate as Ftsz protein inhibitors but an in-vitro animal study and toxicity study are necessary to validate these data.

Abstract Reading requires the correct identification of letters and letter positions within words. Selective attention is, therefore, required to select chunks of the text for sequential processing. Despite the extensive literature on visual attention, the well-known effects of spatial cues in simple perceptual tasks cannot inform us about the role of attention in a task as complex as reading. Here, we systematically manipulate spatial attention in a multi-letter processing task to understand the effects of spatial cues on letter encoding in typical adults. Overall, endogenous (voluntary) cue benefits were larger than exogenous (reflexive). We show that cue benefits are greater in the left than in the right visual field and larger for the most crowded letter positions. Endogenous valid cues reduced errors due to confusing letter positions more than misidentifications, specifically for the most crowded letter positions. Therefore, shifting endogenous attention along a line of text is likely an important mechanism to alleviate the effects of crowding on encoding letters within words. Our results help set the premise for constructing theories about how specific mechanisms of attention support reading development in children. Understanding the link between reading development and attention mechanisms has far-reaching implications for effectively addressing the needs of children with reading disabilities.

Vaccination is the time-tested strategy in controlling the infectious diseases. The global scientific community has agreed upon the role of mass vaccination, as a strategy in abating the ongoing COVID pandemic. By immunizing the at-risk population vaccination aims not only to break the chain of spread of disease but also reduces the severity of the disease, hospitalization, and mortality. In the wake of waning immunity and emerging variants, spreading the world over its time to review the evidence of a third dose as a booster. When deciding on the booster dose, availability of the vaccine, type of vaccine, circulating SARS-CoV-2 variants, and emerging variants have to be taken into consideration. Booster dose as the name suggests boosts the waning immunity of the population and when implemented as a public health measure has the potential to increase the antibody level of the population beyond a threshold, thereby mitigating the spread of COVID infection. Cross-protection is likely to the newly emerging SARS-CoV-2 variants by virtue of the enhanced immune response. However, to develop robust recommendations, investigations on the effectiveness and cost-effectiveness of booster doses vaccines are needed in the context of rapidly spreading variant, the omicron.

BackgroundThe shock-and-kill strategy for HIV cure requires the reactivation of latent HIV followed by the killing of the reactivated cellular reservoir. Galectin-9, an immunomodulatory protein, is shown to induce HIV reactivation as well as contribute to non-AIDS- and AIDS-defining events. The protein is prone to cleavage by inflammatory proteases at its linker region separating the N- and C-terminal carbohydrate-binding domains (N- and C-CRDs) which differ in their binding specificities. It is important to study the activity of its cleaved as well as uncleaved forms in mediating HIV reactivation and immunomodulation in order to understand their role in HIV pathogenesis and their further utilization for the shock-and-kill strategy.MethodologyThe PBMCs of HIV patients on virally suppressive ART (n = 11) were stimulated using 350 nM of the full-length protein and N- and C-CRDs of Gal-9. HIV reactivation was determined by analyzing gag RNA copies using qPCR using isolated CD4 cells and intracellular P24 staining of PBMCs by flow cytometry. Cytokine responses induced by the full-length protein and N- and C-CRDs of Gal-9 were also assessed by flow cytometry, Luminex, and gene expression assays. Changes in T helper cell gene expression pattern after the stimulation were also determined by real-time PCR array.ResultsBoth N- and C-CRDs of galectin-9 induced HIV reactivation in addition to the full-length galectin-9 protein. The two domains elicited higher cytokine responses than the full-length protein, possibly capable of mediating higher perturbations in the immune system if used for HIV reactivation. N-CRD was found to induce the development of Treg cells, whereas C-CRD inhibited the induction of Treg cells. Despite this, both domains elicited IL-10 secretory response although targeting different CD4 cell phenotypes.ConclusionN- and C-CRDs were found to induce HIV reactivation similar to that of the full-length protein, indicating their possible usefulness in the shock-and-kill strategy. The study indicated an anti-inflammatory role of N-CRD versus the proinflammatory properties of C-CRD of galectin-9 in HIV infection.

- With the increase in the number of automobiles in urban cities, the number of accidents has increased manifold. Hence, the need for ambulances is increasing at an alarming rate. In order to increase the survival rates of the patients, an efficient communication of ambulances with the hospital and routing of the ambulances at the signal posts is very essential. Hence, the proposed architecture is distributed in nature. The system not only provides effective communication between the ambulance and the hospital but also helps the ambulance send the signal to nearby traffic signal posts to open up so that the ambulance can easily pass through saving ample amounts of time. The signal posts use a camera to detect the incoming ambulance and open up that lane so that the ambulance need not spend much time waiting for the traffic to get cleared.

BackgroundDigital technologies are widely recognized for their equalizing effect, improving access to affordable health care regardless of gender, ethnicity, socioeconomic status, or geographic region. The Thrive by Five app is designed to promote positive interactions between children and their parents, extended family, and trusted members of the community to support socioemotional and cognitive development in the first 5 years of life and to strengthen connections to culture and community. ObjectiveThis paper aims to describe the iterative co-design process that underpins the development and refinement of Thrive by Five’s features, functions, and content. Minderoo Foundation commissioned this work as a quality improvement activity to support an engaging user experience and inform the development of culturally appropriate and relevant content for parents and caregivers in each country where the app is implemented. MethodsThe app content, referred to as Collective Actions, comprises “The Why,” that presents scientific principles that underpin socioemotional and cognitive development in early childhood. The scientific information is coupled with childrearing activities for parents, extended family, and members of the community to engage in with the children to support their healthy development and to promote positive connections between parents, families, and communities and these young children. Importantly, the initial content is designed and iteratively refined in collaboration with a subject matter expert group from each country (ie, alpha testing). This content is then configured into the app (either a beta version or localized version) for testing (ie, beta testing) by local parents and caregivers as well as experts who are invited to provide their feedback and suggestions for improvements in app content, features, and functions via a brief web-based survey and a series of co-design workshops. The quantitative survey data will be analyzed using descriptive statistics, whereas the analysis of qualitative data from the workshops will follow established thematic techniques. ResultsTo date, the co-design protocol has been completed with subject matter experts, parents, and caregivers from 9 countries, with the first results expected to be published by early 2023. The protocol will be implemented serially in the remaining 21 countries. ConclusionsMobile technologies are the primary means of internet connection in many countries worldwide, which underscores the potential for mobile health programs to improve access to valuable, evidence-based, and previously unavailable parenting information. However, for maximum impact, it is critically important to ensure that mobile health programs are designed in collaboration with the target audience to support the alignment of content with parents’ cultural values and traditions and its relevance to their needs and circumstances. International Registered Report Identifier (IRRID)DERR1-10.2196/39225

Polyphenols are secondary metabolites from plant origin and are shown to possess a wide range of therapeutic benefits. They are also reported as regulators of autophagy, inflammation and neurodegeneration. The autophagy pathway is vital in degrading outdated organelles, proteins and other cellular wastes. The dysregulation of autophagy causes proteinopathies, mitochondrial dysfunction and neuroinflammation thereby contributing to neurodegeneration. Evidence reveals that polyphenols improve autophagy by clearing misfolded proteins in the neurons, suppress neuroinflammation and oxidative stress and also protect from neurodegeneration. This review is an attempt to summarize the mechanism of action of polyphenols in modulating autophagy and their involvement in pathways such as mTOR, AMPK, SIRT-1 and ERK. It is evident that polyphenols cause an increase in the levels of autophagic proteins such as beclin-1, microtubule-associated protein light chain (LC3 I and II), sirtuin 1 (SIRT1), etc. Although it is apparent that polyphenols regulate autophagy, the exact interaction of polyphenols with autophagy markers is not known. These data require further research and will be beneficial in supporting polyphenol supplementation as a potential alternative treatment for regulating autophagy in neurodegenerative diseases.

Background: Mitochondrial dysfunction plays a crucial role in Parkinson’s disease (PD) pathogenesis. The present study was undertaken to investigate the effects of Telmisartan (TEL), an angiotensin II type 1 receptor (AT1R) blocker, on the mitochondria-specific genes expression in a mouse model of Parkinsonism. Materials and methods: Mice were divided into 5 groups with 6 in each; Group I received 0.5% CMC (control) + saline, Group II received 0.5% CMC + 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (positive control), Group III & IV received MPTP + TEL 3 and 10 mg/kg, p.o. respectively, Group V received TEL 10 mg/kg, p.o. (drug control). MPTP was given 80 mg/kg intraperitoneal in two divided doses (40 mg/kg × 2 at 16 h time interval). Vehicle or TEL was administered 1 h before the MPTP injection. Motor function was assessed 48 h after the first dose of MPTP and animals were euthanized to collect brain. Results: Mice intoxicated with MPTP showed locomotor deficits and significant upregulation of α-synuclein (α-syn), downregulation of metastasis-associated protein 1 (MTA1), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in the substantia nigra pars compacta (SNpc) and Striatum (STr) regions of brains. In addition, MPTP intoxication down-regulated mitochondria-specific genes such as DJ-1, PTEN-induced putative kinase 1 (PINK1), Parkin, enriched with leucine repeats kinase 2 (LRRK2) gene expfression. Pre-treatment with TEL restored locomotor functions and upregulated PINK1, Parkin, LRRK2, DJ-1, MTA1 and UCHL1. Conclusion: The present study evidences that TEL has the ability to improve mitochondrial functions in PD.

The lysosomal storage disease cystinosis, caused by cystinosin deficiency, is characterized by cell malfunction, tissue failure, and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis. The impaired LAMP2A trafficking and localization were rescued either by the expression of wild-type cystinosin or by the disease-associated point mutant CTNS-K280R, which has no cystine transporter activity. Defective LAMP2A trafficking in cystinosis was found to associate with decreased expression of the small GTPase Rab11 and the Rab7 effector RILP. Defective Rab11 trafficking in cystinosis was rescued by treatment with small-molecule CMA activators. RILP expression was restored by up-regulation of the transcription factor EB (TFEB), which was down-regulated in cystinosis. Although LAMP2A expression is independent of TFEB, TFEB up-regulation corrected lysosome distribution and lysosomal LAMP2A localization in Ctns-/- cells but not Rab11 defects. The up-regulation of Rab11, Rab7, or RILP, but not its truncated form RILP-C33, rescued LAMP2A-defective trafficking in cystinosis, whereas dominant-negative Rab11 or Rab7 impaired LAMP2A trafficking. Treatment of cystinotic cells with a CMA activator increased LAMP2A localization at the lysosome and increased cell survival. Altogether, we show that LAMP2A trafficking is regulated by cystinosin, Rab11, and RILP and that CMA up-regulation is a potential clinically relevant mechanism to increase cell survival in cystinosis.