WHAT IS A CRO?

The industry has one of the smartest workforce and most come to work with passion in their bones, whether it be in their first job or those positions that followed. [...]when all players cooperatively work together as a team with common goals, it is a winwin for society at large. According to its website, "In 1947, a young veterinarian purchased one thousand rat cages from a Virginia farm and set up a one-man laboratory in Boston, overlooking the Charles River. In other words, it is not uncommon for a CRO to provide scientific, clinical, and business continuity for pharmaceutical company sponsors. [...]to maximize the CRO's contribution to the overall development programs, the CRO should become an active member of the team.

Prospects of lassa fever candidate vaccines

Background: Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far. Materials and Methods: We reviewed the progress made on twenty-six vaccine candidates listed by Salami et al. (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/. Results: Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine;both had progressed to clinical trials. Conclusions: Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.

Evaluation of expression and titration of recombinant nucleocapsid protein as an immunogenic candidate against SARS-CoV2

Introduction: Covid-19 epidemic results from an infection caused by SARS-CoV2. Evolution-based analyses on the nucleotide sequences show that SARS-CoV2 is a member of the genus Beta-coronaviruses and its genome consists of a single-stranded RNA, encoding 16 proteins. Among the structural proteins, the nucleocapsid is the most abundant protein in virus structure, highly immunogenic, with sequence conservatory. Due to a large number of mutations in the spike protein, the aim of this study was to investigate bioinformatics, expression of nucleocapsid protein and evaluate its immunogenicity as an immunogenic candidate. Materials and Methods: B and T cell epitopes of nucleocapsid protein were examined in the IEDB database. The PET28a-N plasmid was transferred to E. coli BL21(DE3) expression host, and IPTG induced recombinant protein expression. The protein was purified using Ni-NTA column affinity chromatography, and the Western blotting method was utilized to confirm it. Finally, mice were immunized with three routes of purified protein. Statistical analysis of the control group injection and test results was carried out by t-test from SPSS software. Results: The optimized gene had a Codon adaptation index (CAI) of 0/97 Percentage of codons having high- frequency distribution was improved to 85%. Expression of recombinant protein in E. coli led to the production of BoNT/B-HCC with a molecular weight of 45 kDa. The total yield of purified protein was 43 mg/L. Immunization of mice induced serum antibody response. Statistical analysis showed that the antibody titer ratio was significantly different compared to the control sample and the antibody titer was acceptable up to a dilution of 1.256000. Conclusion: According to the present study results, the protein can be used as an immunogenic candidate for developing vaccines against SARS-CoV2 in future research.

Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research. (Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research.)

This special issue contains 23 articles that discuss various aspects of antiviral research, focusing on the contributions and legacy of Dr. Mike Bray, the retiring Editor-in-Chief of Antiviral Research. The articles cover a range of topics, including the underappreciated mouse model for Ebola virus disease, the history and impact of the mouse-adapted Ebola virus model, and the characterisation of CD-1 mice infected with different strains of Ebola virus. Other articles delve into transplacental vertical transmission of flaviviruses, the development of reverse genetic systems for SARS-CoV-2, and the mechanisms of action and drug resistance of nucleotide analogues against the virus. The special issue also explores therapeutics for flaviviral infections, alternative splicing in RNA virus infections, and targeted protein degradation as an antiviral approach.

International Conference on "Biotechnological Interventions to Overcome Challenges of Covid/post-Covid Era-2022" (BIOCoPE-2022), Rajasthan, India, 24-25 March 2022

This journal issue includes 31 articles that discuss salt stress in plants and amelioration strategies;algal biorefinery;in-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2;development of an effective strategy using green synthesized nanoparticles;effect of methyl jasmonate in enhanced growth, antioxidants and reduced Pb uptake in contrasting cluster bean cultivars;biosynthesis of silver nanoparticles using mushroom extract and its toxicity assessement in zebrafish embryos;phytogenic synthesis of metallic nanoparticles;abiotic stress responses and strategies of microbes mediated mitigation for sustainable agriculture.

A Combined Method Based on the FIPV N Monoclonal Antibody Immunofluorescence Assay and RT-nPCR Method for the Rapid Diagnosis of FIP-Suspected Ascites

Feline infectious peritonitis (FIP), which is caused by feline infectious peritonitis virus (FIPV), is a fatal and immunologically mediated infectious disease among cats. At present, due to the atypical clinical symptoms and clinicopathological changes, the clinical diagnosis of FIP is still difficult. The gold standard method for the differential diagnosis of FIP is immunohistochemistry (IHC) which is time-consuming and requires specialized personnel and equipment. Therefore, a rapid and accurate clinical diagnostic method for FIPV infection is still urgently needed. In this study, based on the etiological investigation of FIPV in parts of southern China, we attempted to explore a new rapid and highly sensitive method for clinical diagnosis. The results of the etiological investigation showed that the N gene of the FIPV BS8 strain had the highest homology with other strains. Based on this, a specific FIPV BS8 N protein monoclonal antibody was successfully prepared by expression of the recombinant proteins, immunization of mice, fusion and selection of hybridoma cell lines, and screening and purification of monoclonal antibodies. Furthermore, we carried out a time-saving combination method including indirect immunofluorescence assay (IFA) and nested reverse transcription polymerase chain reaction (RT-nPCR) to examine FIP-suspected clinical samples. These results were 100% consistent with IHC. The results revealed that the combined method could be a rapid and accurate application in the diagnosis of suspected FIPV infection within 24 hours. In conclusion, the combination of IFA and RT-nPCR was shown to be a fast and reliable method for clinical FIPV diagnosis. This study will provide insight into the exploitation of FIPV N antibodies for the clinical diagnosis of FIP-suspected ascites samples.

The possibility of using perfluorocarbon compounds for virus-associated pneumonia treatment

The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed - gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the last-the beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this category's treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique.

The Importance of Animal Models in Biomedical Research: Current Insights and Applications.

Animal research is considered a key element in advance of biomedical science. Although its use is controversial and raises ethical challenges, the contribution of animal models in medicine is essential for understanding the physiopathology and novel treatment alternatives for several animal and human diseases. Current pandemics' pathology, such as the 2019 Coronavirus disease, has been studied in primate, rodent, and porcine models to recognize infection routes and develop therapeutic protocols. Worldwide issues such as diabetes, obesity, neurological disorders, pain, rehabilitation medicine, and surgical techniques require studying the process in different animal species before testing them on humans. Due to their relevance, this article aims to discuss the importance of animal models in diverse lines of biomedical research by analyzing the contributions of the various species utilized in science over the past five years about key topics concerning human and animal health.

SARS-CoV-2 Variant Pathogenesis Following Primary Infection and Reinfection in Syrian Hamsters.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has evolved into multiple variants. Animal models are important to understand variant pathogenesis, particularly for variants with mutations that have significant phenotypic or epidemiological effects. Here, cohorts of naive or previously infected Syrian hamsters (Mesocricetus auratus) were infected with variants to investigate viral pathogenesis and disease protection. Naive hamsters infected with SARS-CoV-2 variants had consistent clinical outcomes, tissue viral titers, and pathology, while hamsters that recovered from initial infection and were reinfected demonstrated less severe clinical disease and lung pathology than their naive counterparts. Males had more frequent clinical signs than females in most variant groups, but few sex variations in tissue viral titers and lung pathology were observed. These findings support the use of Syrian hamsters as a SARS-CoV-2 model and highlight the importance of considering sex differences when using this species. IMPORTANCE With the continued circulation and emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, understanding differences in the effects between the initial infection and a subsequent reinfection on disease pathogenesis is critical and highly relevant. This study characterizes Syrian hamsters as an animal model to study reinfection with SARS-CoV-2. Previous infection reduced the disease severity of reinfection with different SARS-CoV-2 variants.

HOW THE PANDEMIC PUT BAT IMMUNOLOGY IN THE SPOTLIGHT

Foo, who manages the colony and is affiliated with Duke-National University of Singapore (Duke-NUS) Medical School, and Yroy, a veterinary technician at SingHealth Experimental Medicine Centre, have nurtured the bats for years. The colonywas set up by Lin-fa Wang, a virologist at Duke-NUS Medical School to create a controlled setting for studying bat biology, including the inner workings of their immune system. Attendance at talks and conferences about bats is rising - at one symposium hosted last year in the United States, there were 30% more participants compared with the same event organized before the pandemic - and funders are ploughing money into studies of bats and infectious diseases: in 2021, for instance, both China and the United States announced specific funding pots for research into bats and viruses. The latest research is filling in details of the biological mechanisms underpinning the bat immune response, including the identification of cell types that are potentially unique to bats1.

Continuous Glucose Monitoring in Hypoxic Environments Based on Water Splitting-Assisted Electrocatalysis

Conventional enzyme-based continuous glucose sensors in interstitial fluid usually rely on dissolved oxygen as the electron-transfer mediator to bring electrons from oxidase to electrode while generating hydrogen peroxide. This may lead to several problems. First, the sensor may provide biased detection results owing to fluctuation of oxygen in interstitial fluid. Second, the polymer coatings that regulate the glucose/oxygen ratio can affect the dynamic response of the sensor. Third, the glucose oxidation reaction continuously produces corrosive hydrogen peroxide, which may compromise the long-term stability of the sensor. Here, we introduce an oxygen-independent nonenzymatic glucose sensor based on water splitting-assisted electrocatalysis for continuous glucose monitoring. For the water splitting reaction (i.e., hydrogen evolution reaction), a negative pretreatment potential is applied to produce a localized alkaline condition at the surface of the working electrode for subsequent nonenzymatic electrocatalytic oxidation of glucose. The reaction process does not require the participation of oxygen;therefore, the problems caused by oxygen can be avoided. The nonenzymatic sensor exhibits acceptable sensitivity, reliability, and biocompatibility for continuous glucose monitoring in hypoxic environments, as shown by the in vitro and in vivo measurements. Therefore, we believe that it is a promising technique for continuous glucose monitoring, especially for clinically hypoxic patients.

Optimization of high protein and zinc composite flour formulation with response surface methodology

Covid-19 pandemic had limited people's movement despite the demand to remain productive and maintain good health. Therefore, it was necessary to provide foods which are easy to distribute, durable, nutritious, and easily transformable to increase immunity. This research aims to develop a composite flour (TK) formula with optimal proportion of wheat flour (TT), snakehead fish flour (TIG), pumpkin flour (TBuL), and pumpkin seed flour (TBiL) which then enriched with zinc. The resulting TK is expected to be used as an ingredient for nutritious snacks containing high protein and zinc. The research was conducted in four stages, namely the making of each constituent flour, determining the best formulation with the Response Surface Methodology using Central Composite Design model, characterizing the physicochemical properties of TK and making meatballs, biscuits, and unting-unting from the TK. The three products were tested on experimental animals for their metabolic responses. The optimization of the formula resulted in three optimal formulations, namely formula A, B, and C with the proportion of TT:TIG:TBuL:TBiL respectively as follows 55:20:15:10;56.65:20:13.35:10;57.98:20:12.02:10. The most optimal formula of composite flour was formula A with the highest protein (26.12%) and zinc (18.06 mg/kg) content among other formulas. Then, zinc was added into Formula A using microencapsulation, and TK with protein content of 26.74% and zinc of 56.8 mg/kg were obtained. The histopatology observation on experimental animals showed that the three products made from TK did not cause necrosis of the liver or cell infiltration in the kidneys.

Special Issue: Mutagenic factors in the environment impacting human and animal health. (Special Issue: Mutagenic factors in the environment impacting human and animal health.)

This special issue includes 15 articles that discuss the mutagenic effect of tobacco smoke on male fertility;environmental and occupational exposure of metals and female reproductive health;free radical biology in neurological manifestations;paternal factors in recurrent pregnancy loss;mechanical dependency of the SARS-CoV-2 virus and the renin-angiotensin-aldosterone (RAAS) axis;a perspective review on medicinal plant resources for their antimutagenic potentials;asystematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones;impact of ginseng on neurotoxicity induced by cisplatin in rats.

VPAgs-Dataset4ML: A Dataset to Predict Viral Protective Antigens for Machine Learning-Based Reverse Vaccinology

Reverse vaccinology (RV) is a computer-aided approach for vaccine development that identifies a subset of pathogen proteins as protective antigens (PAgs) or potential vaccine candidates. Machine learning (ML)-based RV is promising, but requires a dataset of PAgs (positives) and non-protective protein sequences (negatives). This study aimed to create an ML dataset, VPAgs-Dataset4ML, to predict viral PAgs based on PAgs obtained from Protegen. We performed seven steps to identify PAgs from the Protegen website and non-protective protein sequences from Universal Protein Resource (UniProt). The seven steps included downloading viral PAgs from Protegen, performing quality checks on PAgs using the standard BLASTp identity check ≤30% via MMseqs2, and computational steps running on Google Colaboratory and the Ubuntu terminal to retrieve and perform quality checks (similar to the PAgs) on non-protective protein sequences as negatives from UniProt. VPAgs-Dataset4ML contains 2145 viral protein sequences, with 210 PAgs in positive.fasta and 1935 non-protective protein sequences in negative.fasta. This dataset can be used to train ML models to predict antigens for various viral pathogens with the aim of developing effective vaccines.Dataset: https://doi.org/10.17632/w78tyrjz4z.1Dataset License: CC BY 4.0

Ocular manifestations of COVID-19 infection

The eyes, which were not previously the subject of investigation, have emerged as one of the more intriguing aspect of COVID-19 infection. The probable pathways for SARS-CoV-2 infection through the eyes are either through the tear film and draining tear ducts leading to the upper respiratory tract and gastrointestinal tract, or through the conjunctiva into limbal superficial cells into the inner eye, where distribution via the blood or nervous system appears to be possible. Virus pathogenesis through tear and conjunctiva has been established in animal models of several coronavirus eye diseases, and preliminary research have shown that SARS-CoV-2 may do the same in humans. Given that COVID-19 cases have reached pandemic proportions and are on the rise, it is vital to recognize the illness's ocular manifestations and avert potentially vision-threatening effects. Coronaviruses may be transmitted between animals and humans through evolution, therefore investigating them in animal models could be crucial in the future to discover further elements of ocular involvement. It is recommended that health care and individual personnel take steps to avoid infection and limit viral transmission. More study is needed to understand the transmission pathways and the alternatives for COVID-19 prevention and therapy disseminated through the ocular surfaces for prompt recovery of the patients.

Obesity and the brain. Winter Conference 2021, 7-8 December 2021

This journal issue includes 48 articles that discuss development and validation of a novel quality assessment tool to measure the quality of nutrition information online;longitudinal association between takeaway food environment and secondary school adolescents BMI and body fat percentage;dietary practices, beliefs, and behaviours among adults with inflammatory bowel disease;postpartum depression in Irish mothers and associations with infant feeding practices;the impact of dietary saturated fat replacement with unsaturated fat on the plasma lipidome and cardiometabolic disease risk;ole of brain serotonin in age-related decline in physical activity in mice;ey stakeholder perceptions of food allergies within the airline industry;sleep quality of higher education students during COVID-19 and its association with diet quality and lifestyle behaviours.

Effects of different mucosal adjuvants on the immune responses induced by porcine deltacoronavirus in mice

Objective: The aim of this study is to screen an ideal adjuvant for an inactivated porcine deltacoronavirus(PDCoV) vaccine to induce mucosal immunity and reduce the side effect of the vaccine. We used different mucosal adjuvants to prepare the inactivated PDCoV vaccines. We then used mouse model to evaluate the humoral, cellular and mucosal immune responses induced by the inactivated vaccines via different immunization routes.

New evidence for aerosol transmission of SARS-CoV-2

Since the outbreak of COVID-19, the opinion that the aerosol plays a key role in the transmission of SARS-CoV-2 has been controversial. The COVID-19 pandemic has continued interpersonal transmission for more than two years, especially after the emergence of Delta and Omicron variants, making the situation of COVID-19 pandemic more severe. The transmission of SARS-COV-2 variants was significantly accelerated and the time of transmission between generations was significantly shortened. Therefore, it has been questioned to attribute the close-range infection to droplet transmission. The point that the aerosol can also has a close-range transmission and may play a dominant role is neglected under the influence of traditional transmission mode of respiratory infectious diseases. A large number of studies have shown that normal breath, talk and cough could release a large number of respiratory aerosol particles, and the virus particles were mainly tiny particles(=5.0 micro m). The biological activity and infectivity of the droplet nuclei have been questioned in the studies on their physicochemical properties. Animal models of ferrets and hamsters showed that SARS-COV-2 could transmit via aerosol. Therefore, the new evidence for the aerosol transmission of SARS-COV-2 was reviewed in the article so as to provide latest evidence-based evidence for prevention and control of COVID-19.

Safety of the live at attenuated vaccine avishield IB GI-13 against infectious bronchitis in SPF chickens during laying period

Avian infectious bronchitis (IB) is an economically important, highly contagious, acute disease of Chickens caused by a single-stranded positive RNA Virus that belongs to the Coronaviridae family. The Virus can replicate in the oviduct and cause permanent damage in young hens resulting in the false layer occurrence. In laying hens, infectious bronchitis Virus (IBV) infections can cause a severe decline in egg production and a number of effects on egg quality and reduced hatchability. The most effective means of controlling IB in poultry is vaccination. In the areas with increased pressure of circulating field challenge Virus, live attenuated vaccines are also used during the laying period with the intention of keeping local protection of the respiratory tract at a high level. The vaccine strain IB V-173/11 contained in Avishield IB GI-13 vaccine is a strain that genetically (S1 gene) belongs to GI-13 lineage and antigenically to 793B IBV serotype. Viral infections of this serotype occur frequently in Europe and therefore most vaccination programs in broilers, layers and breeders along a live IBV vaccine of the Massachusetts serotype also include a live vaccine of the 793B serotype, GI-I3 lineage. In this paper, results of a safety evaluation of live attenuated IB vaccine strain V-173/11, when administered by spray method in a ten-fold maximum dose repeated by one maximum dose in 28-week-old specific pathogen free (SPF) layer Chickens are presented. As a control, non-vaccinated SPF layer chickens were included in the study. The vaccine is considered to be safe when used in laying period because no vaccinated chicken showed abnormal local or systemic reactions or signs of IB related disease, no chicken died from the causes attributable to the vaccine, egg quality was not altered, and there was no statistically significant difference in. egg production between the vaccinated and non-vaccinated group.

Progress of research on COVID-19 animal models

OBJECTIVE: COVID-19 continues to spread globally, which poses a significant threat to global public health security. Recently, the emergence of new variant strains of SARS-CoV-2 complicates the containment of COVID-19 due to its rapid transmission, high infectivity, high viral load, atypical symptoms and high number of severe cases. In order to further understand the transmission route, pathogenesis and pathological changes of COVID-19, and accelerate the research and development of antiviral drugs and vaccines, animal models of COVID-19 have played an important role in this process. The status of research on different animal models of COVID-19 was reviewed, the characteristics were compared among the models so as to provide theoretical basis for selecting appropriate animal models of COVID-19.