This study focuses on cardiovascular effects, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students from two schools aged 13–18 years who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms.We enrolled 314 participants; of these, 13 participants were lost to follow up, leaving 301 participants for analysis. The most common cardiovascular effects were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular effects were found in 29.24% of patients, ranging from tachycardia, palpitation, and myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. Conclusion: Cardiovascular effects in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myocarditis. The clinical presentation of myopericarditis after vaccination was usually mild, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for side effects. Clinical Trial Registration: NCT05288231

The coronavirus pandemic was declared by the World Health Organization (WHO) in 2020, and a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, many countries around the world have reported that so-called genetic vaccines, such as those using modified mRNA encoding the spike protein and lipid nanoparticles as the drug delivery system, have resulted in post-vaccination thrombosis and subsequent cardiovascular damage, as well as a wide variety of diseases involving all organs and systems, including the nervous system. In this article, based on these circumstances and the volume of evidence that has recently come to light, we call the attention of medical professionals to the various risks associated with blood transfusions using blood products derived from people who have suffered from long COVID and from genetic vaccine recipients, including those who have received mRNA vaccines, and we make proposals regarding specific tests, testing methods, and regulations to deal with these risks. We expect that this proposal will serve as a basis for discussion on how to address post-vaccination syndrome and its consequences following these genetic vaccination programs.

With COVID-19 vaccines slowly being rolled out in many countries, it is important to understand the public’s acceptance of being vaccinated. This study aims to study the willingness and motivations among residents of the cities of Caloocan, Malabon, and Navotas, Philippines to be vaccinated against COVID-19. Based on an online survey of 137 respondents, who willingly participated in the study, 71% will take a COVID-19 vaccine if it becomes available, with similar rates among respondents from Caloocan (82%), Malabon (83 %), and Navotas (81%). If a vaccine is proven safe and effective, more respondents (82%) will take a COVID-19 vaccine. Furthermore, safety against COVID-19 as well as the safety and effectiveness of vaccines are the primary factors why respondents are willing or unwilling to get a vaccine. The results highlight the need for effective messaging that promotes COVID-19 vaccination, with emphasis on the safety and effectiveness of the vaccine, and its benefits to the public, especially that the vaccines that will be delivered in the country in the next few months are not the most preferred brands by the respondents.

The analysis reported here is unique in that it is the first study of the original data from the Pfizer/BioNTech BNT162b2 mRNA vaccine clinical trial (CA4591001) to be carried out by a group unaffiliated with the trial sponsor. Our study is a forensic analysis of the 38 trial subjects who died between July 27, 2020, the start of Phase 2/3 of the clinical trial, and March 13, 2021, the data end date of their 6-Month Interim Report. Phase 2/3 of the trial involved 44,060 subjects who were equally distributed into two groups and received Dose 1 of either the BNT162b2 mRNA vaccinated or the Placebo control (0.9% normal saline). At Week 20, when the BNT162b2 mRNA vaccine received Emergency Use Authorization from the U.S. FDA, subjects in the placebo arm were given the option to be BNT162b2 vaccinated. All but a few accepted. Surprisingly, a comparison of the number of subject deaths per week during the 33 Weeks of this study found no significant difference between the number of deaths in the vaccinated versus placebo arms for the first 20 weeks of the trial, the placebo-controlled portion of the trial. After Week 20, as subjects in the Placebo were unblinded and vaccinated, deaths among this still unvaccinated cohort of this group slowed and eventually plateaued. Deaths in the BNT162b2 vaccinated subjects continued at the same rate. Our analysis revealed inconsistencies between the subject data listed in the 6-Month Interim Report and publications authored by Pfizer/BioNTech trial site administrators. Most importantly, we found evidence of an over 3.7-fold increase in number of deaths due to cardiovascular events in BNT162b2 vaccinated subjects compared to Placebo controls. This significant adverse event signal was not reported by Pfizer/BioNTech. Potential sources of these data inconsistencies are identified.

This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.

In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4⁺ and CD8⁺ T cell immune response with increased efficiency due to the presence of CD4⁺ and CD8⁺ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This review summarizes the evidence on strategies that can be applied to treat both long and vaccine injuries based on similar mechanisms of action.

The recent outbreak of the new virus in Wuhan city, China from the sea food market has led to the identification of a new strain called the corona virus and named as novel corona virus (2019-nCoV) belonging to Coronaviridae family. This has created major havoc and concern due to the mortality of 250 persons and affecting more than 10,000 people. This virus causes sudden fever, pneumonia and also kidney failure. In this study a computational approach is proposed for drug and vaccine design. The spike protein sequences were collected from a protein database and analysed with various bioinformatics tools to identify suitable natural inhibitors for the N-terminal receptor binding domain of spike protein. Also, it is attempted to identify suitable vaccine candidates by identifying B-Cell and T-cell epitopes. In the drug design, the tanshinone Iia and methyl Tanshinonate were identified as natural inhibitors based on the docking score. In the vaccine design, B-cell epitope VLLPLVSSQCVNLTTRTQLPPAYTN was found to have the highest antigenicity. FVFLVLLPL of MHC class-I allele and FVFLVLLPL of MHC class-II allele were identified as best peptides based on a number of alleles and antigencity scores. The present study identifies natural inhibitors and putative antigenic epitopes which may be useful as effective drug and vaccine candidates for the eradication of novel corona virus.

ABSTRACT. In this paper, we suggest a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions. This method is used to evaluate then compare the spike genes related to the main SARS-CoV2 VARIANTS currently circulating within the world population. The 10 main results proposed to be reproduced by peers are: 1/ SARS-CoV2 genome and spike evolution in one year 2020-2021. 2/ SARS-CoV2 Origins. 3/ Comparing 11 reference variants spikes. 4/ analysing 32 CAL.20C California variant patients spikes. 5/ Toward a meta mRNA Fibonacci gene end message code. 6/ Analysing S501 UK, S484 South Africa and « 2 mutations » INDIA variants. 7/ Suggesting a possible variants spike mRNA palindrome symmetry metastructure improving mRNA stability then infectiousness. 8/ Analysing Fibonacci Metastructures in the mRNA coding for the vaccines PFIZER and MODERNA. 9/ Does the CG-rich modification of the synonymous codons of the spikes of the 2 mRNA vaccines affect the expression and quantity of SARS-CoV2 antibodies? 10/ The exceptional case of the Brazilian variant P.1. Particularly, we suggest the following conjecture at mRNA folding level : CONJECTURE of SARS-CoV2 VARIANTS: The growth of long Fibonacci structures in the shape of "podiums" for almost all of the variants studied (UK, California, South Africa, India, etc.) suggests the probable folding of the Spike mRNA in the form of a "hairpin", which can strengthen the cohesion and the lifespan of this mRNA. Finally, we show that these kinds of Fibonacci matastructures disapear TOTALLY by analysing the published mRNA sequences of PFIZER and MODERNA vaccines. One fact is certain, the two mRNAs of the Moderna and Pfizer vaccines will result in a low functionality of the spike vaccine. This is because their designers by seeking greater stability, have doped to build CG rich sequences which, as soon as they are inserted into the human host, will, paradoxically, seek to mutate, like SARS-CoV2 variants, towards CG ==> UA forms in order to improve their STABILITY and LIFETIME. We conclude using new biomathematics theoretical methods (Master code and numerical standing waves), and comparing the Spikes of the two vaccines Moderna and Pfizer, that there will be very probable differences in stability and shelf life of the two respective mRNAs vaccines. However, “State of the Art” analyzes will disclose that their two protein sequences are strictly identical. By modified their synonymous codons using different strategies, no one can guarantee that the quantity of antibodies generated will be identical in the two cases. We wish to draw attention to the great ADAPTATION power - at the global scale of their genomes - of the most infectious VARIANTS, such as the BRAZIL 20J / 501Y.V3 variant (P.1). This is very worrying for the VACCINES <==> VARIANTS run: We demonstrate how the Brazilian variant P.1 which becomes uncontrollable in Brazil in April 2021 has a level of organization of long metastructures of 17,711 bases covering the genome which is 3.6 more important than that of the 2 reference genomes SARS-CoV2 and worldwide D614G. We suggest that this high level of overall structure of this variant contributes to the stability of this genome and, might explain its greater contagiousness.

Acellular bacterial ghosts (BGs) are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs) were generated by chemically induced lysis and the method is based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH), acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, < 50.0, 25.0, 6.25, 1.56 and 0.781 mg/ml. Except boric acid, the lysis efficiency was reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs showed completely DNA-free that was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS) extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS), anti-inflammatory cytokine (IL-10) and dual activities (IL-6) in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning electron microscopy showed the formation of trans-membrane lysis tunnel structures in the NaOH-induced VPGs. SDS-PAGE and agarose gel electrophoresis also confirmed that cytoplasmic proteins and genomic DNA released from the VPGs to culture medium through the lysis tunnel structures. Taken together, all these results indicated that the NaOH-induced VPGs show the potency of safe, economical and effective inactivated bacterial vaccine candidate.

SARS-CoV-2 or COVID-19, a new seventh human corona virus, has out-broken in Wuhan, China since 31^st December 2019, and quickly escalated to take the form of pandemic which killed many human beings throughout almost all countries across continents. The rapidity of its transmission from human to human is far greater than all previous human corona viruses which came into existence like SARS-CoV, MERS-CoV, etc. The nucleotide sequence of SARS-CoV-2 (isolates Wuhan-Hu-1) is 29,875 bp in ss-RNA. Symptoms of SARS-CoV-2 infected pneumonia include from asymptomatic to high fever and/or respiratory illnesses. Coronavirus virion (spherical/round /elliptical in shape) consists of three parts- outer membrane or envelope, nucleocapsid and genome (RNA). SARS-CoV-2 was shown to use receptor, angiotensin converting enzyme 2 (ACE2) for attachment to the cells through its surface spike (S) protein (S1), and the virion enters into the host cell through two routes- direct membrane fusion and endocytotic pathway. The RNA of SARS-CoV acts directly as mRNA and here minus(-) 1 programmed ribosomal frameshift (-1PRF) is being operated by slippery sequence and pseudoknot, so it translates 16 nonstructural proteins including RNA dependent RNA replicase. Then genomic RNA replicated continuously on – strand RNA template and subgenomic RNA transcribed discontinuously on –RNA template to sgmRNA. Subgenomic RNAs/sgmRNAs synthesize all structural proteins. This article takes into consideration the details of established theories of viral structure, viral attachment, mode of entry into human cells, different models of replication and transcription of virus genome proposed by eminent scientists over the years, and makes an in depth examination highlighting meaningful points or important target cites of viral propagation or synthesis, which are conserved, for prompt development of potent drugs or vaccine to counter COVID-19 for which human race is anxiously and eagerly waiting.

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.

The SARS-CoV-2 is a recently identified positive sense single stranded RNA virus and member of the coronavirus family of viruses. It is thought to be the etiological factor for the ongoing COVID-19 pandemic. This virus is thought to have originated from bats and acquired ability of human-to-human transmission. While SARS-CoV-2 is relatively benign, it has infected more than half a million people (as of March 29^th 2020) worldwide and the number of infected people continues to rise. More than 170 countries have reported COVID-19 positive cases. With a mortality rate of less than both the previous coronavirus outbreaks, COVID-19 has (conversely) caused the death of over 33,980 (as of 29^th March, 2020 at 22.00 hours EDT) people worldwide and the number is increasing. Given the enormous impact of this virus on human health and wellbeing and consequent devastating impacts on world trade, economics and quality of life, it is important to understand this virus better and get insight into its pathogenic mechanisms which will aid in devising effective measure to curb its spread and predict future pattern of its interaction with humans. Though very little is known about this SARS-CoV-2 but its mechanisms and patterns of spread can be speculated (with caution, nevertheless) from what we know about its closest relatives SARS-CoV-1 (responsible for SARS-2002 epidemic) and MERS-CoV (responsible for MERS-2012 epidemic). In the present review, we aim at bringing together the coherent and peer reviewed literature about the SARS-CoV-2 and its close relatives and try to understand its infection patterns and reconstruct its pathogenic mechanisms with anecdotes on diagnosis and future directions. We hope that this paper will serve the purpose of being a reliable source of information to scientists, clinicians and general public.

The outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes severe respiratory infection (COVID-19) has spread in China, and the world health organization declared it pandemic. However, no approved drug or vaccines are available, and treatment is mainly supportive and through a few repurposed drugs. In this urgency situation, development of SARS-CoV-2 based vaccines is immediately required. Immunoinformatic and molecular modelling are generally used time-efficient methods to accelerate the discovery and design of the candidate peptides for vaccine development. In recent years, the use of multiepitope vaccines is proved to be a promising immunization strategy against viruses and pathogens, which induce more comprehensive protective immunity. The current study demonstrated a comprehensive in-silico strategy to design stable multiepitope vaccine construct (MVC) from B-cell and T-cell epitopes of essential SARS-CoV-2 proteins with the help of adjuvants and linkers. The integrated molecular dynamics simulations analysis revealed the stability of MVC and its interaction with human Toll-like receptors (TLRs), which trigger an innate and adaptive immune response. Later, the in-silico cloning in a known pET28a vector system also estimated the possibility of MVC expression in E. Coli. Despite this study lacks validation of this vaccine construct in terms of its efficacy, the current integrated strategy encompasses the initial multiple epitope vaccine design concepts. After validation, this MVC can present to be a better prophylactic solution against COVID-19.

An experimental study is carried out in a cavitation tunnel on a propeller operating downstream of a non-uniform wake. The goal of this work is to establish quantitative correlations between the near pressure field and the cavitation pattern that takes place on the propeller blades. The pressure field is measured at the walls of the test section and in the near wake of the propeller, and is combined with quantitative high-speed image recording of the cavitation pattern. Through simple harmonic analysis of the pressure data and image processing techniques that allow to retrieve the cavitation extension and volume, we discuss the potential sources that generate the pressure fluctuations. Time correlations are unambiguously established between pressure peak fluctuations and cavitation collapse events, based upon the Rayleigh collapse time. Finally, we design a model to predict the cavitation-induced pressure fluctuations from the derivation of the cavitation volume acceleration. This simple model demonstrates a remarkable agreement with the actual pressure field.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PF4) autoantibodies.

The current report represents a case of a 77-year-old man with Parkinson’s disease who died three weeks after receiving his third COVID-19 vaccination in January 2022. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov- 19 vector vaccine, followed by two more doses with the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to the ambivalent clinical features noted before death. The underlying illness (Parkinson’s disease) was confirmed by autopsy. However, no sign of a florid COVID-19 was discovered. Meanwhile, the immunohistochemical staining of the brain and heart revealed previously undiagnosed conditions. The brain, in distinctive, revealed multifocal necrotizing encephalitis with massive inflammatory lymphocyte infiltrates. In addition, the heart showed signs of serious myocarditis. Finally, immunohistochemical staining revealed that the SARS-CoV-2 spike protein was evident in the tissues investigated. Based on these immunohistochemical findings, it appears that the inflammatory changes in the patient's brain tissues are most likely the result of immunological processes. Concurrently, the absence of SARS-CoV-2 nucleocapsid-protein was evidenced, indicating that the detected spike-protein is unrelated to a SARS-CoV-2 infection. If such an infection was the cause of the spike protein, the SARS-CoV-2 nucleocapsid protein would also be detectable. As a consequence, the confirmed presence of the spike protein had to be attributed to the previous vaccination with the BNT162b2 mRNA vaccine that the deceased patient had received.

An increasing number of aircraft is equipped with wing tip devices, which either are installed by the aircraft manufacturer at the production line or are retrofitted after the delivery of the aircraft to its operator. Installation of wing tip devices has not been a popular choice for regional turboprop aircraft and the novelty of the current study is to investigate the feasibility of retrofitting the British Aerospace (BAe) Jetstream 31 with an appropriate wing tip device (or winglet) to increase its cruise range performance, taking also into account the aerodynamic and structural impact of the implementation. To the best of the knowledge of the authors, no previous study exists which has attempted to assess the winglet retrofit of an existing aircraft type of similar size and operating profile. The optimal winglet design achieved a 2.38% increase of the maximum range by reducing the total drag by 1.19% at a mass penalty of 3.25%, as compared with the baseline aircraft configuration. Other designs were found to be more effective in reducing the total drag, but the structural reinforcement required for their implementation outweighed the achieved performance improvements. Since successful winglet retrofit programs for typical short to medium range narrow body aircraft report even more than 3% of block fuel improvements, undertaking the project of installing an optimal winglet design to the BAe Jetstream 31, should also consider a Direct Operating Cost (DOC) assessment on top of the aerodynamic and structural aspects of the retrofit.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.

Phytophthora. infestans is a well known late blight causing oomycetes pathogen. It evolves and adapts to the host background and new fungicide molecules rapidly within a few years of their release, may be due to the predominance of transposable elements in its genome. Frequent and huge applications of fungicides cause environmental concerns. Here we developed target specific RNA interference based molecules, that are capable of effectively reducing the late blight infection. cDNA microarray expression data was used for the selection of genes involved in the early stage of infection process, sporulation etc. The in vitro synthesis of double stranded RNA molecule, targeting SDH, EF-1α, GPI-HAM344, PLD-3 and HSP-90 encoding genes revealed the reduction in growth, sporulation and symptom expression, which were subsequently assessed by culture bioassay, detached leaf assay and topical application methods. The multiple genes targeted dsRNA nano clay sprayed plants showed enhanced disease resistance (4% disease severity) and least sporulation (<1x103), compared to naked dsRNA spray. Use of nano clay was assumed to be involved in the effective delivery, protection and boosting the action of RNAi in potato plants. A significant difference in the growth, sporulation count, disease severity and reduced expression of the genes and confocal microscopy imaging authenticates the effects of SIGS on late blight disease progression. Our research demonstrated that topical dsRNA nano clay spray under the open-air environment could be an alternative to chemical fungicides and transgenic approaches as a novel plant protection strategy for late blight in an environmentally friendly manner.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. So, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children do not suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats also do not suffer from the virus they transmit, and bats too have a much higher level of melatonin. Viruses generate an explosion of reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. Melatonin inhibits the programmed cell death which coronaviruses induce, causing significant lung damage. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks the inflammasome. The immune response is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the negative effects of coronavirus infection on patients’ health after the active phase of the infection is over.

This is a case study of a 55-year-old patient who died four months after receiving the mRNA-vaccine BNT162b2 (Pfizer-BioNTech) against COVID-19 as a second dose, following an initial vaccination with the ChAdOx1 nCov-19 vector vaccine (AstraZeneca) two months earlier. The autopsy diagnosis revealed general atherosclerosis. The histopathologic analyses of cardiac tissue demonstrated the presence of a thrombus occluding the right coronary artery (RCA) without evidence of plaque rupture. As a substitute trigger of clotting, the RCA presented with characteristics of acute lymphocytic vasculitis that extended to vasa vasorum in the adventitia and vessels in adjacent adipose tissue. Microthrombi were occasionally detected in these small vessels. It was obvious that lymphocytic myocarditis had been a chronic ongoing process temporally distinct from acute myocardial infarction. The myocardium contained patchworks of fibrotic areas alongside foci of displaying acute inflammation and fresh myocyte damage. SARS-CoV-2 Spike protein, but not nucleocapsid protein was sporadically detected in vessel walls by immunohistochemical assay. The cause of death was determined to be acute myocardial infarction and lymphocytic myocarditis. These findings indicate that myocarditis, as well as thrombo-embolic events following injection of spike-inducing gene-based vaccines, are causally associated with a injurious immunological response to the encoded agent. Because of the fact that the immune response to a first gene-based vaccination is very low in comparison with the immune response to the second vaccination, the found adverse events has rather to be attributed to the mRNA-based second vaccination as to the initial vector-based one.

In resettlement planning literature, much has been written on economic, land valuation and compensation, infrastructure and services aspects of the land. Psychological risks and stresses of resettled communities, however, have been under-researched. The current research looks at the psychological risks of resettlers in a Development-Induced Displacement and Resettlement (DIDR) project in Sri Lanka. Focusing on the stages of resettlement planning process discussed by Scudder and Colson four-stage model (1980) and the psychological risks discussed by Cernea’s (1990) impoverishment risks and reconstruction (IRR) model. This study evaluates the significant level of the psychological risks faced by the communities in DIDR projects in Sri Lanka relating to before and after resettlement. Moragahakanda Resettlement Project (MRP) was selected as the case study which is located in Naula DS division of Matale District, Central Province, Sri Lanka. A questionnaire survey, documents and field observations were used to evaluate the current psychological risks. The responses received from multiple choice questions were analyzed by Significant Point (SP) index. The research findings point that there are no conspicuous changes of psychological risks related to before/after resettlement has occurred in re-settlers. The findings highlight that the psychological risk levels in transition stage have remained the same level in the potential development stage. This research provides a systematic guidance enabling the physical planners to prioritize the most significant psychological risks which should be considered in the decision-making process of DIDR projects.

We use earthquake ground motion modelling via Ground Motion Prediction Equations (GMPEs) and numerical simulation of seismic waves to consider the effects of site amplification and basin resonance in Jakarta, the capital city of Indonesia. While spectral accelerations at short periods are sensitive to near-surface conditions (i.e., Vs30), our results suggest that, for basins as deep as Jakarta’s, available GMPEs cannot be relied upon to accurately estimate the effect of basin depth on ground motions at long periods (>1 s). Amplitudes at such long periods are influenced by entrapment of seismic waves in the basin, resulting in longer duration of strong ground motion, and interference between incoming and reflected waves as well as focusing at basin edges may amplify seismic waves. In order to simulate such phenomena in detail, a basin model derived from a previous study is used as a computational domain for deterministic earthquake scenario modeling in a 2-dimensional cross-section. A M_w 9.0 megathrust, a M_w 6.5 crustal thrust and a M_w 7.0 instraslab earthquake are chosen as scenario events that pose credible threats to Jakarta, and the interactions with the basin of seismic waves generated by these events were simulated. The highest PGV amplifications are recorded at sites near the middle of the basin and near its southern edge, with maximum amplifications of PGV in the horizontal component of 200% for the crustal, 600% for the megathrust and 335% for the deep intraslab earthquake scenario, respectively. We find that the levels of ground motion response spectral acceleration fall below those of the 2012 Indonesian building Codes's design response spectrum for short periods (< 1 s), but closely approach or may even exceed these levels for longer periods.

Fast neutron (FN) radiation mediated mutagenesis is a unique approach among the several induced mutagenesis methods being used in plant science in terms of impacted mutations. The FN mutagenesis usually creates deletions from a few bases to several million bases (Mb). A library of random deletion generated using FN mutagenesis lines can provide indispensable resources for the reverse genetic approaches. In this review, information from several efforts made using FN mutagenesis has been compiled to understand the type of induced mutations, frequency, and genetic stability. Concerns regarding the utilization of FN mutagenesis technique for a plant with different level of ploidy and genome complexity are discussed. We have highlighted the utility of next-generation sequencing techniques which can be efficiently utilized for the characterization of mutant lines as well as for the mapping of causal mutations. Pros and cons of Mut-map, MutChromSeq, exon capture, whole genome sequencing, MutRen-Seq, and different tilling approaches can be used for the detection of FN-induced mutation has also been discussed. Genomic resources developed using the FN mutagenesis have been catalogued wooing to meaningful utilization of the available resources. The information provided here will be helpful for the efficient exploration for the crop improvement programs and for better understanding of genetic regulations.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Our first modern global pandemic is caused by a nanosized lipid vesicle, called SARS-CoV-2. Its molecular structure and biogenesis have remarkable similarities with Extracellular Vesicles (EVs, most notably exosomes) that are constantly shed by all cells during their life. Their resemblance may not be a coincidence. Growing body of evidence has shown that EVs have significant roles in various biological processes, including viral infection, transmission and anti-viral response. Drawing comparison with the virus might shed light on how we could fight the COVID-19 disease. This may include novel EV research and diagnostics technologies as well as novel EV-based treatments.

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

During December 2019, a novel coronavirus named as 2019-nCoV, has emerged in Wuhan, China. The human to human transmission of this virus has also been established. Untill now the virus has infected more than seven thousand people and has spread to fifteen countries. The World Health Organization (WHO) has declared 2019-nCoV as global health emergency due to its outburst well beyond China. There is need to develop some vaccines or therapeutics to control or prevent 2019-nCoV infections. The bottleneck with current conventional approaches is that these require longer time for vaccine development. However, computer assisted approaches help us to produce effective vaccine in short time compared with conventional methods. In this study, bioinformatics analysis was used to predict B cell and T cell epitopes of surface glycoprotein of 2019-nCoV that could be suitable to trigger significant immune response. The sequence of surface glycoprotein was collected from the database and analyzed to identify the immunogenic epitope. Both B cell and T cell epitopes were analyzed so the predicted epitopes can stimulate both cellular and humoral immune responses. We predicted 13 B cell and 05 T cell epitopes that later on were joined with GPGPG linker to make a single peptide. This computational approach to design a multi epitope peptide vaccine against emerging 2019-nCoV allows us to find novel immunogenic epitopes against the antigen targets of surface 2019-nCoV surface glycoprotein. This multi epitope peptide vaccine may prove effective to combat 2019-nCoV infections.

This work communicates results from optical emission spectroscopy following laser-induced optical breakdown at or near nanomaterial. Selected atomic lines of silver are evaluated for consistent determination of electron density. Comparisons are presented with Balmer series hydrogen results. Of particular interest are measurements free of self-absorption effects. For several silver lines, asymmetries are observed in the recorded line profiles. Electron densities of interest range from 0.5 to 3 × 10¹⁷ cm^-3, for 5 nanosecond Q-switched Nd:YAG radiation at wavelengths of 1064, 532, and 355 nm, and for selected silver emission lines including 328.0, 338.2, 768.7, and 827.3 nm, and the hydrogen alpha Balmer series line at 656.3 nm. Line asymmetries are presented for the 328.0 nm Ag I line that is measured following generation of the plasma due to multiple photon absorption. This work explores electron density variations for different irradiance levels, and reports spectral line asymmetry of resonance lines for different laser fluence levels.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. 5 to 10% of recovered patients in Wuhan test positive again; this suggest that for controlling COVID-19, vaccines may be better option than drugs. A clinical trial to evaluate an anti-COVID-19 vaccine has started recently. However, its efficacy and potency have to be evaluated and validated. As an alternative, we are presenting a first-of-its-kind, designed multi-peptide subunit based epitope vaccine against COVID-19. The vaccine construct comprise an adjuvant, CTL, HTL, and B-cell epitopes joined by linkers. The vaccine is non-toxic, non-allergenic, thermostable and immunogenic with the capability to elicit a humoral and cell-mediated immune response. The findings are validated with high-end computation-based methods. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as public health priority.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N_CTL=8 and N_HTL=6) and B-cell (N_LBL=4) epitopes from each LASV-derived protein with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor (TLR2) showed binding efficiency followed by dynamic simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

Background: The morbidity of myocardial infarction is keeping raise in this decade. Because of high safety and operability , percutaneous coronary intervention(PCI) has been used to conquer this disease for more than 20 years.An important complication of PCI is contrast induced nephropathy(CIN), which raises our attention. Previously, we started a study to explore the correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention. Our study showed that the rate of CI-AKI in patients with post-procedural myocardial injury and undergoing elective PCI was higher than that in patients free of injury. Methods: In this study,forty male rats were randomly divided into four groups: control group (n=8), CM group (n=12), AMI group (n=8) and AMI+CM group (n=12), then velocity of renal artery blood flow (VRABF), computer tomography (CT), serum creatinine(Scr), reactive oxidative species (ROS), periodic acid-Schiff (PAS) and TUNEL were used to estimate the injury of kidney. We analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. Serum levels of creatinine (SCr) and the eGFR before coronary angiography, and 24–72 h after contrast administration were recorded to assess the renal function. Results: The data showed that VRABF was lower in AMI+CM group than CM group from 0 minute to 24h and CT number in cortex was higher in AMI+CM group than CM group at 4-hour. As well as the level of Scr in AMI+CM group displayed a significantly increase at 24-hour compared with CM group. The histopathologic scores and percentage of tubular cell apoptosis were higher in AMI+CM group at 24-hour. In 327 patients, we found that CI-AKI occurred more often in subjects with post-procedural myonecrosis (PMN) than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Conclusion: Compared to the elective patient, the injury of CIN exhibited a higher severity in AMI patient.

Dengue virus (DENV), the causative agent of dengue fever (DF), is one of the most important mosquito-borne viruses that can infect humans. Although much effort has been made on prevention and control of dengue, there are currently no anti-viral drugs or worldwide approved vaccines yet. In this study, we immunized six-week-old Balb/c mice with DNA vaccine candidates E and NS1-2a of DENV serotype 2 or the combination of them (E+NS1-2a) via an electroporation (EP)-assisted intramuscular gene delivery system and evaluated the immune response and protection. The highest specific antibody titres and cytokine levels secreted by splenocytes as well as the highest survival rate were observed in the E+NS1-2a group, followed by E group and NS1-2a group. Our data suggested that the combination of E and NS1-2a delivered by EP may be a superior preventive strategy against DENV.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.

Global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries with high dengue endemicity (>1.5 million cases/year) are observably less hit by COVID-19 in terms of infection, transmission and mortality. Based on non-overlap of dengue and COVID-19 severity maps and evidence of SARS-CoV-2 serological cross-reactions with dengue, we wonder whether immediate immunization of susceptible populations in Europe, North America and Asia (China, Iran) with available live-attenuated dengue vaccines, will cue the anti-viral immune response to thwart COVID-19 (viral interference). Risk of developing post-vaccination “Antibody-dependent Enhancement” is low as dengue is not endemic in the aforesaid regions.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

A SARS-CoV receptor-binding domain (RBD) recombinant protein was developed and manufactured under current good manufacturing practices in 2016. The protein known as RBD219-N1 when formulated on Alhydrogel®, induced high-level neutralizing antibodies and protective immunity with minimal immunopathology in mice after a homologous virus challenge with SARS-CoV (MA15 strain). In this report, we examined published evidence in support of whether the SARS-CoV RBD219-N1 could be repurposed as a heterologous vaccine against Coronavirus Infectious Disease (COVID)-19. Our findings include evidence that convalescent serum from SARS-CoV patients can neutralize SARS-CoV-2. Additionally, a review of published studies using monoclonal antibodies (mAbs) raised against SARS-CoV RBD and that neutralize the SARS-CoV virus in vitro, finds that some of these mAbs bind to the receptor-binding motif (RBM) within the RBD, while others bind to domains outside this region within RBD. This information is relevant and supports the possibility of developing a heterologous SARS-CoV RBD vaccine against COVID-19, especially due to the finding that the overall high amino acid similarity (82%) between SARS-CoV and SARS-CoV-2 spike and RBD domains is not reflected in RBM region (59%). However, the high similarity (94%) in the region outside of RBM offers the potential of conserved neutralizing epitopes between both viruses.

A metastable β-Ti alloy, Ti–10V–3Fe–3Al (wt.%), was subjected to thermos-mechanical processing including the compression test at 725°C, which is below the β transus temperature (780°C), and at strain rate of 10-3s-1. The presence of phases was determined using transmission electron microscopy and X-ray diffraction. Although the dynamic recovery took place together with slip, both deformation-induced α˝ martensite and ω were detected as other operating mechanisms for the first time in metastable-β Ti alloys deformed in α+β region. The volume fraction of stress-induced α˝ was higher than that of the same alloy deformed at room temperature due to higher strain applied. Stress-induced twinning was not operational, which could be related to the priority of slip mechanism at high temperature resulted from thermally-assisted nucleation and lateral migration of kink-pairs.

With the onset of the COVID19 pandemic, information technology has played a critical role in healthcare. A broad spectrum of information technology tools and applications played an essential role to create awareness of the COVID19 vaccination drive and its health benefits. We use the COVID-19 Global Beliefs, Behaviors, and Norms Survey for analysis of prevalence and factors associated with vaccination drives among men and women aged 20-80 years in 60 countries worldwide. Our analysis of the global survey offers a unique perspective about the role of information technology associated with vaccination drives involving social norms and human behavior among 437,236 respondents. The international survey was organized using a pre-registered randomized experiment demonstrating the role of technology in reaching out to people based in diverse communities and evaluating their beliefs, behavior, and social norms. The study shows that vaccine acceptance can vary due to descriptive norms. Our analysis shows 65.06% of people all over the globe are willing to get vaccinated and a large proportion of the population thinks that the COVID19 pandemic is a viable threat to the community and preventive measures need to be taken including vaccination drives.

A B S T R A C T Genital herpes disease is caused mainly by herpes simplex virus type 2 (HSV-2), which is sexually transmitted with a high prevalence in both developed and developing countries. No vaccine is currently available against genital herpes. In this study, we introduced and expressed two genes encoding HSV-2 glycoprotein D (gD) and VP16 protein and a GFP marker gene (control) in tobacco seedlings. Positive plant infection was assessed through characteristic tobacco mosaic virus disease symptoms on leaves and by monitoring the fluorescence emitted by the expressed GFP protein. Expression of the HSV-gD2 and VP16 antigens was verified by RT-PCR, ELISA and Western blot. As a proof of concept, the immunogenicity and the protection ability of the plant produced gD antigen was tested in a mouse model of genital herpes and compared to gD antigen produced in a mammalian expression system. This showed that the plant-gD preparation, when used in combination with a CpG oligodeoxynucleotide as adjuvant, was highly immunogenic and capable of inducing complete immunity to lethal vaginal HSV-2 challenge in mice. Thus, the data presented here may have implications for the development of a production system for highly immunogenic plant-based HSV-2 vaccine antigens.

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

Our previous in vitro reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of chelesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of chelesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.

Traditional winglets are designed as fixed devices attached at the tips of the wings. The primary purpose of the winglets is to reduce the lift-induced drag, therefore improving aircraft performance and fuel efficiency. However, because winglets are fixed surfaces, they cannot be used to control lift-induced drag reductions or to obtain the largest lift-induced drag reductions at different flight conditions (take-off, climb, cruise, loitering, descent, approach, landing, and so on). In this work, we propose the use of variable cant angle winglets which could potentially allow aircraft to get the best all-around performance (in terms of lift-induced drag reduction), at different flight phases. By using computational fluid dynamics, we study the influence of the winglet cant angle and sweep angle on the performance of a benchmark wing at Mach numbers of 0.3 and 0.8395. The results obtained demonstrate that by adjusting the cant angle, the aerodynamic performance can be improved at different flight conditions.

It is important to distinguish between natural earthquakes and those induced by CO2 injection at carbon capture and storage sites. For example, the 2004 Mw 6.8 Chuetsu earthquake occurred close to the Nagaoka CO2 storage site during gas injection, but we could not quantify whether the earthquake was due to CO2 injection or not. Here we simulated changes of pore pressure during CO2 injection at the Nagaoka site and compared them with estimated natural seasonal fluctuations of pore pressure due to rainfall and snowmelt as well as estimated pore pressure increases related to remote earthquakes. We clearly distinguished changes of pore pressure due to CO2 injection from those due to rainfall and snowmelt. The simulated local increase in pore pressure at seismogenic fault area was much less than the seasonal fluctuations related to precipitation and increases caused by remote earthquakes, and the lateral extent of pore pressure increase was insufficient to influence seismogenic faults. We also demonstrated that pore pressure changes due to distant earthquakes are capable of triggering slip on seismogenic faults. The approach we developed could be used to distinguish natural from injection-induced earthquakes and will be useful for that purpose at other CO2 sequestration sites.

Background: While mankind is still dealing with the COVID-19 pandemic, on May 7, 2022, a case of monkeypox virus (MPXV) has been reported to the WHO. Monkeypox is a viral zoonotic disease with characteristics comparable to those seen in smallpox cases in the past. It has been a public health threat, particularly in Africa, but recently have been circulating the world, consequently, may become a global public health threat in a very short period. Thus, the current work was planned and then constructed a multi-epitope vaccine that can evoke an immunological response against MPXV utilizing cell surface-binding protein as a target in order to develop a novel vaccine that is both safe and almost free of side effects. Results: The proposed vaccine composed of 304 amino acids and was shown to be antigenic in Vaxijen server (0. 5311) and nonallergenic in AllerTop server. The 3D structure of the designed vaccine is predicted, refined and validated by various in silico tools to assess the stability of the vaccine. Moreover, solubility of the vaccine construct was found greater than the average solubility provided by protein-Sol server indicating the solubility of the vaccine construct. Moreover, the most promising epitopes bound to MHC I and MHC II alleles were found having good binding affinities with low energies ranging between ₋7.0 - ₋8.1kcal/mol. Conclusion: We conclude from our research that the cell surface-binding protein is one of the primary proteins involved in MPXV pathogenesis. The most promising epitopes were selected using a rigorous procedure and used for vaccine design. As a result, our study will aid in the development of appropriate therapeutics and prompt the development of future vaccines against MPXV, which could serve as an important milestone in the production of an antiviral vaccine against MPXV.

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, negative regulation of growth, cellular response to Zn2+- Cd2+, Wnt and NIK/NF-kappaB signalling, which refine the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations like α-particles and carbon-ions.

Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide-based, glycoconjugate, protein-based and combined conjugate vaccines) that are approved to target five of the six disease-causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future.

In this paper, we proposed a novel saddle type FinFET (S-FinFET) to effectively solve problems occurring under the capacitor node of dynamic random-access memory (DRAM) cell and showed how its structure was superior to conventional S-FinFETs in terms of short channel effect (SCE), subthreshold slope (SS), and gate-induced drain leakage (GIDL). The proposed FinFET exhibited 4 times lower Ioff than modified S-FinFET called RFinFET with more improved DIBL characteristics while minimizing Ion reduction compared to RFinFET. Our results also confirmed that the proposed device showed improved DIBL and Ioff characteristics as gate channel length decreased.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcome. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is the virus that caused COVID-19 around the world. The disease starts off as a flu-like symptom and then eventually spreads in the human body.Infections are easily transmitted from human to human which makes it more severe among individuals. SARS-CoV-2 virus is in the same family of viruses SARS and MERS.As of today, there is no approved vaccine that can cure COVID-19. However, potential treatments showing promising improvement results among affected COVID-19 patients. In this review, the effectiveness of the current treatments for COVID-19 has been explored.

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

ABSTRACT. In this paper, we run for all INDIA mutations and variants a biomathematical numerical method for analysing mRNA nucleotides sequences based on UA/CG Fibonacci numbers proportions (Perez, 2021). In this study, we limit ourselves to the analysis of whole genomes, all coming from the mutations and variants of SARS-CoV2 sequenced in India in 2020 and 2021. We then demonstrate - both on actual genomes of patients and on variants combining the most frequent mutations to the SARS-CoV2 Wuhan genomes and then to the B.1.617 variant - that the numerical Fibonacci AU / CG metastructures increase considerably in all cases analyzed in ratios of up to 8 times. We can affirm that this property contributes to a greater stability and lifespan of messenger RNAs, therefore, possibly also to a greater INFECTUOSITY of these variant genomes. Out of a total of 108 genomes analyzed: - None ("NONE") of them contained a number of metastructures LOWER than those of the reference SARS-CoV2 Wuhan genome. - Eleven (11) among them contained the same number of metastructures as the reference genome. - 97 of them contained a GREATER number of metastructures than the reference genome, ie 89.81% of cases. The average increase in the number of metastructures for the 97 cases studied is 4.35 times the number of SARS-CoV2 UA/CG 17711 Fibonacci metastructures. Finally, we put a focus on B.1.617.2 crucial exponential growth Indian variant. Then, we demonstrate, by analyzing the main worldwide 19 variants, both at the level of spikes and of whole genomes, how and why these UA / CG metastuctures increase overall in the variants compared to the 2 reference strains SARS-CoV2 Wuhan and D614G.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

This study measures the noise levels in a baseball stadium and analyzes baseball fans’ attitude of effect of recreational noise exposure on their hearing. In the baseball stadium, noise levels were measured in four seating sections using a sound level meter during the games. The LAeq average of the 16 measures produced 91.7 dBA, showing a significantly high noise level in the red and navy sections. As a function of frequency by LZeq analysis, the noise levels were significantly higher in low frequencies than other frequencies. For the survey sample, 688 randomly selected participants completed a 16-question survey on their noise exposure during the game and on the potential risk of hearing loss. Despite the very high noise levels, 70% of the respondents preferred sitting in either the red or the navy section to be closer to the cheerleaders and to obtain a good view. Most respondents reported that they did not consider wearing earplugs, and one-third experienced hearing muffled speech after the game. We conclude that the noise levels in baseball stadiums are high enough to cause hearing damage and/or tinnitus later, but expect these results to improve public education regarding safe noise exposure during popular sports activities.

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.

We have developed an unsteady and non-linear wind synopsis simulator called RIAM-COMPACT (Research Institute for Applied Mechanics, Kyushu University, COMputational Prediction of Airflow over Complex Terrain) in order to simulate the airflow on a microscale, i.e., a few tens of km or less. In RIAM-COMPACT, the large-eddy simulation (LES) has been adopted for turbulence modeling. LES is a technique in which the structures of relatively large eddies are directly simulated and smaller eddies are modeled using a sub-grid scale model. In the present study, we have conducted the numerical wind diagnoses for Taikoyama Wind Farm nacelle separation accident in Japan. The simulation results suggest that all six wind turbines at the Taikoyama Wind Farm are subject to significant influence from separated flow (terrain-induced turbulence) which is generated due to the topographic irregularities in the vicinity of the wind turbines. A proposal has been also made on reconstruction of the wind farm.

This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.

COVID-19 pandemic has caused a large-scale havoc in almost every country across the globe, putting major challenges for the healthcare system in many parts of the world. Several of the laboratories are running in the race with undying efforts for developing potential vaccine, drugs or therapeutics to treat or prevent the infection. However, with the limited time window and high rate of infection, the task is very big for humanity to find a cure. With hundreds of genomic data of SARS-CoV-2 virus isolates from humans are being submitted almost every day, it is coming into knowledge that virus is mutating, slower in countries with sporadic cases, but higher in countries experiencing large outbreak. These types of mutations in virus may bring challenges in vaccine or therapeutic development for use in each and every country, as each hotspot region may have their own pattern of mutations in virus with ongoing outbreak. In our current study, we retrieved non-synonymous mutation data of around 12,225 SARS-CoV-2 virus samples isolated from humans globally, and discovered all mutations that are collectively happening in antibody epitope regions of the virus country-wise. We found a few numbers of epitope regions in SARS-CoV-2 that are highly conserved collectively in all variants and may be used for epitope-based vaccine development for whole world. We also found epitope regions that are conserved collectively in SARS-CoV-2 variants country-wise and can be used for customized epitope-based vaccine development in each different country.

Introduction.Sars-CoV-2 infection poses particular problems in pregnancy, as the infection more frequently causes severe complications than in unaffected pregnant women, or non-pregnant women with SARS-CoV-2 infection. Now that vaccination is available and rapidly getting implemented worldwide, the question arises whether pregnant women should be vaccinated, and if so, whether they should get priority. Methods. Available scientific data and available guidelines about vaccination against SARS-CoV-2 were collected by the Guideline Committee of the International Society of Infectious Diseases in Obstetrics and Gynecology (ISIDOG), and were analyzed, discussed and summarized as guidelines for health care workers caring for pregnant women. Concluding statements were graded according to the Oxford Evidence Based Medicine Grading System. Results. There is evidence to consider pregnancy as a risk factor for serious complications of COVID-19 infection, even in the absence of additional risk factors, such as hypertension, diabetes and obesity which increase these risks even more in pregnancy. Currently available data slightly favor mRNA-based vaccines above vector-based vaccines during pregnancy and breastfeeding, until more safety data become available. Conclusion. ISIDOG advices policy makers and societies to prioritize pregnant women to receive vaccination against SARS-CoV-2, and favor the mRNA vaccines until further safety information becomes available.

The Covid-19 infodemic can be countered by scientific evidences, clear and consistent communication and improved health literacy of both individuals in need of information and those providing it. A rapid online survey was carried out to evaluate vaccine literacy (VL) skills in the general population and perceptions about candidate Covid-19 vaccines, as well as behavior and beliefs about current vaccinations. Observed VL levels were sufficiently high and consistent with previous observations - where comparable self-reported tools were administered face-to-face and paper-and-pencil - the mean functional score being =2.92, while the interactive-critical one was =3.27, on a maximum of 4. Perceptions regarding future Covid-19 vaccines, along with beliefs about vaccination, were mostly positive and significantly associated with functional and interactive-critical VL scales. Despite obvious limitations, the study confirms that rapid surveys via web are a suitable method to evaluate and trail attitudes during infectious disease outbreaks, and to assess health literacy skills about vaccination, which can be useful to adapt medical communication strategies, for a better understanding of the value of immunization.

Electrically conductive polymer composites are in high demand for modern technologies, however, the intrinsic brittleness of conducting conjugated polymers and the moderate electrical conductivity of engineering polymer/carbon composites have highly constrained their applications. In this work, super high electrical conductive polymer composites were produced by a novel hot embossing design. The polydimethylsiloxane (PDMS) composites containing short carbon fiber (SCF) exhibited an electrical percolation threshold at 0.45 wt%, and reached a saturated electrical conductivity of 49 S/m at 8 wt% of SCF. When reduced the sample thickness from 1.0 mm to 0.1 mm by the hot embossing process, a compression-induced percolation threshold occurred at 0.3 wt%, while the electrical conductivity was further enhanced to 378 S/m at 8 wt% SCF. Furthermore, the additional of a second nanofiller of 1 wt%, such as carbon nanotube or conducting carbon black further increased the electrical conductivity of the PDMS/SCF (8 wt%) composites to 909 S/m and 657 S/m, respectively. The synergy of the densified conducting filler network by the mechanical compression and the hierarchical micro-/nanoscale filler approach has realize super high electrical conductive yet mechanical flexible polymer composites for modern flexible electronics applications.

Background and objectives: Contrast-induced nephropathy (CIN), is an acute renal damage due to contrast agents. This study is conducted to determine the potential diagnostic value of hypoxia-inducible factor 2-alpha (HIF2-α) and to evaluate the renal protective effects of N-acetyl cysteine (NAC) and sildenafil in a rat CIN model. Material/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Totally, rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN+NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modelling, prophylactic treatment was performed at 24th and 48th hours. After 48 hours of the modelling; blood, urine, tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum and urine samples. Renal sections were performed in order for histopathologic and immunohistochemical evaluations. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC, efficiently decreased the renal damage due to contrast agents (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study constructs an experimental base for the use of HIF-2α for clinical prevention and treatment of CIN. Several mechanisms may be postulated for the changes in HIF-2α levels. Besides, the increased HIF-2α levels with CIN and decreased HIF-2α levels after treatment may be used for the treatment and follow-up of patients with CIN.

Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which causes considerable economic losses to the poultry industry worldwide. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing S1 and N proteins, mono-expressing S1 or N proteins alone of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, boosting with the same dose 14 days later, and following challenge with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels as well as the percentages of CD4+ and CD8+ T lymphocytes were detected within 28 days post-vaccination (dpv). The morbidity, mortality, and re-isolation of virus from the tracheas and kidneys of challenged birds were evaluated at 5 days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocyte in rHBM-S1-N group were higher than those of rHBM-S1 and rHBM-N groups, especially the cellular immunity response. At 5 dpc, the mortality, morbidity and virus re-isolation rate of rHBM-S1-N were slightly higher than those of H120 group, but were lower than those of rHBM-S1 group and rHBM-N group. The present study demonstrated that the protection of recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing S1 or N protein alone. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

Purpose: This review features a generalized overview of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The increasing number of reported cases indicated the worldwide distribution of the mosquito vectors, which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. However, the 4 different viral serotypes increases the risk of a life-threatening secondary infection due to the varying serotypes. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

This work examines atomic and molecular signatures in laser-induced plasma in standard ambient temperature and pressure environments, including background contributions to the spectra that depend on the laser pulse-width. Investigations include solids, gases, and nano-particles. Abel inversions of measured line-of-sight data reveal insight into the radial plasma distribution. For nominal 6 nanosecond laser pulses and for pulse-energies in the range of 100 to 800 milli-Joules, expansion dynamics and turbulence due to shock phenomena are elucidated to address local equilibrium details that are frequently assumed in spatially averaged emission spectroscopy. Chemical equilibrium computations reveal temperature dependence of selected plasma species. Specific interests include atomic hydrogen (H) and cyanide (CN). The atomic H spectra, collected following optical breakdown in ultra-high-pure hydrogen and 9:1 mixtures of ultra-pure hydrogen and nitrogen gases, indicate spherical shell structures and isentropic expansion of the plasma kernel over and above the usual shockwave. The recombination radiation of CN emanates within the first 100 nanoseconds for laser-induced breakdown in a 1:1 CO₂:N₂ gas mixture when using nanosecond laser pulses to create the micro-plasma. The micro-plasma is generated using 1064 nm, 150 mJ, 6 ns Q-switched Nd:YAG laser radiation. Measurements of the optical emission spectra utilize a 0.64 m Czerny-Turner type spectrometer and an intensified charge-coupled device.

The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

In this work, the parameters of plasma (electron temperature (T_e), electron density n_e, plasma frequency (f_p) , Debye length (λ_D) and Debye number (N_D)) have been studied by using the spectrometer that collect the spectrum of Laser produce Cadmium telluride plasma at different energies. The results of electron temperature for CdTe range 0.93-1.18 eV also the electron density 5 × 10¹⁰ – 3.8 × 10¹¹ cm^-3 have been measured under vacuum reaching 2.5 × 10^-2 mbar .Optical properties of CdTe were determined through the optical transmission method using ultraviolet visible spectrophotometer within the range 190 – 1100 nm.

This work communicates a review on Balmer series hydrogen beta line measurements and applications for analysis of white dwarf stars. Laser-induced plasma investigations explore electron density and temperature ranges comparable to white dwarf star signatures such as Sirius B, the companion to the brightest star observable from the earth. Spectral line shape characteristics of the hydrogen beta line include width, peak separation, and central dip-shift, thereby providing three indicators for electron density measurements. The hydrogen alpha line shows two primary line-profile parameters for electron density determination, namely, width and shift. Both Boltzmann plot and line-to-continuum ratios yield temperature. The line-shifts recorded with temporally- and spatially- resolved optical emission spectroscopy of hydrogen plasma in laboratory settings can be larger than gravitational redshifts that occur in absorption spectra from radiating white dwarfs. Published astrophysical spectra display significantly diminished Stark or pressure broadening contributions to red-shifted atomic lines. Gravitational redshifts allow one to assess the ratio of mass and radius of these stars, and subsequently, the mass from cooling models.

The human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently chondrogenesis using human pluripotent stem cells are accomplished using human recombinant growth factors. Here, we differentiated human induced pluripotent stem cells (hiPSCs) into chondrocytes and cartilage pellet using minicircle vectors. Minicircles are used as a non-viral gene delivery system for gene therapy in various diseases. Non-viral gene delivery can produce growth factors without integrating into the host genome. Minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor, beta 3 (TGFβ3) were successfully generated and delivered to hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into chondrogenic lineage. Chondrogenic pellets transfected with growth factor-encoding minicircles effectively recovered osteochondral defect in rat models. Taken together, this work shows the potential application of minicircles in cartilage regeneration using hiPSCs.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The present standard-of-care for type 1 diabetes is exogenic insulin substitutional therapy. The most advanced stretegies in this area is the development of hybrid-closed loop system and the producing of long-acting insulins. Progresses in stem cell therapies have started to revolutionize the care of patients with type 1 diabetes; however, significant challenges remain including the limited islets availability, difficulties in maintaining the viability, the heterogeneity within a complex pathology and in patients’ responses to treatment. On the way, a considerable amount of efforts in maximizing the islet transplantation effectiveness by controlling the advantageous of different stem cell approaches. With the availability and the use of big data, the concept of precision medicine is gaining wide attention worldwide and could bring the dream of “presonlaized” therapies as a reality in the near future. Here we review the current range of treatments available as well as recent pre-clinical breakthroughs in the field of personlaized medicine for type 1 diabetes.

Pre-existing fracture and secondary cracks in rock mass are formed by natural power, such as magma condensed to igneous rocks and tectonic movement. The orientation and inclination of these fractures obey certain laws relating to the stress, temperature, minerals, water and so on. Therefore, cracks react differently under the same external loading on the condition of various inclination, fissure apertures, stiffness and joint roughness. To simulate the crack propagation, experiments on hollow cylinder cut by one oblique interface mimicking single fracture accumulated numerous data discovering the failure criterion in accordance with the Mohr-Coulomb criterion. And theory on the Terzaghi’s effective principle take an essential role in controlling the behavior of triggering fault. This paper introduced a series of oblique plane cutting the cylinder regarded as fractures at different inclination to concentrate on how the fracture characteristics effect the stress and strain distribution inside the specimen, especially, the relationship between displacement and water head. The key point of this numerical simulation is coupling the solid phase and the fluid phase, specifically, the mechanic and seepage field. According to the statics, curves referring to deformation and water head could be described as increasing lines. Besides, simulation on coupling solid phase and fluid phase can supply crucial evaluation on activating existing fault, and thus predicting induced seismicity in reservoirs or estimating damage in shale gas exploration.

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

Tilapia lake virus (TiLV) is the main tilapia-infecting virus worldwide, causing serious economic losses. However, there is no vaccine for this viral disease. Here, TiLV ORF10 (TiLV-ORF10) encoding a protein with abundant epitopes was constructed into the eukaryotic expression vector pcDNA3.1, and used to evaluate the immune protective effects in Nile tilapia (Oreochromis niloticus). RT-PCR and western blot analyses confirmed vaccine plasmid expression in tilapia muscle tissues. Moreover, the transcription levels of immunoglobulin M, toll-like receptor 2, myeloid differentiation factor 88, interleukin 8, tumor necrosis factor alpha, gamma-IFN, and nuclear factor κB immune-related genes were statistically significantly upregulated in the spleen, liver, and kidney of vaccinated tilapias (P < 0.05). TiLV challenge experiments showed that relative percent survival (RPS) was significantly enhanced in fish by this DNA vaccine. Moreover, RPS was enhanced further when using a higher amount of the DNA vaccine (85.72% RPS at a DNA dose of 45 μg pcDNA3.1–ORF10). Vaccination with pcDNA3.1–ORF10 significantly reduced virus replication, as evidenced by the low amount of virus in the spleen, liver, and kidney of vaccinated tilapias after TiLV challenge. Thus, pcDNA3.1–ORF10 could induce protective immunity in tilapia and may be a potential vaccine candidate for controlling diseases caused by TiLV.

The color changes corresponding to chromophore structures in lignin caused by exposure of Eucalyptus（Eucalyptus grandis and E. urophylla）to heat were investigated. Eucalyptus wood samples were heated in saturated steam atmospheres for 10 h at 110℃, 130℃, and 150℃. The lignin was isolated before and after heat treatment. The physicochemical properties of the lignin and changes in chromophore structures during heat treatment was evaluated through wet chemical analysis, FTIR, UV-Vis, GPC, XPSand 13C-NMR. The color of the wood became darker and redder with the increase in pressure and temperature. Depolymerization and dehydration reactions occurred via demethoxylation with heat treatment in saturated steam at 110℃ or 130℃. Lignin condensed to form insoluble compounds after heat treatment in saturated steam at 150℃. G units increased and S units decreased through demethylation during heat treatment, as revealed by FTIR and 13C-NMR analysis.

There exists a compelling need to better understand the temporal dynamics of public sentiment towards COVID-19 vaccines in the US on a national and state-wise level for facilitating appropriate public policy applications. Our analysis of social media data from early February of 2021 and late March of 2021 shows that in spite of overall strength of positive sentiment, and increasing numbers of Americans being fully vaccinated, negative sentiment about COVID-19 vaccines still persists among sections of people who are hesitant towards the vaccine. In this study, we performed sentiment analytics on vaccine tweets, studied changes in public sentiment over time, conducted vaccination sentiment validation using actual vaccination data from the US CDC and Household Pulse Survey (HPS), explored influence of maturity of Twitter user-accounts and generated geographic mapping of sentiments by location of Twitter users. Furthermore, we leverage the emotion polarity based Public Sentiment Scenarios (PSS) framework which was developed for COVID-19 sentiment analytics, to systematically analyze directions for public policy processes to potentially improve the administration of vaccines. Application of the PSS framework provides important time sensitive insights for state and federal government agencies and associated organizations to better implement public policy processes for healthcare management, communication, transparency, motivation and societal operational policies such as social distancing. These insights are expected to contribute to processes that can expedite the vaccination program and move closer to the cherished herd immunity goal.

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of EdU⁺/αMHC-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP^high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP^low cells; however, S-phase synchronization didn’t enhance the polycistronic-MGT reprogramming, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

Declaration of smallpox eradication by the WHO on 1980 led to discontinuation of the world-wide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV) and the recent synthetic achievements, increases the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign as no other protective measure has been approved to achieve eradication and ensure world-wide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure, confers effective protection. The long incubation period and the uncertainty of the exposure status in the surrounding population calls for the development and evaluation of safe and effective methods that would allow to extend the therapeutic window and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements and open questions.

The resonance spectra of neutral silver indicate self-absorption for the studied Ag I lines at the wavelengths of 327.9 nm and 338.2 nm. The center dip is associated with self-reversal due to self-absorption in the plasma. The Q-switched radiation of 355 nm, 532 nm, or 1064 nm from a Nd:YAG laser device generates the plasma at the surface of silver nano-material targets, with experiments conducted in standard ambient temperature and pressure laboratory air. Procedures for recovery of the spectral line shapes confirm that over and above the effects of self-reversal, line shape distortion are important in the analysis. The work discusses parameters describing self-absorption when using fluence levels of 2 to 33 J/cm² to generate the plasma. Furthermore, subsidiary calibration efforts that utilize the hydrogen alpha line of the Balmer series show that the Ag I lines at 827.35 nm and 768.7 nm are optically thin.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Globally 30% of landslides occur in the northeastern part of India [1]. One of the major earthquake events in Sikkim, India occurred on 18th September 2011 (Mw 6.9) led to over 300 landslides and 122 human deaths [2]. These landslides not only controlled by natural disasters but initiated due to human activities. The present study considered Lungchok landslide occurred in south district of Sikkim due to 2011 seismic event. The study focused on the failure mechanism of the landslide based on finite element analysis by adopting eight different cases. The deformation characteristic was investigated for dry and saturated slope conditions under static and dynamic behavior considering vehicle loads using GeoStudio software. The FEM analysis has been carried out using load deformation and linear elastic. The analysis shows that the failure of the slope was not sudden due to the 2011 earthquake event, but progressive failure was observed with time and construction activity. The paper demonstrates that, an increase in infrastructure development including construction by hill cutting increased the initiation of landslide with soil erosion. The cracks developed after 2011 earthquake event led to further deformations during future disasters required effective stabilization measures.

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Or-thopoxvirus genu. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods & Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses: ACAM2000, JYNNEOS, and LC16, with the first being a replicating vaccine and the latter being non or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental im-munity to MPV. ACAM2000(a live‐attenuated replicating vaccine) and JYNNEOS (a live‐attenuated, non-replicating vaccine) are two US FDA‐approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer com-plications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or mRNA before monkeypox is declared a pandemic.

Amorphous silicon (α-Si) film present an inexpensive and promising material for optoelectronic and nanophotonic applications. Its basic optical and optoelectronic properties are known to be improved via phase transition from amorphous to polycrystalline phase. Infrared femtosecond laser radiation can be considered as a promising nondestructive and facile way to drive uniform in-depth and lateral crystallization of α-Si films that are typically opaque in UV-visible spectral range. However, so far only a few studies reported on utilization of near-IR radiation for laser-induced crystallization of α-Si providing no information regarding optical properties of the resultant polycrystalline Si films. The present work demonstrates efficient and gentle single-pass crystallization of α-Si films induced by their direct irradiation with near-IR femtosecond laser pulses coming at sub-MHz repetition rate. Comprehensive analysis of morphology and composition of laser-annealed films by atomic-force microscopy, optical, micro-Raman and energy-dispersive X-ray spectroscopy, as well as numerical modeling of optical spectra, confirmed efficient crystallization of α-Si and high-quality of the obtained films. Moreover, we highlight localized laser-driven crystallization of α-Si as a promising way for optical information encryption, anti-counterfeiting and fabrication of micro-optical elements.