Keratin 17 modulates the immune topography of pancreatic cancer.

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. METHODS: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. RESULTS: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations. CONCLUSIONS: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.

Holistic perilous index-based environmental appraisal of Metal(oid)s in the sole coral-bearing island of northeastern bay of Bengal.

This study aimed to evaluate the concentration, distribution, along with the environmental and human health impact of eight heavy metals-Pb, Cr, Cu, Cd, Zn, Mn, Ni, and As-on St. Martin's Island in the northeastern Bay of Bengal, and in doing so to help implement new legislations to protect the island. Focusing on the island's significance as a tourist destination, with seafood being a prominent dietary component, three sample types (sediment, seawater, and crustaceans) were selected for a comprehensive assessment, considering seasonal variations. Concentration of metals was observed to be lower than the established standards in sediment samples, but in seawater samples, Pb, Cr, Cd and Zn were higher than US-EPA values for natural marine water. The metals displayed a decreasing trend of Zn > Ni > Pb > Cu > Mn > As > Cd > Cr in crustacean samples for both seasons. Crustacean samples displayed higher metal concentrations in winter than in monsoon. Pb exceeded the maximum allowable limit for crustaceans with a concentration of about 3 and 4 mg kg-1 in monsoon and winter respectively; being more than 6-8 times the standard for Bangladesh which is only about 0.5 mg kg-1. Health indices displayed that although adults may suffer less from carcinogenic/non-carcinogenic health effects, the risks are far greater for children. For both age groups, As and Ni displayed possibilities of developing cancer. Principal Component Analysis (PCA)shed light on the sources of metals and showed that most of them were from anthropogenic sources. Overall, this study found that the quality of the environment of the island was better in comparison to previous studies made before the pandemic, and so, if the trend continues, it may lead to a better environment for the organisms around the island and help to keep the negative physiological impacts from the consumption of these organisms to a minimal.

Keratin 17 modulates the immune topography of pancreatic cancer.

Background: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival. Methods: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs. Results: K17 expression had profound effects on the exclusion of intratumoral CD8 + T cells and was also associated with decreased numbers of peritumoral CD8 + T cells, CD16 + macrophages, and CD163 + macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8 + T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations. Conclusions: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.

Short Jute Fiber Preform Reinforced Polypropylene Thermoplastic Composite: Experimental Investigation and Its Theoretical Stiffness Prediction.

Natural-based lignocellulose fibrous materials can be used as a sustainable alternative to conventional fossil-based fibers such as glass fibers, in lightweight fiber-reinforced thermoplastic composites for marine, automotive, aerospace, or other advanced applications. However, one of the main challenges in using natural fiber-based thermoplastic composites is the low mechanical performance of composite structures. This can be improved significantly through the development of an optimized novel fiber architecture with enhanced fiber packing properties, following a low-cost production process. In this context, this study demonstrates a less energy-consuming and cheaper manufacturing process, for developing highly individualized short jute fiber-based dry fiber preform architecture, with an improved fiber packing property. Short jute fibers were chemically treated with alkali and PVA sizing treatments in the processing of new fiber preform architectures, and they were used in manufacturing of ultimate short jute fiber/polypropylene (PP) thermoplastic composites. The newly developed short fiber thermoplastic composites showed a significant improvement in mechanical properties (tensile, flexural, and impact) compared to any other natural fiber architecture-based (woven, knitted, nonwoven, unidirectional, etc.) composites found in the literature. Due to the use of new fiber architecture, the developed composites' fiber content was observed to increase. In addition, the compatibility of jute fibers with the polypropylene matrix was strengthened with the application of chemical treatments on highly individualized jute fibers. These reasons were responsible for the enhancement of mechanical properties of developed composites. Micromechanics of the fibers in composites were evaluated using the modified rule of the mixture and Halpin-Tsai equations for stiffness prediction of the composites in order to develop a theoretical understanding of newly developed composites' mechanics. It is thought that the improved mechanical performance of short jute fiber/PP thermoplastic composites can extend the use of these composites in many load-demanding applications, wherein normally synthetic fiber composites are used.

Risk assessment of microplastic pollution in an industrial region of Bangladesh.

Despite the high potential for microplastics (MPs) pollution in Bangladesh, the presence of MPs in the industrial region has largely been unexplored in Bangladesh. So, this study was conducted to determine whether MP pollution is prevalent in the industrial soil of Bangladesh and the extent of its toxicity. To examine MPs, a total of 12 soil samples were collected from the industrial region of Narayanganj, and a stereoscopic microscope was used to visually identify the MPs. Prior to that the technique of density separation and sieving was applied to extract MPs from those 12 soil samples. Among the twelve investigated samples, a total of 151 MPs (Mean: 12.6 ± 7.9 particles kg-1) were identified, which were mostly white and ranged in size from 0.5 to 1 mm. Different types of MPs according to their shapes such as fibers (60.3%), fragments (19.2%), films (10.6%), and foam (9.9%) have been detected. 7 MPs (Mean: 0.58 ± 0.79) have been found in 3 urban farmland sites, 15 MPs (Mean: 1.87 ± 1.81) in two near metropolitan areas, and 129 MPs (Mean: 4.6 ± 4.39) in 7 industrial locations. Five polymers were identified by µ-FTIR, among which Polyamide predominated, followed by Polypropylene. According to risk assessments, the region falls under hazard categories II and III, suggesting a moderate to high risk. This paper gives thorough information on the toxicity of MP in an industrial location; therefore, it may be useful in the development of effective methods to address environmental issues.

Phafins Are More Than Phosphoinositide-Binding Proteins.

Phafins are PH (Pleckstrin Homology) and FYVE (Fab1, YOTB, Vac1, and EEA1) domain-containing proteins. The Phafin protein family is classified into two groups based on their sequence homology and functional similarity: Phafin1 and Phafin2. This protein family is unique because both the PH and FYVE domains bind to phosphatidylinositol 3-phosphate [PtdIns(3)P], a phosphoinositide primarily found in endosomal and lysosomal membranes. Phafin proteins act as PtdIns(3)P effectors in apoptosis, endocytic cargo trafficking, and autophagy. Additionally, Phafin2 is recruited to macropinocytic compartments through coincidence detection of PtdIns(3)P and PtdIns(4)P. Membrane-associated Phafins serve as adaptor proteins that recruit other binding partners. In addition to the phosphoinositide-binding domains, Phafin proteins present a poly aspartic acid motif that regulates membrane binding specificity. In this review, we summarize the involvement of Phafins in several cellular pathways and their potential physiological functions while highlighting the similarities and differences between Phafin1 and Phafin2. Besides, we discuss research perspectives for Phafins.

Evolutionary trend of bovine ß-defensin proteins toward functionality prediction: A domain-based bioinformatics study.

Defensins are small cationic cysteine-rich and amphipathic peptides that form of three-dimensional ß-strand structure connected by disulfide bonds. Defensins form key elements of the innate immune system of multicellular organisms. They not only possess broad-spectrum antimicrobial activity but also have diverse roles, including cell signaling, ion channel agitation, toxic functions, and enzyme inhibitor activities in various animals. Although the role of ß-defensins in immune responses against infectious agents and reproduction could be significant, inadequate genomic information is available to explain the whole ß-defensin repertoire in cattle. No domain or motif-based functional analyses have been previously reported. In addition, how do defensins possess this magnitude of functions in the immune system is still not clear. Our present study, therefore, investigated the sequence divergence and evolutionary relations of bovine defensin proteins with those of humans. Our domain-based evolutionary analysis revealed four major clusters with significant domain variation while reserving a main antimicrobial activity. Our study revealed the ß-defensin domain as the ancestor domain, and it is preserved in the first group of defensin protein with no α-helix in its structure. Due to natural selection, some domains have evolved independently within clusters II and III, while some proteins have lost their domain characteristics. Cluster IV contains the most recently evolved domains. Some proteins of all but cluster I might have adopted the functional characteristics of α-defensins which is largely absent in cattle. The proteins show different patterns of disulfide bridges and multiple signature patterns which might render them specialized functions in different tissue to combat against various pathogens.

Development of an Amorphous Nickel Boride/Manganese Molybdate Heterostructure as an Efficient Electrode Material for a High-Performance Asymmetric Supercapacitor.

The exploration of heterostructure materials with unique electronic properties is considered a desirable platform for fabricating electrode/surface interface relationships for constructing asymmetric supercapacitors (ASCs) with high energy density. In this work, a heterostructure based on amorphous nickel boride (NiXB) and crystalline square bar-like manganese molybdate (MnMoO4) was prepared by a simple synthesis strategy. The formation of the NiXB/MnMoO4 hybrid was confirmed by powder X-ray diffraction (p-XRD), field emission scanning electron microscopy (FE-SEM), field-emission transmission electron microscopy (FE-TEM), Brunauer-Emmett-Teller (BET), Raman, and X-ray photoelectron spectroscopy (XPS). In this hybrid system (NiXB/MnMoO4), the intact combination of NiXB and MnMoO4 leads to a large surface area with open porous channels and abundant crystalline/amorphous interfaces with a tunable electronic structure. This NiXB/MnMoO4 hybrid shows high specific capacitance (587.4 F g-1) at 1 A g-1, and it even retains a capacitance of 442.2 F g-1 at 10 A g-1, indicating superior electrochemical performance. The fabricated NiXB/MnMoO4 hybrid electrode also exhibited an excellent capacity retention of 124.4% (10000 cycles) and a Coulombic efficiency of 99.8% at a current density of 10 A g-1. In addition, the ASC device (NiXB/MnMoO4//activated carbon) achieved a specific capacitance of 104 F g-1 at 1 A g-1 and delivered a high energy density of 32.5 Wh.kg-1 with a power density of 750 W·kg-1. This exceptional electrochemical behavior is due to the ordered porous architecture and the strong synergistic effect of NiXB and MnMoO4, which enhances the accessibility and adsorption of OH- ions that improve electron transport. Moreover, the NiXB/MnMoO4//AC device exhibits excellent cyclic stability with a retention of 83.4% of the original capacitance after 10000 cycles, which is due to the heterojunction layer between NiXB and MnMoO4 that can improve the surface wettability without causing structural changes. Our results show that the metal boride/molybdate-based heterostructure is a new category of high-performance and promising material for the growth of advanced energy storage devices.

Identification of novel inhibitors of high affinity iron permease (FTR1) through implementing pharmacokinetics index to fight against black fungus: An in silico approach.

Mucormycosis is a life-threatening fungal infection, particularly in immunocompromised patients. Mucormycosis has been reported to show resistance to available antifungal drugs and was recently found in COVID-19 as a co-morbidity that demands new classes of drugs. In an attempt to find novel inhibitors against the high-affinity iron permease (FTR1), a novel target having fundamental importance on the pathogenesis of mucormycosis, 11,000 natural compounds were investigated in this study. Virtual screening and molecular docking identified two potent natural compounds [6',7,7,10',10',13'-hexamethylspiro[1,8-dihydropyrano[2,3-g]indole-3,11'-3,13-diazatetracyclo[5.5.2.01,9.03,7]tetradecane]-2,9,14'-trione and 5,7-dihydroxy-3-(2,2,8,8-tetramethylpyrano[2,3-f]chromen-6-yl)chromen-4-one] that effectively bind to the active cavity of FTR1 with a binding affinity of -9.9 kcal/mol. Multiple non-covalent interactions between the compounds and the active residues of this cavity were noticed, which is required for FTR1 inhibition. These compounds were found to have inhibitory nature and meet essential requirements to be drug-like compounds with a considerable absorption, distribution, metabolism, and excretion (ADME) profile with no toxicity probabilities. Molecular dynamics simulation confirms the structural compactness and less conformational variation of the drug-protein complexes maintaining structural stability and rigidity. MM-PBSA and post-simulation analysis predict binding stability of these compounds in the active cavity. This study hypothesizing that these compounds could be a potential inhibitor of FTR1 and will broaden the clinical prospects of mucormycosis.

Pathways Toward a Functional HIV-1 Cure: Balancing Promise and Perils of CRISPR Therapy.

First identified as a viral defense mechanism, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) has been transformed into a gene-editing tool. It now affords promise in the treatment and potential eradication of a range of divergent genetic, cancer, infectious, and degenerative diseases. Adapting CRISPR-Cas into a programmable endonuclease directed guide RNA (gRNA) has attracted international attention. It was recently awarded the 2020 Nobel Prize in Chemistry. The limitations of this technology have also been identified and work has been made in providing potential remedies. For treatment of the human immunodeficiency virus type one (HIV-1), in particular, a CRISPR-Cas9 approach was adapted to target then eliminate latent proviral DNA. To this end, we reviewed the promise and perils of CRISPR-Cas gene-editing strategies for HIV-1 elimination. Obstacles include precise delivery to reservoir tissue and cell sites of latent HIV-1 as well as assay sensitivity and specificity. The detection and consequent excision of common viral strain sequences and the avoidance of off-target activity will serve to facilitate a final goal of HIV-1 DNA elimination and accelerate testing in infected animals ultimately for use in man.

Genomic diversity and molecular dynamics interaction on mutational variances among RB domains of SARS-CoV-2 interplay drug inactivation.

The scientific community has been releasing whole genomic sequences of SARS-CoV-2 to facilitate the investigation of molecular features and evolutionary history. We retrieved 36 genomes of 18 prevalent countries of Asia, Europe and America for genomic diversity and mutational analysis. Besides, we studied mutations in the RBD regions of Spike (S) proteins to analyze the drug efficiency against these mutations. In this research, phylogenenetic analysis, evolutionary modeling, substitution pattern analysis, molecular docking, dynamics simulation, etc. were performed. The genomic sequences showed >99% similarity with the reference sequence of China.TN93 + G was predicted as a best nucleotide substitution model. It was revealed that effective transition from the co-existing SARS genome to the SARS-CoV-2 and a noticeable positive selection in the SARS-CoV-2 genomes occurred. Moreover, three mutations in RBD domain, Val/ Phe367, Val/ Leu 382 and Ala/ Val522, were discovered in the genomes from Netherland, Bangladesh and the USA, respectively. Molecular docking and dynamics study showed RBD with mutation Val/Leu382 had the lowest binding affinity with remdesivir. In conclusion, the SARS-CoV-2 genomes are similar, but multiple degrees of transitions and transversions occurred. The mutations cause a significant conformational change, which are needed to be investigated during drug and vaccine development.

CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination.

BACKGROUND: A barrier to HIV-1 cure rests in the persistence of proviral DNA in infected CD4+ leukocytes. The high HIV-1 mutation rate leads to viral diversity, immune evasion, and consequent antiretroviral drug resistance. While CRISPR-spCas9 can eliminate latent proviral DNA, its efficacy is limited by HIV strain diversity and precision target cell delivery. METHODS: A library of guide RNAs (gRNAs) designed to disrupt five HIV-1 exons (tat1-2/rev1-2/gp41) was constructed. The gRNAs were derived from a conseensus sequence of the transcriptional regulator tat from 4004 HIV-1 strains. Efficacy was affirmed by gRNA cell entry through transfection, electroporation, or by lentivirus or lipid nanoparticle (LNP) delivery. Treated cells were evaluated for viral excision by monitoring HIV-1 DNA, RNA, protein, and progeny virus levels. FINDINGS: Virus was reduced in all transmitted founder strains by 82 and 94% after CRISPR TatDE transfection or lentivirus treatments, respectively. No recorded off-target cleavages were detected. Electroporation of TatDE ribonucleoprotein and delivery of LNP TatDE gRNA and spCas9 mRNA to latently infected cells resulted in up to 100% viral excision. Protection against HIV-1-challenge or induction of virus during latent infection, in primary or transformed CD4+ T cells or monocytes was achieved. We propose that multi-exon gRNA TatDE disruption delivered by LNPs enables translation for animal and human testing. INTERPRETATION: These results provide "proof of concept' for CRISPR gRNA treatments for HIV-1 elimination. The absence of full-length viral DNA by LNP delivery paired with undetectable off-target affirms the importance of payload delivery for effective viral gene editing. FUNDING: The work was supported by the University of Nebraska Foundation, including donations from the Carol Swarts, M.D. Emerging Neuroscience Research Laboratory, the Margaret R. Larson Professorship, and individual donor support from the Frances and Louie Blumkin Foundation and from Harriet Singer. The research received support from National Institutes of Health grants T32 NS105594, 5R01MH121402, 1R01Al158160, R01 DA054535, PO1 DA028555, R01 NS126089, R01 NS36126, PO1 MH64570, P30 MH062261, and 2R01 NS034239.

Insomnia in Bangladeshi Young Adults During the COVID-19 Pandemic: The Role of Behavioral Factors, COVID-19 Risk and Fear, and Mental Health Issues.

BACKGROUND: Given the importance of sleep, several studies were conducted during the first wave of the COVID-19 pandemic in Bangladesh, but no study was conducted during the second wave. Thus, this study assessed the prevalence rate, associated factors, and predictive models of insomnia during the second wave of the COVID-19 pandemic. METHODS: An online-based cross-sectional survey was conducted during the second wave of the pandemic (within April 1-13, 2021) and collected information on sociodemographic, behavior and health, COVID-19 risk, fear of COVID-19, depression, anxiety, suicidality, and insomnia. A total of 756 data from Bangladeshi young adults (22.24 ± 4.39 years) were finally analyzed. RESULTS: About 13% of the participants (n = 98 out of a total of 756) had the symptoms of insomnia. Insomnia had a significant gender difference, where females were more prone to be insomniac. Besides, middle class, urban residence, smoking status, not engaging in physical exercise, poor health status, and multi-comorbidities were also profoundly associated with insomnia. In addition, fear of COVID-19, COVID-19 risk, and mental health problems (i.e., depression, anxiety, and suicidality) showed a significant relationship in terms of insomnia. A total of 31.2% variance predicting insomnia was identified considering all of the studied variables. CONCLUSIONS: The prevalence of insomnia reported herein seems relatively lower than the prior studies, but this figure is not neglectable. Thus, the identified associated factors are highly suggested to consider in policy actions with a special focus on mental health problems to elevate the risk of sleep problems.

Biodegradation of salicylic acid, acetaminophen and ibuprofen by bacteria collected from a full-scale drinking water biofilter.

This study examined the biodegradation of two pharmaceuticals-acetaminophen, and ibuprofen, and one natural organic surrogate-salicylic acid, by bacteria seeded from backwash water collected from a full-scale biofiltration plant. The degradation was studied in the presence of oxygen. Complete removal of salicylic acid was observed in 27-66 h depending on the seasonality of the collected backwash water, while 90-92% acetaminophen removal was observed in more than 225 h. Ibuprofen demonstrated poor removal efficiencies with only 50% biodegradation after 230 h. Adenosine tri phosphate (ATP) in the reactor was found to be linked with the biodegradation rate. ATP was found to be correlated with oxygen uptake rate (OUR). ATP also had a correlation with each of extracellular polymeric substances (EPS), protein and polysaccharides. These results highlight the potential for increasing the biodegradation rates to achieve enhanced contaminant removal.

Humanized Mice for Infectious and Neurodegenerative disorders.

Humanized mice model human disease and as such are used commonly for research studies of infectious, degenerative and cancer disorders. Recent models also reflect hematopoiesis, natural immunity, neurobiology, and molecular pathways that influence disease pathobiology. A spectrum of immunodeficient mouse strains permit long-lived human progenitor cell engraftments. The presence of both innate and adaptive immunity enables high levels of human hematolymphoid reconstitution with cell susceptibility to a broad range of microbial infections. These mice also facilitate investigations of human pathobiology, natural disease processes and therapeutic efficacy in a broad spectrum of human disorders. However, a bridge between humans and mice requires a complete understanding of pathogen dose, co-morbidities, disease progression, environment, and genetics which can be mirrored in these mice. These must be considered for understanding of microbial susceptibility, prevention, and disease progression. With known common limitations for access to human tissues, evaluation of metabolic and physiological changes and limitations in large animal numbers, studies in mice prove important in planning human clinical trials. To these ends, this review serves to outline how humanized mice can be used in viral and pharmacologic research emphasizing both current and future studies of viral and neurodegenerative diseases. In all, humanized mouse provides cost-effective, high throughput studies of infection or degeneration in natural pathogen host cells, and the ability to test transmission and eradication of disease.

Identification and host response interaction study of SARS-CoV-2 encoded miRNA-like sequences: an in silico approach.

COVID-19, a global pandemic caused by an RNA virus named SARS-CoV-2 has brought the world to a standstill in terms of infectivity, casualty, and commercial plummet. RNA viruses can encode microRNAs (miRNAs) capable of modulating host gene expression, and with that notion, we aimed to predict viral miRNA like sequences of MERS-CoV, SARS-CoV and SARS-CoV-2, analyze sequence reciprocity and investigate SARS-CoV-2 encoded potential miRNA-human genes interaction using bioinformatics tools. In this study, we retrieved 206 SARS-CoV-2 genomes, executed phylogenetic analysis, and the selected reference genome (MT434792.1) exhibited about 99% similarities among the retrieved genomes. We predicted 402, 137, and 85 putative miRNAs of MERS-CoV (NC_019843.3), SARS-CoV (NC_004718.3), and SARS-CoV-2 (MT434792.1) genome, respectively. Sequence similarity was analyzed among 624 miRNAs which revealed that the predicted miRNAs of SARS-CoV-2 share a cluster with the clad of miRNAs from MERS-CoV and SARS-CoV. Only SARS-CoV-2 derived 85 miRNAs were encountered for target prediction and 29 viral miRNAs seemed to target 119 human genes. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis suggested the involvement of respective genes in various pathways and biological processes. Finally, we focused on eight putative miRNAs influencing 14 genes that are involved in the adaptive hypoxic response, neuroinvasion and hormonal regulation, and tumorigenic progression in patients with COVID-19. SARS-CoV-2 encoded miRNAs may cause misexpression of some critical regulators and facilitate viral neuroinvasion, altered hormonal axis, and tumorigenic events in the human host. However, these propositions need validation from future studies.

In silico identification of conserved miRNAs in the genome of fibre biogenesis crop Corchorus capsularis.

Corchorus capsularis, commonly known as jute occupies the leading position in the production of natural fibre alongside lower environmental threat. Small noncoding ~21 to 24 nucleotides long microRNAs play significant roles in regulating the gene expression as well as different functions in cellular growth and development. Here, the study adopted a comprehensive in silico approach to identify and characterize the conserved miRNAs in the genome of C. capsularis including functional annotation of specific gene targets. Expressed Sequence Tags (ESTs) based homology search of 3350 known miRNAs of dicotyledons were allowed against 763 non-redundant ESTs of jute genome, resulted in the prediction of 5 potential miRNA candidates belonging five different miRNA families (miR1536, miR9567-3p, miR4391, miR11300, and miR8689). The putative miRNAs were composed of 18 nucleotides having a range of -0.49 to -1.56 MFEI values and 55%-61% of (A + U) content in their pre-miRNAs. A total of 1052 gene targets of putative miRNAs were identified and their functions were extensively analyzed. Most of the gene targets were involved in plant growth, cell cycle regulation, organelle synthesis, developmental process and environmental responses. Five gene targets, namely, NAC Domain Containing Protein, WRKY DNA binding protein, 3-dehydroquinate synthase, S-adenosyl-L-Met-dependent methyl transferase and Vascular-related NAC-Domain were found to be involved in the lignin biosynthesis, phenylpropanoid pathways and secondary wall formation. The present study might accelerate the more miRNA discovery, strengthening the complete understanding of miRNAs association in the cellular basis of lignin biosynthesis towards the production of high standard jute products.

Genome based evolutionary lineage of SARS-CoV-2 towards the development of novel chimeric vaccine.

The present study aimed to predict a novel chimeric vaccine by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein, membrane protein, envelope protein and nucleocapsid protein were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and normal mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. However, the in vivo and in vitro validation of suggested vaccine molecule might be ensured with wet lab trials using model animals for the implementation of the presented data.

Ancestral origin, antigenic resemblance and epidemiological insights of novel coronavirus (SARS-CoV-2): Global burden and Bangladesh perspective.

SARS-CoV-2, a new coronavirus strain responsible for COVID-19, has emerged in Wuhan City, China, and continuing its global pandemic nature. The availability of the complete gene sequences of the virus helps to know about the origin and molecular characteristics of this virus. In the present study, we performed bioinformatic analysis of the available gene sequence data of SARS-CoV-2 for the understanding of evolution and molecular characteristics and immunogenic resemblance of the circulating viruses. Phylogenetic analysis was performed for four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings demonstrated that SARS-CoV-2 exhibited convergent evolutionary relation with previously reported SARS-CoV. It was also depicted that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed a lower level of resemblance. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. Descriptive epidemiological analysis on several epidemiological indices was performed on available epidemiological outbreak information from several open databases on COVID-19 (SARS-CoV-2). Satellite-derived imaging data have been employed to understand the role of temperature in the environmental persistence of the virus. Findings of the descriptive analysis were used to describe the global impact of newly emerged SARS-CoV-2, and the risk of an epidemic in Bangladesh.

Bullying victimization and adverse health behaviors among school-going adolescents in South Asia: Findings from the global school-based student health survey.

BACKGROUND: Bullying among adolescents is a global public health issue and has adverse behavioral and mental health consequences, yet a little is known about the relationship between bullying victimization and adverse health behaviors in adolescence in South Asian countries. METHODS: Data for this cross-sectional analysis were extracted from the global school-based student health survey (GSHS) in Bangladesh (n = 2,989), 2014 and in Nepal (n = 6,529), 2015. Multivariate logistic regression analyses were used to identify the associations between bullying victimization and adverse health behaviors or outcomes: physical violence, sexual history, tobacco use, alcohol use, drug use, suicide ideation, plan, attempt, loneliness, and sleeping difficulty. RESULTS: The prevalence of bullying victimization that occurred for a minimum of 1 day during the 30 days preceding the survey was 24.5% in Bangladesh and 50.9% in Nepal. This study observed significant relationships between bullying victimization and several adverse health behaviors/outcomes. For example, in Bangladesh, the odds of attempted suicide were found to be higher in adolescents that experienced bullying for 1-2 (adjusted odds ratio [AOR]: 2.92; 95% confidence interval [CI]: 1.64-5.19), 3-5 (AOR: 3.55; 95% CI: 1.69), 6-9 (AOR: 5.33; 95% CI: 1.24-22.77), or 10 days or more (AOR: 9.83; 95% CI: 4.17-23.16) during the 30 days preceding the survey than who did not. CONCLUSIONS: Bullying among adolescents in school is common in Bangladesh and Nepal and is associated with several adverse health behaviors. Bullying and its potential health consequences are needed to be addressed in health promotion and programs in these countries.