Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches.

An excessive amount of multidrug-resistant Staphylococcus aureus is commonly associated with actinic keratosis (AK) and squamous cell carcinoma (SCC) by secreted virulence products that induced the chronic inflammation leading to skin cancer which is regulated by staphylococcal accessory regulator (SarA). It is worth noting that there is currently no existing published study that reports on the inhibitory activity of phytochemicals derived from Santalum album on the SarA protein through in silico approach. Therefore, our study has been designed to find the potential inhibitors of S. aureus SarA protein from S. album-derived phytochemicals. The molecular docking study was performed targeting the SarA protein of S. aureus, and CID:5280441, CID:162350, and CID: 5281675 compounds showed the highest binding energy with -9.4 kcal/mol, -9.0 kcal/mol, and -8.6 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period whereas the MMPBSA binding free energy proposed that the ligands were sustained with their binding site. All three complexes were found to be similar in distribution with the apoprotein through PCA analysis indicating conformational stability throughout the MD simulation. Moreover, all three compounds' ADMET profiles revealed positive results, and the AMES test did not show any toxicity whereas the pharmacophore study also indicates a closer match between the pharmacophore model and the compounds. After comprehensive in silico studies we evolved three best compounds, namely, Vitexin, Isovitexin, and Orientin, which were conducted in vitro assay for further confirmation of their inhibitory activity and results exhibited all of these compounds showed strong inhibitory activity against S. aureus. The overall result suggests that these compounds could be used as a natural lead to inhibit the pathogenesis of S. aureus and antibiotic therapy for S. aureus-associated skin cancer in humans as well.

Biochemical and molecular docking-based strategies of Acalypha indica and Boerhavia diffusa extract by targeting bacterial strains and cancer proteins.

Antibiotic-resistant microbes have emerged around the world, presenting a risk to health. Plant-derived drugs have become a potential source for the production of antibiotic-resistant drugs and cancer therapies. In this study, we investigated the antibacterial, cytotoxic and antioxidant properties of Acalypha indica and Boerhavia diffusa, and conducted in silico molecular docking experiments against EGFR and VEGFR-2 proteins. The metabolic extract of A. indica inhibited Streptococcus iniae and Staphylococcus sciuri with inhibition zones of 21.66 ± 0.57 mm and 20.33 ± 0.57 mm, respectively. The B. diffusa leaf extract produced inhibition zones of 20.3333 ± 0.5773 mm and 20.33 ± 0.57 mm against Streptococcus iniae and Edwardsiella anguillarum, respectively. A. indica and B. diffusa extracts had toxicities of 162.01 µg/ml and 175.6 µg/ml, respectively. Moreover, B. diffusa (IC50 =154.42 µg/ml) leaf extract exhibited moderately higher antioxidant activity compared with the A. indica (IC50 = 218.97 µg/ml) leaf extract. Multiple interactions were observed at Leu694, Met769 and Leu820 sites for EGFR and at Asp1046 and Cys1045 sites for VEGFR during the molecular docking study. CID-235030, CID-70825 and CID-156619353 had binding energies of -7.6 kJ/mol, -7.5 kJ/mol and -7.6 kJ/mol, respectively, with EGFR protein. VEGFR-2 protein had docking energies of -7.5 kJ/mol, -7.6 kJ/mol and -7.3 kJ/mol, respectively, for CID-6420353, CID-156619353 and CID-70825 compounds. The MD simulation trajectories revealed the hit compound; CID-235030 and EGFR complex, CID-6420353 and VEGFR-2 exhibit stable profile in the root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bond and root mean square fluctuation (RMSF) and the binding free energy by MM-PBSA method. This study indicates that methanol extracts of A. indica and B. diffusa may play a crucial role in developing antibiotic-resistant and cancer drugs.Communicated by Ramaswamy H. Sarma.

Molecular docking and dynamics simulation approach of Camellia sinensis leaf extract derived compounds as potential cholinesterase inhibitors.

The tea plant (Camellia sinensis) belongs to the family Theaceae and contains many phytochemicals that are effective against various diseases, including neurodegenerative disorders. In this study, we aimed to characterize the phytochemicals present in the methanolic and n-hexane leaf extracts of C. sinensis using GC-MS, FTIR, and UV-visible analysis. We detected a total of 19 compounds of different chemical classes. We also performed molecular docking studies using the GC-MS detected phytochemicals, targeting acetylcholinesterase (AChE, PBD ID: 4BDT) and butyrylcholinesterase (BChE, PDB ID: 6QAB), which are responsible for the breakdown of the neurotransmitter acetylcholine (ACh). This breakdown leads to dementia and cognitive decline in Alzheimer's patients. The compounds Ergosta-7,22-dien-3-ol, (3.beta.,5.alpha.,22E)- and Benzene, 1,3-bis(1,1-dimethylethyl) showed better binding affinity against AChE, while dl-.alpha.-Tocopherol and Ergosta-7,22-dien-3-ol, (3.beta.,5.alpha.,22E)- showed better binding affinity against BChE. We determined the stability and rigidity of these best docked complexes through molecular dynamics simulation for a period of 100 ns. All complexes showed stability in terms of SASA, Rg, and hydrogen bonds, but some variations were found in the RMSD values. Our ADMET analysis revealed that all lead compounds are non-toxic. Therefore, these compounds could be potential inhibitors of AChE and BChE.

DTLCx: An Improved ResNet Architecture to Classify Normal and Conventional Pneumonia Cases from COVID-19 Instances with Grad-CAM-Based Superimposed Visualization Utilizing Chest X-ray Images.

COVID-19 is a severe respiratory contagious disease that has now spread all over the world. COVID-19 has terribly impacted public health, daily lives and the global economy. Although some developed countries have advanced well in detecting and bearing this coronavirus, most developing countries are having difficulty in detecting COVID-19 cases for the mass population. In many countries, there is a scarcity of COVID-19 testing kits and other resources due to the increasing rate of COVID-19 infections. Therefore, this deficit of testing resources and the increasing figure of daily cases encouraged us to improve a deep learning model to aid clinicians, radiologists and provide timely assistance to patients. In this article, an efficient deep learning-based model to detect COVID-19 cases that utilizes a chest X-ray images dataset has been proposed and investigated. The proposed model is developed based on ResNet50V2 architecture. The base architecture of ResNet50V2 is concatenated with six extra layers to make the model more robust and efficient. Finally, a Grad-CAM-based discriminative localization is used to readily interpret the detection of radiological images. Two datasets were gathered from different sources that are publicly available with class labels: normal, confirmed COVID-19, bacterial pneumonia and viral pneumonia cases. Our proposed model obtained a comprehensive accuracy of 99.51% for four-class cases (COVID-19/normal/bacterial pneumonia/viral pneumonia) on Dataset-2, 96.52% for the cases with three classes (normal/ COVID-19/bacterial pneumonia) and 99.13% for the cases with two classes (COVID-19/normal) on Dataset-1. The accuracy level of the proposed model might motivate radiologists to rapidly detect and diagnose COVID-19 cases.

An online observational study assessing clinical characteristics and impacts of the COVID-19 pandemic on mental health: a perspective study from Bangladesh.

Purpose: The pandemic of coronavirus disease 2019 (COVID-19) has cost numerous lives and induced tremendous mental stress among people. The purpose of this research was to determine anxiety and depression levels, clinical features, and the connections between demographic variables and depression prevalence as well as anxiety prevalence among reported COVID-19 cases in Bangladesh. Methods: For the purpose of data collection, an online cross-sectional survey was carried out from May 26 to June 27, 2020, utilizing a Google adapted preformed questionnaire. The form was shared with a short overview and justification through Facebook, Twitter, Facebook messenger, Viber, and What's App. The Google form contains five parts: a brief introduction, an approval statement, demographics, clinical and radiological data, and mental health assessment by the Generalized Anxiety Disorder 7-item (GAD-7) scale and Patient Health Questionnaire (PHQ-9). Formal ethical clearance was taken from the Institute of Biological Science (IBSc), Bangladesh. Informed consent was ensured before participation. Results: One hundred and fifty-three (153) patients with COVID-19 who had an average age of 39.43 ± 17.59 years with male predominance (72%) were included. A total of 32.7% were doing health-care related jobs, and 17.7% lost their jobs due to COVID-19. Patients had a median income of 30,000 Bangladesh taka (BDT). Of all, 12.4% of the participants showed asymptomatic features, whereas 87.6% of patients were symptomatic and presented with fever (79%), cough (58.8%), myalgia (24.2%), breathlessness (23.5%), sore throat (21.6%), fatigue (19.6%), headache (13.7%), nausea and/or vomiting (11.8%), runny nose (9.8%), chest pain (9.2%), diarrhea (8.5%), stuffy nose (3.2%), ARDS (2.6%), oral ulcer (2.6%), and conjunctivitis (1.9%). Overall, the prevalence of anxiety and depression was 63.5% and 56.6%, respectively. Among the participants, 13.2% had only anxiety, 6.3% had only depression, and 50.3% had both. Conclusion: In most cases, middle age, male, and healthy workers were patients. Fever and cough were the standard presentations. Approximately two-thirds or 66.67% of patients had anxiety and depression, one or both.

Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays.

Adenanthera pavonina is a medicinal plant with numerous potential secondary metabolites showing a significant level of antidiabetic activity. The objective of the current study was to identify potential phytochemicals from the methanolic leaf extract of Adenanthera pavonina as therapeutic agents against diabetes mellitus using GC-MS and in silico methods. The GC-MS analysis of the leaf extract revealed a total of 17 phytochemicals. Molecular docking was performed using these phytochemicals, targeting the mutated insulin receptor tyrosine kinase (5hhw), which inhibits glucose uptake by cells. Diazoprogesterone (-9.2 kcal/mol), 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid (-6.9 kcal/mol), and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] (-6.6 kcal/mol) exhibited better binding with the target protein. The ADMET analysis was performed for the top three compounds with the best docking scores, which showed positive results with no observed toxicity in the AMES test. Furthermore, the molecular dynamics study confirmed the favorable binding of Diazoprogesterone, 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] with the receptor throughout the 100 ns simulation period.

Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study.

The spread of the Dengue virus over the world, as well as multiple outbreaks of different serotypes, has resulted in a large number of deaths and a medical emergency, as no viable medications to treat Dengue virus patients have yet been found. In this paper, we provide an in silico virtual screening and molecular dynamics-based analysis to uncover efficient Dengue infection inhibitors. Based on a Google search and literature mining, a large phytochemical library was generated and employed as ligand molecules. In this investigation, the protein target NS2B/NS3 from Dengue was employed, and around 27 compounds were evaluated in a docking study. Phellodendroside (-63 kcal/mole), quercimeritrin (-59.5 kcal/mole), and quercetin-7-O-rutinoside (-54.1 kcal/mole) were chosen based on their binding free energy in MM-GBSA. The tested compounds generated numerous interactions at Lys74, Asn152, and Gln167 residues in the active regions of NS2B/NS3, which is needed for the protein's inhibition. As a result, the stable mode of docked complexes is defined by various descriptors from molecular dynamics simulations, such as RMSD, SASA, Rg, RMSF, and hydrogen bond. The pharmacological properties of the compounds were also investigated, and no toxicity was found in computational ADMET properties calculations. As a result, this computational analysis may aid fellow researchers in developing innovative Dengue virus inhibitors.

MirrorME: implementation of an IoT based smart mirror through facial recognition and personalized information recommendation algorithm.

We are living in the era of the fourth industrial revolution, which also treated as 4IR or Industry 4.0. Generally, 4IR considered as the mixture of robotics, artificial intelligence (AI), quantum computing, the Internet of Things (IoT) and other frontier technologies. It is obvious that nowadays a plethora of smart devices is providing services to make the daily life of humans easier. However, in the morning most people around the globe use a traditional mirror while preparing themselves for daily tasks. The aim is to build a low-cost intelligent mirror system that can display a variety of details based on user recommendations. Therefore, in this article, Internet of Things (IoT) and AI-based smart mirror is introduced that will support the users to receive the necessary daily update of weather information, date, time, calendar, to-do list, updated news headlines, traffic updates, COVID-19 cases status and so on. Moreover, a face detection method also implemented with the smart mirror to construct the architecture more secure. Our proposed MirrorME application provides a success rate of nearly 87% in interacting with the features of face recognition and voice input. The mirror is capable of delivering multimedia facilities while maintaining high levels of security within the device.

Clinical manifestations and socio-demographic status of COVID-19 patients during the second-wave of pandemic: A Bangladeshi experience.

BACKGROUND: Bangladesh is a densely populated country with a substandard healthcare system and a mediocre economic framework. Due to the enormous number of people who have been unaware until now, the development of COVID-19's second-wave infection has become a severe threat. The present investigation aimed to characterize the clinical and socio-demographic characteristics of COVID-19 in Bangladesh. METHODS: A cross-sectional analysis was carried out from all the other COVID-19 patients and confirmed by RT-PCR undergoing a specialized COVID-19 hospital. From March 1 to April 15, 2021, a total of 1326 samples were collected. Samples were only obtained from non-critical COVID-19 patients as critically ill patients required emergency intensive care medications. Then, from April 17 to May 03, 2021, SARS-CoV-2 infection and clinical assessment was performed based on interim guidelines from the WHO. The diagnosis was conducted through RT-PCR. Later, identifying the symptomatic and asymptomatic patient based on checking the Clinical Observation Form (COF). The patients filled the COF form. Finally, statistical analyses were done using the SPSS 20 statistical program. RESULTS: In this investigation, a total of 326 patients were diagnosed as COVID-19 positive. Among them, approximately 19.02% (n = 62) were asymptomatic, and 80.98% (n = 264) were symptomatic. Here, the finding shows that the occurrence of this infection was varied depending on age, sex, residence, occupation, smoking habit, comorbidities, etc. However, Males (60.12%) were more affected than females (39.88%), and, surprisingly, this pandemic infected both urban and rural residents almost equally (urban = 50.92%; rural = 49.08%). Approximately 19% of the asymptomatic and 62% of symptomatic cases had at least one comorbid disorder. Interestingly, an unexpected result was exhibited in the case of smokers, where non-smokers were more affected than smokers. The study indicates community transmission of COVID 19, where people were highly infected at their occupations (35.58%), at houses (23.93%) and by traveling (12.88%). Noteworthy, according to this report, a large number (19.33%) of individuals did not know exactly how they were contaminated with SARS-CoV-2. Patients were most commonly treated by an antibiotic 95.09%, followed in second by corticosteroid 46.01%. Anti-viral drugs, remdesivir, and oxygenation are also needed for other patients. Among those, who were being treated, approximately 69.33% were isolated at home, 27.91% were being treated at dedicated COVID-19 hospitals. Finally, 96.63% were discharged without complications, and 0.03% has died. CONCLUSION: This investigation concludes that males became more infected than females. Interestingly, both urban and rural people became nearly equally infected. It noticed community transmission of SARS-CoV-2, where people were highly infected at their workplaces. A higher rate of silent transmission indicates that more caution is needed to identify asymptomatic patients. Most of the infected people were isolated at home whereas nearly one-fourth were treated at hospitals. Clinically, antibiotics were the most widely used treatment. However, the majority of the patients were discharged without complications. The current investigation would be helpful to understand the clinical manifestations and socio-demographic situations during the second wave of the COVID-19 pandemic in Bangladesh.

Targeting SARS-CoV-2 nonstructural protein 15 endoribonuclease: an in silico perspective.

The newly emerged human coronavirus, SARS-CoV-2, had begun to spread last year and sparked worldwide. In this study, molecular docking is utilized to test some previously approved drugs against the SARS-CoV-2 nonstructural protein 15 (Nsp15). We screened 23 drugs, from which three (saquinavir, valrubicin and aprepitant) show a paramount predicted binding affinity (-9.1, -9.6 and -9.2 kcal/mol, respectively) against SARS-CoV-2 Nsp15. Moreover, saquinavir and aprepitant make nonbonded interactions with Leu201 in the active site cavity of Nsp15, while the drug valrubicin interacts with Arg199 and Leu201. This binding pattern may be effective against the targeted protein, leading to Nsp15 blockage and virus abolition. Additionally, the pharmacological properties of the screened drugs are known since they have been approved against different viruses.

Computational discovery of plant-based inhibitors against human carbonic anhydrase IX and molecular dynamics simulation.

Carbonic anhydrase IX (hCAIX) is a membrane-spanning metalloenzyme, encoded by CA9 gene, which can lead to various carcinomas if upregulated. Due to its overexpression in many cancer tissues, hCAIX has become a promising target for developing anticancer therapeutics. Furthermore, several classes of small-molecules have shown to inhibit the hCAIX expression. In this study, therefore, we screened (n = 42) plant-derived compounds to identify the most potent hCAIX inhibitors and to understand their interactions with hCAIX and drug candidacy through in silico approaches. Among all, only three compounds (i.e. fraxoside, scopolin, and xanthone,) provided higher binding affinity toward hCAIX protein as compared to the native ligand. In standard docking, scopolin showed -4.97 kcal/mol of binding energy with hCAIX while control ligand provided -4.45 kcal/mol. In precise docking, the highest binding affinity was found for fraxoside (-7.67 kcal/mol) as compared to -3.04 kcal/mol of the control. The Gibbs free energy (ΔG) of these potent leads was also consistent and in support of the docking studies. The binding interactions were also found to be stable in dynamics simulation. Furthermore, analysis of protein-protein interactions and co-expression revealed the possible association of CA9 gene with other tumorous genes, especially angiogenesis factor HIF1A which will most likely be affected by the identified inhibitors. With further experimental validation, therefore, these potential inhibitors could be effective against hCAIX protein, thereby, paving the way for prospective anticancer therapeutics.Communicated by Ramaswamy H. Sarma.

Investigation of mechanisms involved in seed germination enhancement, enzymatic activity and seedling growth of rice (Oryza Sativa L.) using LPDBD (Ar+Air) plasma.

The study investigates the effect of LPDBD (Low Pressure Dielectric Barrier Discharge) (Ar + Air) plasma on seed germination, seedling growth and antioxidant enzyme activity of rice. Rice seeds were treated with LPDBD (Ar + Air) plasma for 2min, 4min, 6min, 8min and 10min. Seed germination rate, seedling growth, total chlorophyll content, enzymatic activity, total soluble sugar and protein concentration were increased in plants grown from the LPDBD (Ar + Air) plasma treated seeds. It was observed that the sprouting of seeds and the growth of seedlings of rice depends on the feed gases used to generate plasma and plasma processing time. In the case of plantlets germinated from the plasma-treated seeds of rice, the H2O2 level was increased significantly both in leaves and roots for 6min, 8min and 10min treatment respectively. No significant change was observed in Nitric Oxide (NO) concentration in seed, leaf, or root of plants grown from LPDBD (Ar + Air) plasma-treated seeds. The amount of total soluble sugar and protein increased significantly in the case of 2min, 4min, 6min, 8min and 10min seed treatment. Although plants exhibited no significant increase in APX activities, but a significant increase of CAT and SOD activity in the leaf and root was found. This study reveals that LPDBD (Ar + Air) plasma is involved in the elevation of ROS species in leaf and root of rice plants which is tightly regulated by the upregulation of CAT activity that ultimately enhances the seed germination and growth of rice plantlets.

Regulation of the neural niche by the soluble molecule Akhirin.

Though the adult central nervous system has been considered a comparatively static tissue with little turnover, it is well established today that new neural cells are generated throughout life. Neural stem/progenitor cells (NS/PCs) can self-renew and generate all types of neural cells. The proliferation of NS/PCs, and differentiation and fate determination of PCs are regulated by extrinsic factors such as growth factors, neurotrophins, and morphogens. Although several extrinsic factors that influence neurogenesis have already been reported, little is known about the role of soluble molecules in neural niche regulation. In this review, we will introduce the soluble molecule Akhirin and discuss its role in the eye and spinal cord during development.

Tsukushi expression is dependent on Notch signaling and oscillated in the presomitic mesoderm during chick somitogenesis.

During somitogenesis, segmentation of the body axis occurs by epithelial somites budding off from the rostral end of the unsegmented presomitic mesoderm (PSM), and its molecular regulation is achieved by a molecular oscillator and signaling molecules. Tsukushi (TSK) is a unique secreted protein and involved in diverse biological cascades in vertebrate embryos by modulating several signaling pathways at the extracellular region. However, the involvement of TSK in somitogenesis remains unknown. In this study, we investigated the detailed expression patterns of TSK at different developmental stages of a chick embryo. Chick-TSK (C-TSK) is expressed in the PSM and shows an oscillation pattern with three phases. The oscillation pattern of C-TSK in the PSM is similar to that of c-Notch1 and c-hairy1, but not to c-Delta1. Our in vitro data showed that Notch signaling is necessary for the normal expression of C-TSK and that expression of C-TSK is an intrinsic property of the anterior PSM. These data suggest that TSK plays a role in chick somitogenesis.