Two years of SARS-CoV-2 infection (2019–2021): structural biology, vaccination, and current global situation

The deadly SARS-CoV-2 virus has infected more than 259,502,031 confirmed cases with 5,183,003 deaths in 223 countries during the last 22 months (Dec 2019–Nov 2021), whereas approximately 7,702,859,718, vaccine doses have been administered (WHO: https://covid19.who.int/) as of the 24th of Nov 2021. Recent announcements of test trial completion of several new vaccines resulted in the launching of immunization for the common person around the globe highlighting a ray of hope to cope with this infection. Meanwhile, genetic variations in SARS-CoV-2 and third layer of infection spread in numerous countries emerged as a stronger prototype than the parental. New and parental SARS-CoV-2 strains appeared as a risk factor for other pre-existing diseases like cancer, diabetes, neurological disorders, kidney, liver, heart, and eye injury. This situation requires more attention and re-structuring of the currently developed vaccines and/or drugs against SARS-CoV-2 infection. Although a decline in COVID-19 infection has been reported globally, an increase in COVID-19 cases in the subcontinent and east Mediterranean area could be alarming. In this review, we have summarized the current information about the SARS-CoV-2 biology, its interaction and possible infection pathways within the host, epidemiology, risk factors, economic collapse, and possible vaccine and drug development.

Biologisation of production and technological processes in nursery farming

We conducted a retrospective analysis of national scientific and technological advances by technological design to manifest the demand for organisation processes remodelling towards the methods and approaches of the sixth design, especially in biotechnology. The article defines terms such as nursery, biologisation, promising technology and resource conservation. We analyse the fruit crop seedling production and structure of nursery-specific processes. We determine the main agrocenotic components most susceptible to chemical and technogenic impacts. Studies of soil fertility and biota prioritised the challenge of declined soil activity and biogenicity. We establish that an increased chemical pressure on fruit nursery agrocenoses leads to disturbances in benign microflora, microbiotic, acaro- and entomosystems, alters plant infection pathways and immune status. We report destructive manifestations of microbiotic, entomo- and acarosystems in agrocenoses via the emergence of new pathogenic fungal species, root rotting agents, vascular system necroses (tracheomycoses), resistant typically dominant pathogen strains, higher pathogenicity, the expansion of species list and ranges of bacterial communities, phytoplasmas, viruses and viroids, a more aggressive invasion of new pests, including stem pathogens, emerging hazardous adaptations in economically impactive phytophages. Furthermore, we consider the scientific and practical issues in fruit crop reproduction: sweeping off forms (genotypes) from selection, changes in infection pathways in candidate parental plants, reduced “plant — external environment” adaptation, impaired plant immunity under climatic and anthropogenic stress, selection of candidates with a higher production value under environmental stress burden, reduction of best-quality planting stock, seedling root system retardation, massive crown invasion with fungal and bacterial agents, inadequacy of trait databasing for promising varieties and genotyping techniques. The priority role of agrocenotic biologisation in sustainable fruit nursery is substantiated through adopting modern approaches, especially in biotechnology, based on molecular biology, biochemistry and genetic engineering.

Microbial and Molecular Differences According To The Location of Head and Neck Cancers

Background Microbiome has been shown to substantially contribute to some cancers. However, the diagnostic implications of microbiome in head and neck squamous cell carcinoma (HNSCC) remain unknown. Here, we report for the first time, the molecular difference in the microbiome of oral and non-oral HNSCC. Methods Primary data was downloaded from the Kraken-TCGA dataset. The molecular differences in the microbiome of oral and non-oral HNSCC were identified using the linear discriminant analysis effect size method. Using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUST) and ANOVA-like differential expression (ALDEx2), we predicted bacterial metabolic contributions of oral rich and non-oral rich bacteria, common rich bacteria in two groups and their pathways. A Correlation analysis was performed between RNA expression data and common bacteria data and protein-protein interaction (PPI) analysis was performed using correlated genes. Finally, to find out unique microbial signatures, we performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene ontology (GO) analysis using the PPI results. Results The common microbiomes in oral and non-oral cancers were Fusobacterium, Treponema, and Selenomonas and Clostridium and Massilia, respectively. We found unique microbial signatures that positively and negatively correlated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in oral cancer and negatively correlated KEGG pathways in non-oral cancer. In oral cancer, positively correlated genes were mostly found in bacterial infection pathways, while negative correlated genes were involved in HTLV-I infection, signal transduction, cell adhesion, and cancer-associated pathway. In non-oral cancer, positively correlated genes did not show any significant results, and negatively correlated genes showed results from focal adhesion pathway and regulation of actin cytoskeleton pathway. Conclusions These results could help in understanding the underlying biological mechanisms of the microbiome of oral and non-oral HNSCC. Microbiome-based oncology diagnostic tool warrants further exploration.

Effects of Temperature and Wetness Duration on Infection by Coniella diplodiella, the Fungus Causing White Rot of Grape Berries

Grapevine white rot, caused by Coniella diplodiella, can severely damage berries during ripening. The effects of temperature and wetness duration on the infection severity of C. diplodiella were investigated by artificially inoculating grape berries through via infection pathways (uninjured and injured berries, and through pedicels). The effect of temperature on incubation was also studied, as was that of inoculum dose. Injured berries were affected sooner than uninjured berries, even though 100% of the berries inoculated with C. diplodiella conidia became rotted whether injured or not; infection through pedicels was less severe. On injured berries, the disease increased as the inoculum dose increased. Irrespective of the infection pathway, 1 h of wetness was sufficient to cause infection at any temperature tested (10–35 °C); with the optimal temperature being 23.8 °C. The length of incubation was shorter for injured berries than for uninjured ones, and was shorter at 25–35 °C than at lower temperatures; the shortest incubation period was 14 h for injured berries at 30 °C. Mathematical equations were developed that fit the data, with R2 = 0.93 for infection through any infection pathway, and R2 = 0.98 for incubation on injured berries, which could be used to predict infection period and, therefore, to schedule fungicide applications.

The Microbiome Profile In Ulcerative Colitis And Pouchitis

Both ulcerative colitis and pouchitis are associated with an imbalance in the intestinal microbiota, which may be related to the immune response. The objective was to determine the bacterial composition in pouchitis and ulcerative colitis in order to explore the underlying pathogenesis. Microbiome was profiled and evaluated by 16S ribosomal DNA gene sequencing in stool samples of 37 patients with ulcerative colitis, 15 patients with normal ulcerative colitis-pouch, 15 patients with ulcerative colitis-pouchitis and 18 healthy volunteers, PICRUSt and PICRUSt2 were performed to analyze the function of dominant bacteria. In our Chinese cohort, with aggravation of ulcerative colitis, intestinal microorganisms were characterized by a gradual decreased in diversity and numbers of butyrate-producing bacteria and Bacteroides. Besides, in addition to the decrease of probiotics, the bloom of Escherichia-Shigella and Ruminococcus_gnavus was observed in pouchitis which related to multiple infection pathways according to KEEG pathway analysis. Our results showed that pouchitis and ulcerative colitis differ in their intestinal microbial structures and metabolic pathways, but the reasons need to be further explored.

Using Mobile Phone Data to Estimate the Relationship between Population Flow and Influenza Infection Pathways

This study aimed to analyze population flow using global positioning system (GPS) location data and evaluate influenza infection pathways by determining the relationship between population flow and the number of drugs sold at pharmacies. Neural collective graphical models (NCGMs; Iwata and Shimizu 2019) were applied for 25 cell areas, each measuring 10 × 10 km2, in Osaka, Kyoto, Nara, and Hyogo prefectures to estimate population flow. An NCGM uses a neural network to incorporate the spatiotemporal dependency issue and reduce the estimated parameters. The prescription peaks between several cells with high population flow showed a high correlation with a delay of one to two days or with a seven-day time-lag. It was observed that not much population flows from one cell to the outside area on weekdays. This observation may have been due to geographical features and undeveloped transportation networks. The number of prescriptions for anti-influenza drugs in that cell remained low during the observation period. The present results indicate that influenza did not spread to areas with undeveloped traffic networks, and the peak number of drug prescriptions arrived with a time lag of several days in areas with a high amount of area-to-area movement due to commuting.

3D Bioprinting for fabrication of tissue models of COVID-19 infection

Over the last few decades, the world has witnessed multiple viral pandemics, the current severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic being the worst and most devastating one, claiming millions of lives worldwide. Physicians, scientists, and engineers worldwide have joined hands in dealing with the current situation at an impressive speed and efficiency. One of the major reasons for the delay in response is our limited understanding of the mechanism of action and individual effects of the virus on different tissues and organs. Advances in 3D bioprinting have opened up a whole new area to explore and utilize the technology in fabricating models of these tissues and organs, recapitulating in vivo environment. These biomimetic models can not only be utilized in learning the infection pathways and drug toxicology studies but also minimize the need for animal models and shorten the time span for human clinical trials. The current review aims to integrate the existing developments in bioprinting techniques, and their implementation to develop tissue models, which has implications for SARS-CoV-2 infection. Future translation of these models has also been discussed with respect to the pandemic.

Staff–pupil SARS-CoV-2 infection pathways in schools in Wales: a population-level linked data approach

BackgroundBetter understanding of the role that children and school staff play in the transmission of SARS-CoV-2 is essential to guide policy development on controlling infection while minimising disruption to children’s education and well-being.MethodsOur national e-cohort (n=464531) study used anonymised linked data for pupils, staff and associated households linked via educational settings in Wales. We estimated the odds of testing positive for SARS-CoV-2 infection for staff and pupils over the period August– December 2020, dependent on measures of recent exposure to known cases linked to their educational settings.ResultsThe total number of cases in a school was not associated with a subsequent increase in the odds of testing positive (staff OR per case: 0.92, 95% CI 0.85 to 1.00; pupil OR per case: 0.98, 95% CI 0.93 to 1.02). Among pupils, the number of recent cases within the same year group was significantly associated with subsequent increased odds of testing positive (OR per case: 1.12, 95% CI 1.08 to 1.15). These effects were adjusted for a range of demographic covariates, and in particular any known cases within the same household, which had the strongest association with testing positive (staff OR: 39.86, 95% CI 35.01 to 45.38; pupil OR: 9.39, 95% CI 8.94 to 9.88).ConclusionsIn a national school cohort, the odds of staff testing positive for SARS-CoV-2 infection were not significantly increased in the 14-day period after case detection in the school. However, pupils were found to be at increased odds, following cases appearing within their own year group, where most of their contacts occur. Strong mitigation measures over the whole of the study period may have reduced wider spread within the school environment.

Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8–12 weeks (young) or 45–55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

Paediatric Common Infections Pathways: improving antimicrobial stewardship and promoting ambulation for children presenting with common infections to hospitals in the UK and Ireland

Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital. The pathways focus on diagnostic approaches, including the recognition of red flags suggesting complex or severe infection requiring urgent intervention, approaches to antimicrobial stewardship (AMS) principles and guidance on safe and timely ambulation aligned with good practice of outpatient parenteral antimicrobial therapy (OPAT).