Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective anti-viral therapy or vaccine currently exist, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that included in vitro and in vivo models for testing of anti-viral therapies, and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on anti-viral and adjunctive therapies currently being tested or require testing in animal models and randomized clinical trials.

The spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 150 countries in a matter of months. Even though containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, as the US, Spain and Italy have come off worse-off by the spread of the virus, and there is serious concern regarding the national health systems' capacity around the world and Africa, in particular, to effectively respond to the needs of infected patients who require intensive care for the COVID-19 illness. As a result, authorities around the world have resorted to the lockdown strategy to curb the spread of the virus. Therefore, the study aimed at investigating the effect of the lockdown strategy in curbing the spread of the COVID-19 virus in Nigeria. Consequently, the study found daily relative risk increase in cases, and daily relative risk increase in mortality. Also observed is the growth in cases in areas where active measures were not taken. Further, halt in business activities has rendered many penniless and unable to provide for themselves basic amenities. The study recommends that there is need to implement community-level measures of social distancing which may include closing schools, need for individuals with COVID-19 case or respiratory symptoms be properly taken care of, trace and quarantine those who must have come in contact with affected persons and introducing stay at home palliatives for the general public.

IntroductionThe aim of this study is to describe the epidemiology of all COVID-19 patients in Vietnam and to describe the measures of disease control and prevention implemented. MethodsData were recovered from Wikipedia regarding the 2020 coronavirus pandemic in Vietnam. The period covered was from 23 January to 20 April 2020. Descriptive analysis was stratified by gender, age, country of origin, travel history, clinical symptoms and outcome. A survey of disease control and prevention measures was conducted at the Centre for Disease Control in the Thai Binh province, which is responsible for screening and isolating individuals at high risk of COVID-19. ResultsAs of 20 April 2020, Vietnam had recorded 268 confirmed COVID-19 patients. 55.2% were female. 67.9% were aged 20-49 years and 82.5% were Vietnamese. 60.4% of cases were imported from outside Vietnam. Other cases were acquired in Vietnam by individuals in close contact with imported cases. Only one patient who had not travelled had had no known contact with a confirmed case. 63.1% of patients were asymptomatic. 75.7% of patients were discharged. No deaths were recorded. The Thai Binh CDC surveyed a total of 2,203 persons at risk of COVID-19. 336 persons (15.2%) were isolated at hospitals and 1,411 (64.0%) in dedicated isolation facilities. 16.4% reported at least one respiratory symptom. No positive cases confirmed by RT-PCR have been reported in the Thai Binh province to date. ConclusionThe effect of the systematic screening and isolation strategy made it possible to limit local transmission in Vietnam. Vietnam needs to reinforce diagnostic capacities, prevention measures and provide the necessary epidemiological data on which to base interventions. The wider use of rapid serological tests is also advisable in order to be able to conduct extensive screening in the community.

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This ‘cytokine storm ‘produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1 and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.

The outbreak of coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions and has affected more than 100 countries in recent weeks. It is imperative that global healthcare systems are prepared. Containment initiatives in Jordan, on the other hand, have decreased new cases by over 63%. The Jordanian national health system has been very pleased with its ability to adequately meet the needs of the patients diagnosed with SARS-CoV-2 pneumonia, and includes intensive care. From 2 March to 14 April 2020, between 4% and 8% of active infected patients in Jordan registered daily in intensive care. The percentage is very low.

SARS-CoV-2 is a novel and highly pathogenic coronavirus, which was first diagnosed in Wuhan city, China, in 2019, and spread to 185 countries and territories, and as of April 29, 2020, more than 3.11 million cases were recorded, and more than 217,000 people were killed. Despite all worldwide efforts, there is currently no vaccine, any drugs available to protect people against deadly SARS-CoV-2 coronavirus. The world urgently needs a SARS-CoV-2 coronavirus vaccine or effective antiviral drugs to relieve the human suffering associated with the pandemic that kills thousands of people every day. The SARS-CoV-2 genome encode a non-structural proteins named as ORF1a/b, and structural proteins such as spike (S) glycoprotein, nucleocapsid protein (N), small envelop protein (E) and matrix protein (M). A number of studies have been shown that CoV spike (S) glycoprotein and nucleocapsid protein (N) could be promising targets for vaccine, antibodies and therapeutic drug development to combat with deadly, pandemic SARS-CoV-2. Purposes of the present paper is the sequence analysis and amino acid variations of structural proteins deduced from novel coronavirus SARS-CoV-2 strains, isolated in different countries. Multiple sequence alignment of S, N and E proteins from four different coronavirus species, are also described. It is expected that the data from these studies will be very useful for the the designing and development of vaccines, antibodies and therapeutic agents that can be used to combat with the highly pathogenic SARS-CoV-2 coronavirus worldwide.

There were warnings before; nevertheless the current CoVID-19 pandemic took the world by surprise: within just four month, it conquered the globe and claimed over 200'000 lives. Unprecedented governmental actions put about half of the population under curfew or lock-down. The resulting economic meltdown is expected to eliminate globally 9’000’000’000’000 (9 trillion) USD in 2020 and 2021 alone, a value roughly the size of the yearly GDP of the world’s 150 smallest economies. The resulting crises might cause mass-unemployment and a hunger pandemic later this year. This Essay analyses current statistical data of the CoVID-19 pandemic to develop a guideline for a path through the crisis, minimizing both loss of lives and economic costs. Part 1 details the current situation; part 2 develops a small set of measures, allowing a near normal life until a future vaccination campaign has reached sufficient numbers of people; and part 3 provides some important lessons for the future beyond SARS-CoV-2. The Essay leads to the following key-messages: 1) The CoVID-19 pandemic will stay for at least two more years. This is the minimum time required for a vaccination campaign to reach sufficient numbers of people. 2) The crucial element to control the pandemic is keeping case numbers under the threshold required for a functional tracing, testing & isolation (TTI) strategy. That threshold differs from country to country and strongly depends on culture and the applied tracing technology as well as available testing capacities. 3) The economic burden of a TTI strategy is moderate while fatalities are also reduced. Hence, such an approach is strongly recommended. Its implementation requires a set of simple and cost-effective measures (see figure below), which in combination seem to be sufficient to keep CoVID-2’s reproductive rate at or below 1. 4) Implementing international coordination of actions will be necessary for effective infection-chain tracing5) If case numbers are above the TTI threshold, shutdown measures remain the only option until tracing of infection chains becomes feasible again.6) In the future, neglected pandemic-related research requires a funding boost. Just 1% of the bill of the current crisis could support the research of 45’000 scientist for 20 years.

We describe a 90-year-old male presenting with disequilibrium, loss of balance and difficulty walking for three days prior to initial presentation. Interestingly, he denied cough, fever or dyspnea prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation, diagnosed with COVID-19 infection and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure from SARS-CoV-2 virus. These atypical findings such as presyncope may precede common respiratory complications of SARS-CoV-2.

This document outlines best practice recommendations for an acute care physiotherapy for patients with COVID-19, with an emphasis on critical care rehabilitation including the patients in extra corporeal membrane Oxygenation (ECMO) support, developed for practice in Qatar but adaptable within any settings. This recommendation is the result of a combination of systematic evidence search, subsequent critical evaluation of retrieved evidence and consensus process. The agreed recommendations were integrated into a physiotherapy clinical reasoning algorithm. It includes recommendations on physiotherapy referral, screening, management categories and best practice recommendations. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with suspected and/or confirmed COVID-19.

An outbreak of a pandemic COVID-19 disease caused by a novel coronavirus SARS-CoV-2 has posed a serious threat to human health and the economy of the whole world. Bangladesh is one of the most densely populated countries in the world, which has also come under the attack of this viral disease. This perspective report aimed to describe the responses of Bangladesh to tackle the COVID-19, particularly on how Bangladesh is dealing with this novel viral disease with limited resources. The first case of a COVID-19 patient was detected in Bangladesh on March 8, 2020. Since then, a total of 2,144 peoples are officially reported as COVID-19 infected with 84 deaths. To combat the COVID-19, the government has taken various steps to tackle the epidemic outbreak of it such as diagnosis of the suspected cases, quarantine of doubted people and isolation of infected patients, local or regional lockdown, grant general leave from all offices for staying home of people, increase public awareness and enforce social distancing and so on. In addition, to address the socio-economic situations, the government announced several financial stimulus packages of about USD 11.17 billion. However, very limited diagnostic facilities, health workers, resources such as hospital beds, personal protective equipment, intensive care unit, and ventilators in the hospitals along with limited public unawareness are the major challenges for Bangladesh to tackle the situation effectively. This report described the responses of Bangladesh to tackle the COVID-19 and discusses prevailing challenges to mitigate this highly contagious disease with limited resources.

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

A big race for the search for novel lead has begun due to the emergence of COVID-19 across the globe. More than 6,00,000 cases of afflicted patients worldwide has been reported till date with high mortality and morbidity. At present no approved drugs are known for COVID-19. Phylogenetic analysis present strong nucleotide sequence similarity of around 80% with SARS-CoV. Therefore, the drugs used for treating SARS-CoV and MERS are being used for SARS-CoV-2 also. Recently, the crystal structure of COVID-19 is reported and hence, we have used this tom predict the binding affinity with SARS-CoV-2-main protease and prepared a pharmacophore that may be used for future design of novel inhibitors.

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.

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

Spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) made a historic transition between December 2019 to March 2020. In the present scenario SARS-CoV-2 as becomes a major burden on public health and economic stability of societies around the globe. From the substantial evidences gained from the pandemic of SARS-CoV-2 and MERS-CoV (Middle East respiratory syndrome coronavirus), scientists and clinicians strongly believes that these pathogenic viruses share common homology of some biologically active enzymes which includes RNA-dependent RNA polymerase (RdRP), 3-chymotrypsin-like protease (3CL^pro), papain-like protease (PL^pro) etc. RdRP relatively grabs higher level of clinical importance in comparison with other enzyme target. Indian system of traditional medicine pioneering the therapy towards infectious disease since several centuries. In view of this potential therapeutic leads from some of the Indian medicines along with standard drug favipiravir subjected to docking investigation targeting SARS-CoV-2- RNA dependent RNA polymerase (RdRp). Residual proximity analysis reveals 18 out of 28 compounds reveals potential binding affinity of about 100% with the target amino acid residue (618 ASP, 760 ASP,761 ASP), 7 out of 28 reveals 75% binding efficacy and 3 out of 28 reveals 25% binding efficacy with that of the target residue. Hence further clinical validation may be warranted with proper in-vitro and in-vivo studies prior to the clinical recommendation in treating COVID-19 patient’s.

The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its spread to the whole world is currently posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARS-CoV based on the genome sequence comparison. Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. We analyzed the receptor binding domain (RBD) from recently published 3D structure of spike glycoprotein of SARS-CoV-2 and compared with RBD of SARS-CoV. The observations highlight few important features of RBD in the light of the recently published findings from the 3D structures of spike glycoprotein and its complex with human angiotensin-converting enzyme 2 (ACE2) (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)).

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein is particularly interesting, since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD have important functional roles in viral adhesion and entry.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

Pneumonia caused by a new coronavirus SARS-CoV-2 has caused serious harm to people's lives and health in Wuhan, China. By February 26, 2020, over 80,000 people were infected and 2,814 died from the infection. The initial route of infection is the binding of the spike protein (S protein) of the virus to the angiotensin-converting enzyme 2 (ACE2). From bioinformatics analysis, we found that the S protein of SARS-CoV-2 produced an evolutionary mutation of K403R compared with the S protein of SARS-CoV, forming an adjacent RGD motif at the interaction surface. As the RGD motif is considered as a ligand for many cell surface integrins, we proposed that the binding of S protein of SARS-CoV-2 with integrins may facilitate the infection process of the virus. Therefore, high-throughput virtual screening was performed by choosing the key residues of S protein interface of SARS-CoV-2 and the adjacent RGD motif as potential binding site, to search for the potential agents targeting interaction of S protein of SARS-CoV-2 with both ACE2 and integrins as potential therapeutic drugs. Various libraries including the FDA-approved drugs etc. were screened, and Nadide, Losartan, 9'''-Methyllithospermate B and Leonurine etc. were identified as representative potential drugs candidate for COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a new viral respiratory disease and whether pregnant women are at increased risk of infection is unknown. Viral pneumonia is an important indirect cause of maternal death. Little is known about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Objective: To describe the clinical characteristics of COVID-19 in pregnancy and their newborn infant, and we sought to explored whether the SARS-CoV-2 can be intrauterine vertically transmitted. Study Design: The study was a case series study conducted in the obstetric ward of Tongji Hospital affiliated to Huazhong University of science and technology, Wuhan, China. Demographic, clinical, laboratory and radiological profiles of the SARS-CoV-2 infection case series. A systematic testing procedure for SARS-CoV-2 infection using oropharyngeal swab, placenta tissue, vaginal mucus, and breast milk of mothers. and oropharyngeal swab, umbilical cord blood, and serum of newborns was conducted. Results: We have conducted the most thorough virological assessment to date, and we include a longer clinical observation in mother-infant dyads during hospitalization. The clinical course and outcomes of three pregnant women who acquired SARS-CoV-2 infection late pregnancy are described in mother-infant dyads. Two had caesarean delivery in their third trimester. All patients showed an uneventful perinatal course, and a successful outcome. No infants became infected by vertical transmission or during delivery. Conclusion: No evidence to suggest the potential risk of intrauterine vertical transmission in the case series and further in-depth study is needed. Both the pregnancy woman and infant showed fewer adverse maternal and neonatal outcomes.

Proper satellite-based crop monitoring applications at the farm-level often require near-daily imagery at medium to high spatial resolution. The synthesizing of ongoing satellite missions by ESA (Sentinel 2) and NASA (Landsat7/8) provides this unprecedented opportunity at a global scale; nonetheless, this is rarely implemented because these procedures are data demanding and computationally intensive. This study developed a complete stream processing in the Google Earth Engine cloud platform to generate harmonized surface reflectance images of Landsat7,8 and Sentinel 2 missions. The harmonized images were generated for two agriculture schemes in Bekaa (Lebanon) and Ninh Thuan (Vietnam) during the period 2018-2019. We evaluated the performance of several pre-processing steps needed for the harmonization including image co-registration, brdf correction, topographic correction, and band adjustment. This study found that the miss-registration between Landsat 8 and Sentinel 2 images, varied from 10 meters in Ninh Thuan, Vietnam to 32 meters in Bekaa, Lebanon, and if not treated, posed a great impact on the quality of the harmonized dataset. Analysis of a pair overlapped L8-S2 images over the Bekaa region showed that after the harmonization, all band-to-band spatial correlations were greatly improved from (0.57, 0.64, 0.67, 0.75, 0.76, 0.75, 0.79) to (0.87, 0.91, 0.92, 0.94, 0.97, 0.97, 0.96) in bands (blue, green, red, nir,swir1,swir2, ndvi) respectively. We demonstrated that dense observation of the harmonized dataset can be very helpful for characterizing cropland in highly dynamic areas. We detected unimodal, bimodal and trimodal shapes in the temporal NDVI patterns (likely cycles of paddy rice) in Ninh Thuan province only during the year 2018. We fitted the temporal signatures of the NDVI time series using harmonic (Fourier) analysis. Derived phase (angle from the starting point to the cycle's peak) and amplitude (the cycle's height) were combined with max-NDVI to generate an R-G-B image. This image highlighted croplands as colored pixels (high phase and amplitude) and other types of land as grey/dark pixels (low phase/amplitude). Generated harmonized datasets that contain surface reflectance images (bands blue, green, red, nir, swir1, swir2, and ndvi at 30 meters) over the two studied sites are provided for public usage and testing.

Background and Objectives: Ischemic and idiopathic heart failure are two different etiologies, however reactive cardiac fibrosis together with impaired vasculogenesis has been described in both of them. Implication of main proangiogenic factors as: angiogenin, agiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) has been described mainly in experimental models of heart failure. However, differences in molecular pathways between these cardiomyopathies are still under investigation. In this short communication we aimed to evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic and idiopathic etiology. Methods and Results: Heart tissue from left ventricular walls was obtained at transplantation from ischemic heart disease (IHD), idiopathic cardiomyopathy (ICM) patients. Tissue samples were examined using immunohistochemistry for angiogenic molecules. Immunopositivity (I-pos) for angiopoietin-1 was mainly observed in the cardiomyocytes, while I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Procollagen-I (PICP), angiogenin, Ang-1, Tie-2 receptor, were similarly expressed in IHD and ICM patients. In contrast, endothelial immunopositivity for Ang-2 was higher in IHD samples compared to ICM (p=0.03). Conclusions: Ang-2 expression is different in heart tissue of ICM and ICM patients and distribution of Ang-1 and angiogenin is higher in cardiomyocytes, whereas Ang-2 higher in endothelial cells, suggesting a different pattern of angiogenic stimulation, or at least of altered endothelial integrity. This data may serve for further studies investigating angiogenesis signaling pathways and in HF of different etiology.

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally-induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.

The Sentinel-2 satellite mission offers high resolution multispectral time series image data, enabling the production of detailed land cover maps globally. At this scale, the trade-off between processing time and result quality is a central design decision. Currently, this machine learning task is usually performed using pixelwise classification methods. The radical shift of the computer vision field away from hand engineered image features and towards more automation by representation learning comes with many promises, including higher quality results and less engineering effort. In this paper we assess fully convolutional neural networks architectures as replacements for a Random Forest classifier in an operational context for the production of high resolution land cover maps with Sentinel-2 time series at the country scale. Our contributions include a framework for working with Sentinel-2 L2A time series image data, an adaptation of the U-Net model for dealing with sparse annotation data while maintaining high resolution output, and an analysis of those results in the context of operational production of land cover maps.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

A balanced chromosomal translocation disrupting DISC1 (Disrupted in Schizophrenia 1) gene has been linked to psychiatric diseases, such as major depression, bipolar disorder and schizophrenia. Since the discovery of this translocation, many studies have focused on understating the role of the truncated isoform of DISC1, hypothesizing that the gain of function of this protein could be behind the neurobiology of mental conditions, but not so many studies have focused in the mechanisms impaired due to its loss of function. For that reason, we perform an analysis on the cellular proteome of primary neurons in which DISC1 was knocked down with the goal of identifying relevant pathways directly affected by DISC1 loss of function. Using an unbiased proteomic approach, we found that the expression of 31 proteins related to neurodevelopment (e.g. CRMP-2, stathmin) and synaptic function (e.g. MUNC-18, NCS-1) is regulated by DISC1 in primary mouse neurons. Hence, this study reinforces the idea that DISC1 is a unifying regulator of both neurodevelopment and synaptic function, thereby providing a link between these two key anatomical and cellular circuitries.

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key polyphenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids was the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal and limited human studies for a dual preventative role of OO polyphenols in diabetes and cancer, especially that they share similar risk factors. Putative anti-oxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO phenolics, have produced paradoxical results making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anti-cancer and anti-diabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

Rapid urbanization, increasing population and increased industrialization to cater to demands of the growing population has imposed upon us a huge environmental cost. The significantly deteriorated air quality across the globe is associated with a direct and indirect impact on public health. While associated disorders such as chronic obstructive pulmonary diseases, heart failures are well documented, less is known about the biological basis of the process. We hypothesize that the worsening air quality may likely impact common systemic inflammatory processes, thus driving communicable and non-communicable diseases alike.Receptor mediated entry of particulate matter (PM2.5) results in activation of signaling cascades which culminate in production of inflammatory chemokine and cytokine responses, traversing through the blood mediating impacting not only on other organs but also dysbiosis of microflora. For the purpose of the review we choose tuberculosis (TB) as a model for communicable infectious disease and type 2 diabetes mellitus (T2DM) as a marker for non-communicable disorder. The increasing prevalence of these co-morbidities and the burdening of public health systems justifies this example. However the hypothesis may be applicable to other inflammation driven disorders also.

New corrosion inhibitor derived from coumarin-3-amine namely 3-((2-chlorobenzylidene)amino)coumarin was synthesized and characterized by CHN elemental analysis in addition to Fourier transform infrared and nuclear magnetic resonance techniques. The anti-corrosion ability of 3-((2-chlorobenzylidene)amino)coumarin to inhibit the impacts of corrosion has been demonstrated and damage reduction of the mild steel also. 3-((2-chlorobenzylidene)amino)coumarin, has been employed as a good corrosion inhibitor for mild steel in HCL solution. The efficiency of the inhibition was figured according to weight loss method and it was 74.6%.

In this study, we investigated the effects of Akebia quinata ethanol extract (AE), Akebia quinata sikhye (AS), and Akebia quinata water extract (AW) on alcohol-induced liver injury in rats. The hepatoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects of AE, AS, and AW were examined. Experimental animals were randomly divided into five groups: normal, ethanol, AE (10 mL/kg), AS (10 mL/kg), and AW (10 mL/kg). Each group was administered the respective treatment orally once per day for 21 days. CYP2E1 mRNA expression was significantly lower in the AE, AS, and AW groups than that in the ethanol group. Pro-inflammatory cytokines including cyclooxygenase-2, IL-6, and TNF-α increased significantly in the ethanol group but these increases were ameliorated with AE, AS, and AW treatment. Moreover, the expression of the apoptosis-associated proteins Bax, p53, procaspase-3, and PARP decreased after treatment with AE, AS, and AW. The expression of antioxidant enzymes including BCL-2, SOD, and GST slightly decreased in the ethanol group, but AE, AS, and AW treatment augmented their activities. AQ extracts and AS attenuated ethanol-induced increases in the levels of phosphorylated p-AKT, p-ERK, and p-JNK. These results demonstrate that AQ is a competence indicator for inhibiting alcoholic liver injury.

In order to comprehensively evaluate the employee satisfaction of mine occupational health and safety management system, an analytic method based on fuzzy analytic hierarchy process and 2- tuple linguistic model was established. Firstly, based on the establishment of 5 first- grade indicators and 20 second- grade ones, the weight of each indicator is calculated and validated by method of FAHP and root mean square model. Secondly, a path based on the time-ordered Weighted Averaging Operator (T-OWA) model is constructed. Finally, the model is validated by empirical analysis. The results demonstrate that the employee satisfaction of the mine occupational health and safety management system is of the “general” rank. The method including the comprehensive evaluation of employee satisfaction and the quantitative analysis of language evaluation information ensures the authenticity of the language evaluation information.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

The stability issues in the widely known organic inorganic halide perovskite, CH₃NH₃PbI_3, lead to the development of alternative halide double perovskite materials which get great attention in recent times. Although the stability issue seems promising, both materials and device performance of these photovoltaic materials remain inferior and challenging for improvements. Furthermore, the power conversion efficiency of single junction organic inorganic halide perovskite is now 24.2% and 29.15% for textured monolithic perovskite/silicon tandem solar cell, but for all-inorganic halide perovskite solar cell is 7.11% and halide double perovskite solar cells based on Cs₂AgBiBr₆ and Cs₂TiBr₆ is 2.8% and 3.3%, respectively, which is far less than 24.2% and 29.15%, respectively. This creates big question and concern that can both all-inorganic halide perovskite solar cell and halide double perovskites solar cells really be an acceptable alternatives to replace organic inorganic halide perovskite solar cells or lead based perovskite solar cells in the market in order to realize the sustainable practical applications? Not only this concern, but also there are many other big challenges facing by halide double perovskite solar cells. Such big challenges include: a) geometric constraints and limited integration with interfacial materials, b) dynamic disorder and a wide band gap and localized conduction band caused by cubic unit cell which restrains the interactions of orbitals, c) high processing temperature which may limit on the diverse applications, d) low electronic dimensionality making them less appropriate for single junction solar cell purpose and etc. Moreover, origin of electronic and optical properties such as the polarizability, the presence of molecular dipoles and their influence on the dynamics of the photo-excitations in the halide double perovskites remains unlock concern that need to be elucidated. Now, another big question is how to develop overcoming mechanisms for such challenges. Can we really overcome these current limitations faced by halide double perovskites so that we use them for sustainable commercialization? This research roadmap for performance improvement is suggested focusing on: materials surface and bulk engineering, band gap engineering, interfacial engineering, composition engineering, doping engineering, device architectural engineering, polar and domain order engineering. This was the reason that this review was developed in order to forward great contributions to the readers and commercial ventures.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

The Coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify host genetic factors influencing susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We genotyped 12 single nucleotide polymorphisms (SNPs) previously associated with the innate immune response in a total of 97 elderly (age >65 years) residents of three long-term care facilities located in the area of Barcelona, Spain. Individuals were PCR-tested during SARS-CoV-2 outbreaks between September and November 2020. SARS-CoV-2 PCR tests revealed infection in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2 seronegative until vaccination (January and February 2021). After adjusting for sex and age, we found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility: MMS19 nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2 infection was found for the 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in the gene encoding oligoadenylate synthetase (OAS). Our results indicate that MMS19 and IFIH1 genetic variants were associated with resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors.

Neurofibromas, rare benign tumors of the peripheral nerve sheath, present diagnostic challenges, particularly in diabetic patients with toe ulcers. This case involves a 55-year-old female with type 2 diabetes mellitus who developed an enlarging ulcer on her right second toe. The initial evaluation suggested a diabetic ulcer; however, advanced imaging revealed a mass-like lesion. Partial excision and biopsy confirmed a neurofibroma with spindle cells within the myxoid stroma and S100 protein expression. One month later, total excision and Z-plasty reconstruction were performed under general anesthesia. The patient’s postoperative recovery was uneventful, and the patient was discharged without complications. Follow-up revealed successful healing with no recurrence or functional issues. This case highlights the importance of considering neurofibromas in the differential diagnosis of diabetic toe ulcers to avoid misdiagnosis and ensure appropriate management.

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

COVID-19 infection in high-risk populations is fatal and has a poor prognosis, necessitating a test to determine the protectiveness of immune response. Antibody testing is necessary to determine the body's immune response to COVID-19 infection and also vaccination strategies. Among the various methods available, chemiluminescent immunoassay (CLIA) test is more widely used and accessible to determine antibody levels. This study aimed to determine the protection level of S-RBD SARS-CoV-2 IgG using CLIA compared to Surrogate Virus Neutralization Test (SVNT). The population of this study comprised all healthcare professionals who experienced S-RBD SARS-CoV-2 IgG antibody level examinations. S-RBD SARS-CoV-2 IgG antibody levels were examined using CLIA and SVNT. The cut-off was determined using Receiver Operating Characteristic (ROC) curve and AUC (Area Under the Curve) measurements were evaluated. The result showed a strong positive correlation between S-RBD SARS-CoV-2 IgG CLIA and SVNT with a value of r=0.933 and p <0.001. The value ≥37.29 BAU/mL was determined as the cut-off based on SVNT 30% inhibition level with sensitivity, specificity, positive, and negative predictive values of 96.5%, 90.9%, 96.5%, and 90.9%, respectively. A titer of antibodies greater than or equal to 37.29 BAU/mL with CLIA showed the presence of protective antibodies compared to SVNT.

Isolation, quarantine, and contact tracing were some of the most critical and commonly employed non-pharmaceutical interventions to control the COVID-19 pandemic. However, the effectiveness of these strategies after their implementation depends upon many factors such as the country's population, availability of sufficient resources to diagnose and effectively isolate the infected individuals, and feasibility, and acceptability of isolation and quarantine policy by the public. This narrative review aims to appraise the current evidence on the correct implementation strategies and shortcomings made in the isolation and quarantine strategies during the COVID-19 pandemic. PubMed, SCOPUS, EMBASE, and Web of Science citation index with the following keywords were searched: Pandemic, COVID-19, Coronavirus, Quarantine, and Isolation. The results showed that quarantine and isolation of COVID-19 patients were more effective than late adoption (5-fold versus 2.6-fold)’. Around 90% of outbreaks could have been managed if 80% of contacts were monitored, traced, and isolated within 4 days. For each new case of COVID-19, around thirty-six individuals should have been traced. When the percentage of individuals without symptoms is greater than 30%, isolation and contact tracing alone cannot contain the infection. The delay between the onset of symptoms and isolation is the most important factor determining whether an outbreak is controllable. The ideal day for testing should start on the 6th of the quarantine. However, this evidence is mostly based on mathematical modeling studies, and evidence for its effectiveness in real scenarios is required. Symptom-based isolation strategy should not be considered the sole criterion for considering isolation.

The relationship between nations is largely seen as a peripheral issue in the recent history of political philosophy and in the majority of discussions of political philosophy issues today. The idea of a universal natural state were countries are seen as essentially self-sufficient, functional units, and have been proposed to represent the relative lack of moral standards guiding relationships between nations. At one extreme of the tradition, international thought has substituted raison d'état being the highest norm for any universal laws governing relations between states, a view embodied by Machiavelli, Rodin, and others and Hobbes , The lack of supranational political powers has led to the conclusion that, even in cases where the possibility of international moral relationships has been acknowledged, such as in post-Grotian publications on international law, these ties are significantly weaker than in-tranational social bonds. The justification and aversion to war—the primary mode of social in-teraction in the natural condition of the world—is the only issue in the field of global relations to have received substantial theoretical study. Even though this disregard was justified in the past, a number of recent events force us to re-consider the "recalcitrance of international affairs to being theorized about."2. The growing gap between both prosperous and impoverished nations; the emergence of centers of economic in-fluence beyond the reach of effective state regulation; the emergence of severe food and energy shortages brought on, at least in part, by national governments' pursuit of disorganized and uncontrolled growth policies; the growing sensitivity of domestic Countries to the outside eco-nomic, political, and cultural events are some of these developments , requests from third-world nations for greater equal access to international politics and economy. To put it in terms more familiar to conversations about this topic, the rise of "low politics" in negotiation and "welfare questions" within global forums corresponds with the growing influence of transnational con-nections and international agreements on human well-being. Not because "high politics"—that is, the threat and prevention of war—has lost significance; rather, it is just one issue among many for which international cooperation is now required in order to find answers.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

: Intermittent fasting has drawn significant interest in the clinical research community due to its potential to address metabolic complications such as obesity and type 2 diabetes mellitus. Various intermittent fasting regimens include alternate-day fasting (24 hours of fasting followed by 24 hours of eating), time-restricted fasting (fasting for 14 hours and eating within a 10-hour window), and the 5:2 diet (fasting for two days and eating normally for the other five days). Intermittent fasting is associated with a reduced risk of type 2 diabetes mellitus-related complications and can slow their progression. The increasing global prevalence of type 2 diabetes mellitus highlights the importance of early management. Since prediabetes is a precursor to type 2 diabetes mellitus, understanding its progression is essential. However, the long-term effects of intermittent fasting on prediabetes are not yet well understood. Therefore, this review aims to comprehensively compile existing knowledge on the therapeutic effects of intermittent fasting in managing type 2 diabetes mellitus and prediabetes.

Background: Methotrexate (MTX) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible anti-tumoral potential of them in breast cancer (BC) cells. We aimed to determine the effects of MTX, which is widely used in clinical practice, on cell viability, Hypoxia-inducible factor (HIF) -1α, HIF-2α and prolyl 4-hydroxylase-transmembrane (P4H-TM) in BC cells (MCF-7) and health breast cell (HTERT-HME1) treated with MTX. Methods: Human healthy breast cells (HTERT-HME1) and BC cells (MCF-7) treated with MTX for 24 h, 48h, and 72 h, the effects of MTX on cell viability. Results: The cell viability and with half-maximal inhibitory concentration (IC50) values of of MTX treatment in healthy breast cells were determined to be higher than in MCF-7 cells. MTX showed higher cytotoxicity against MCF-7 cells. MTX significantly reduced cell viability values in HTERT-HME1 and MCF-7 cells. HIF-1α, HIF-2α, and P4H-TM levels was significantly higher in the MCF-7 group than the other groups. Morever, there was a moderate significant correlation between HIF-1α and HIF-2α levels and between HIF-1α and P4H-TM. Conclusions: MTX will show a further decrease in cell viability in long-term treatments of 48 and 72 hours, it is predicted that short-term use may be more appropriate. P4H-TM may be a novel regulator of hypoxia in BC cells. HIF-1α, a key protein responsible for the molecular mechanism of hypoxia in cells, is a key mediator between P4H-TM and hypoxia in MTX-treated cells. HIF-1α, HIF-2α, and P4H-TM values may be markers that can be used as a panel to differentiate BC from healthy women.

In the field of 2-D image processing and computer vision, accurately detecting and segmenting objects in scenarios where they overlap or are obscured remains a challenge. This difficulty is worse in the analysis of shoeprints used in forensic investigations because they are embedded in noisy environments such as the ground and can be indistinct. Traditional Convolutional Neural Networks (CNNs), despite their success in various image analysis tasks, struggle with accurately delineating overlapping objects due to the complexity of segmenting intertwined textures and boundaries against a background of noise. This study introduces employs the YOLO (You Only Look Once) model enhanced by edge detection and image segmentation techniques to improve the detection of overlapping shoeprints. By focusing on the critical boundary information between shoeprint textures and the ground, our method demonstrates improvements in sensitivity and precision, achieving confidence levels above 85% for minimally overlapped images and maintaining above 70% for extensively overlapped instances. Heatmaps of convolution layers were generated to show how the network converges towards successful detection using these enhancements. This research may provide a potential methodology for addressing the broader challenge of detecting multiple overlapping objects against noisy backgrounds.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to explore the mechanisms behind the vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactivated protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

(S)-1-Methyl-2-oxoimidazolidine-4-carboxylic acid 1 is an analog of (S)-pyroglutamic acid, a key component of naturally occurring peptide hormones and synthetic pharmaceutical candidates. Reaction of (S)-2-amino-3-(methylamino)propionic acid with COCl2 and aqueous NaHCO3 followed by ion exchange afforded 1, which was recrystallized from acetonitrile and then characterized by IR, 1H NMR, 13C NMR, polarimetry, elemental microanalysis, high resolution mass spectrometry and single crystal X-ray diffraction. The acid 1 crystallized in the orthorhombic chiral space group P212121 with cell constants a = 6.2275(4) Å, b = 8.3963(5) Å, c = 24.9490(14) Å. The X-ray crystal structure reveals that two distinct conformers of 1 occur at alternating positions within helices which are supported by hydrogen-bonding. Each molecule of 1 is linked to its two neighbors in the helix by a total of three hydrogen bonds and four molecules of 1 are contained within each turn of the helix. The pattern of hydrogen bonds illustrates a preference for the carboxylic acid group to act as a hydrogen bond donor and for the urea unit to be a hydrogen bond acceptor.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a single stranded RNA virus which has resulted in the Coronavirus Disease 2019 (COVID-19) pandemic and has infected millions of people all over the world. SARS-CoV-2 has been mutating rapidly resulting in the emergence of multiple variants to escape the host immune system mainly by mutations in its receptor binding domain (RBD) of the spike protein. This rapid evolution of the SARS-CoV-2 posed a great challenge regarding the efficacy and effectiveness of the current SARS-CoV-2 vaccines. The RBD and full-length spike of SARS-CoV-2 is the main target of the neutralizing antibodies. Many SARS-CoV-2 variants are considered to have the potential to escape from the host immune system. In this study, the RBD of Alpha, Beta, Gamma, Kappa and Omicron and the full-length spike of BA.1, BA.2, BA.3, BA.4/5, BQ.1.1 and XBB.1.5 Omicron variants were used as coating antigens in Enzyme Linked Immuno-Sorbent Assay (ELISA) to check the neutralization capability of COVID-19 convalescent sera from patients of first wave of infection occurring in Wuhan. Our results show that the currently circulating Omicron BQ.1.1, XBB.1.5 and previous Omicron BA.1, BA.2 and BA.4/5 do not show significant reduction in neutralization, while Omicron BA.3 and previous variants Alpha, Beta, Gamma, Kappa, and Omicron showed a significantly reduced neutralization when compared to the wild-type Wuhan strain. These results indicate patients recovering from natural infection of early original Wuhan strain may have the potential to resist infection of current circulating variants and the vaccines using the prototype antigen may still working for newly emerged variants.

Autism has been described as a gastrointestinal and neurological condition that is represented by impairments in language and social situations. Recently reported increases in the occurrence of Autism Spectrum Disorder (ASD) have resulted in increased research into the environmental differences between areas with a high occurrence, as in the “Western” diet populations, and a more locally derived diet population, wherein the rate appears to be significantly less. Thirty autistic children (USA) ages 6 to 21, were sampled at three different intervals: prior to any intervention, post-xylitol intervention, and post-probiotic intervention. The sampling consisted of buccal swabs for MITOSWAB testing, and saliva for metatranscriptomics to determine the entire range of microorganisms and the metabolome. In addition, a “Blue Zone” subject component that included 30 Colombian children, ages 6-16, and who were healthy and within normal behavior standards, also had buccal swabbing and salivary sampling performed for comparison along with 30 healthy (no history medications, illnesses, or behavior issues) USA children matched for age and gender. Saliva samples were analyzed metatranscriptomically and artificial intelligence was utilized to discern important differences in the microbiome that included bacteria, archaea, fungi, and viruses, and microbial functions. Significant differences were noted, and seen in the temporal data, demonstrating shifts that may have been precipitated by the interventions, with both the probiotics and the polyols. Particular bacterial strains were significantly more prevalent in the autism subject group including a strain that reduces neurotransmitters by enzymatic degradation. This provided supporting evidence to the hypothesis that the occurrence of autism may also be influenced by low Gamma Amino Butyric Acid (GABA) levels during development. Also, of interest was the un-expected finding that verbal skills dramatically increased in 6 of the 30 ASD subjects following xylitol supplementation.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene-expressed profiling identified significantly different neuregulin-2 (NRG2) gene expressions between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23±2.80) was significantly lower than that of controls (9.27±4.78, p < 0.001). Next, we resequenced all exons of NRG2 in other 349 ASD subjects, who were compared with super-controls from the Taiwan Biobank using case-control association analysis to determine the existence of mutations or single-nucleotide polymorphisms (SNPs). We identified three SNPs, including two noncoding ones, IVS3 + 13A > G (rs889022) and IVS9 + 32T > A (rs182642591), and one insertion/deletion (indel) SNP, named indel GCCCGGC, rs1323957797, in the NRG2 coding region. The genotype and allele frequency distribution of rs1323957797 significantly differed between ASDs and controls (p < 0.0001). Our findings showed significant differences in genotype and allele frequency distribution of the indel SNP, rs1323957797, located in the EGF-like domain region at the C-terminal of the NRG2 precursor protein. Together with our findings, the indel SNP mutation was significantly more common in ASDs than controls, leading to lower NRG2 expression than controls, influencing NRG2 function. Our study’s findings suggest that NRG2 is a susceptibility gene for ASD.

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

Dengue is one the most significant mosquito-borne viral diseases globally, with its prevalence extending across tropical and subtropical regions, exerting a considerable financial strain on health systems. Despite decades of research leading to the development of a vaccine implemented in endemic countries, its usage remains restricted to a fraction of the population at risk of contracting dengue. Due to these limitations, there is a growing focus on research aimed at unraveling the cellular mechanisms crucial for Dengue virus (DENV) infection to pinpoint potential host targets. Multiple studies propose a pivotal role of cytoskeletal remodeling in DENV infection. Specifically, DENV alters the organization of actin to facilitate viral entry, replication, and release. In this study, we investigated the involvement of the protein c-Abl, a kinase crucial in actin dynamics, in the context of DENV infection. Our findings suggest that either silencing or pharmacological inhibition of the kinase c-Abl leads to accumulation of dengue ENV protein in vitro, associated with actin remodeling. These results illuminate cellular mechanisms that could serve as potential therapeutic alternatives for dengue management.

SARS-CoV-2 is the Coronavirus responsible for the COVID-19 pandemic. Even though we are no more in a pandemic situation, people are getting infected some of them needing hospitalization, and a few of them die. Methods: We did a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we concentrated on the complete blood count, creatinine, and azotemia. The data was analyzed using ANOVA, Spearman correlation, and ROC analysis. They were divided into four groups based on their outcome: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients who after admission to the emergency section were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency section required intensive assistance); (4) the deceased group (patients that after the admission in the emergency section had a fatal outcome). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit, and red blood cell numbers by ANOVA according to their outcomes, particularly for the deceased group. Also, we found outcome correlations for eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet, and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an association between “classical” routine blood biomarkers and the severity of outcomes in Omicron patients.

Eutrophication, a global concern, impacts water quality, ecosystems, and human health. It’s crucial to monitor algal blooms in freshwater reservoirs, as they indicate the trophic condition of a waterbody through Chlorophyll-a (Chla) concentration. Traditional monitoring methods, however, are expen-sive and time-consuming. Addressing this hindrance, we developed models using remotely sensed data from the Sentinel-2 satellite for large-scale coverage, including its bands and spectral indexes, to estimate the Chla concentration on 149 freshwater reservoirs in Ceará, Brazil. Several machine learning models were trained and tested, including k-nearest neighbours, random forests, extreme gradient boosting, the least absolute shrinkage, group method of data handling (GMDH), and sup-port vector machine models. A stepwise approach determined the best subset of input parameters. Using a 70/30 split for the training and testing datasets, the best-performing model was the GMDH, achieving an R2 of 0.91, MAPE of 102.34%, and RMSE of 20.38 g/L, which are values consistent with the ones found in the literature. Nevertheless, the predicted Chla concentration values were most sensitive to the red, green, and near infra-red bands.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p&lt;0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Decarbonization of air mobility requires the decarbonization of its energy. While biofuels will play an important role, other low carbon energy carriers based on electricity are considered: battery electrification, liquid hydrogen (LH₂) or eFuel, a hydrogen-based energy carrier. Each energy carrier has its own conversion steps and losses and its own integration effects with the aircraft. These combinations lead to different energy requirements and must be understood to compare their cost and CO₂ emissions. Since they are all electricity-based, this study compares these energy carriers using the well to rotor methodology when applied to a standard Vertical Take-Off and Landing (VTOL) air mobility mission. This novel approach allows one to understand that the choice of the energy carrier dictates the propulsive system architecture, leading to integration effects with the aircraft which can significantly change the energy required, from 400 to 2665 kWh for the same mission. These deviations lead significant differences in CO₂ emissions and costs. Battery electrification is impacted by the battery manufacturing but has the lowest electricity consumption. It is an optimum solution but only until the battery weight can be lifted. In all scenarios eFuel is more efficient than LH₂. We conclude that carrying the most efficient molecule in an aircraft pays the extra energy cost spent on the ground. Finally, we found that for each of these energy carriers, it is the electricity carbon intensity and price which will dictate the cost and CO₂ emissions of an air mobility mission.

Mangifera indica (mango), a member of the Anacardiaceae family, is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, antiviral, cardiotonic, hypotensive, and anti-inflammatory effects. The present study delves the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin (STZ)-induced type 2 diabetic rats, concurrently investigating its phytoconstituents. EEMI's effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. It’s enzymatic inhibitory properties on carbohydrate digestion, glucose absorption, and free radicals were investigated using starch digestion, glucose diffusion and DPPH assay methods. In-vivo parameters including lipid profile and liver glycogen content were assessed on streptozotocin-induced type 2 diabetic rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake, oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL and HDL levels were observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugar. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes.

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, mechanism of infection, role of angiotensin-converting enzyme 2, host defense responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

To discover potential micro(mi)RNAs biomarkers of SARS-CoV-2 infection and disease progression, large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for SARS-CoV-2 infection (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. A totally of 1218 different miRNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Specific miRNA profiles are associated with COVID-19 prognosis in patients requiring oxygen flow.

Severe acute respiratory syndrome coronavirus 2 infects many people, but many infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus, and it is associated with liver injury and other complications leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for treatment of hospitalized patients with COVID-19 to improve time to recovery, reduce duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than 5 times the upper limit of normal in hospitalized patients with COVID-19 but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir and that a 5-day course of remdesivir seems to be safe in regards to hepatotoxicity.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of corona-virus disease 19 (COVID-19) and employs angiotensin-converting enzyme 2 (ACE2) as the recep-tor. Although the expression of ACE2 is crucial for cellular entry, we found that the interaction of ACE2 with the Spike (S) protein in the same cells led to its downregulation through degradation in the lysosomal compartment via the endocytic pathway. Interestingly, the ability of the S protein from previous variants of concern (VOCs) to downregulate ACE2 was variant-dependent and correlated with disease severity. The S protein from the Omicron variant, associated with milder disease, exhibited a lower capacity to downregulate ACE2 than that of the Delta variant, which is linked to a higher risk of hospitalization. Chimeric studies between the S proteins from the Delta and Omicron variants revealed that both the receptor-binding domain (RBD) and S2 subunit played crucial roles in the reduced ACE2 downregulation activity observed in the Omicron var-iant. In contrast, three mutations (L452R/P681R/D950N) located in the RBD, S1/S2 cleavage site, and HR1 domain were identified as essential for the higher ACE2 downregulation activity ob-served in the Delta variant than that in the other VOCs. Our results suggested that dysregulation of the renin-angiotensin system due to the ACE2 downregulation activity of the S protein of SARS-CoV-2 may play a key role in the pathogenesis of COVID-19.

Background: Mounting evidence supports the role of the endocannabinoid system in neurophysiology, includ-ing blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid re-ceptors can mitigate insults to the BBB during neurological disorders, like traumatic brain injury, cortical spreading depression and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Methods: Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid syn-thesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Results: In-hibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier in-tegrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. Conclusions: These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

Trichothecene mycotoxin T-2 toxin is an important environmental pollutant and poses a global threat to human and animal health. T-2 toxin could induce nephrotoxicity, however, the precise molecular mechanism remains unclear. In this study, the mice were intraperitoneally administrated with a single dose of 2 mg/kg T-2 toxin. The kidney function and ultrastructural observation were also assessed and found T-2 toxin exposure could cause kidney damage. Transmission electron microscopy showed a significant swelling and vacuolization of the mitochondria of renal cell. A total of 1122, 58, and 391 differential expression genes (DEGs) that were predominantly expressed in kidney tissues at 1 d, 3 d, and 7 d after T-2 toxin exposure, respectively. Early transcriptomic changes at 1 d after exposure were down-regulation of DEGs involved in the cell cycle, p53 signaling pathway, and cellular senescence, while up-regulation of DEGs referred to the ribosome pathway. The temporal variations in gene expression pattern in T-2 toxin exposure in mice kidney were presented and cellular metabolism was disturbed at the exposure recovery period with 7 d. In conclusion, this study, for the first time, provided a comprehensive comparative transcriptomic analysis of gene regulation in T-2 toxin exposure-induced nephrotoxicity at different temporal periods and explored the nephrotoxicity mechanism of T-2 toxin at the mRNA level.

Gelephu, located in the Himalayan region, has experienced one of the strongest development activities due to the suitable topography and geographic location, which has led to rapid urbanization. The main objective of the study is to perform land use land cover (LULC) mapping for Gelephu for 2016 and 2023 by a Random Forest (RF) classifier, using the Semi-automatic Classification Plugin (SCP) in QGIS and identify LULC changes. Furthermore, the study assessed the vegetation change dynamics within the study area by analysing the Normalized Difference Vegetation Index (NDVI) for 2016 and 2023. Additionally, the study characterized the resulting LULC change for Gelephu Thromde, a sub-administrative municipal entity, as a result of the notable intensity of the infrastructure development activities. The current study used a framework to collect Sentiniel-2 satellite data, which was then used for pre- and post-processing to create LULC and NDVI maps. The classification model achieved high accuracy, with an area under the curve (AUC) of up to 0.89. The corresponding LULC and NDVI statistics were analysed to determine the current status of the LULC and vegetation indices, respectively. The LULC change analysis reveals urban growth of 5.65% and 15.05% for Gelephu and Gelephu Thromde, respectively. The NDVI assessment shows significant deterioration in vegetation health with a 75.11% loss of healthy vegetation in Gelephu between 2016 and 2023. This research provides the first version of LULC and NDVI maps of Gelephu. The analysis results indicate possible future implications on sustainable development management in Gelephu Bhutan.

The capability of antibodies to neutralize different SARS-CoV-2 variants varies among individuals depending on the previous exposure to wild-type- or Omicron-specific immunogens by mono- or bivalent vaccinations or infections. Such profiles of neutralizing antibodies (nAbs) usually have to be assessed by laborious live virus-neutralization tests (NTs). We therefore analyzed whether a novel multivariant surrogate virus neutralization test (sVNT) (adapted from a commercial microarray) that quantifies the antibody-mediated inhibition between the receptor angiotensin-converting-enzyme 2 (ACE2) and variant-specific receptor-binding domains (RBDs) can assess the neutralizing activity against SARS-CoV-2 wild-type, Delta Omicron BA.1, BA.2 and BA.5 (sub-) variants after a booster with Omicron-adapted bivalent vaccines in a manner similar to live-virus NTs. Indeed, by using the live-virus NTs as a reference, we found a significant correlation between the variant-specific NT titers and levels of ACE2-RBD binding inhibition (p < 0.0001, r ≤ 0.78 respectively). Furthermore, the sVNTs identified higher inhibition values against BA.5 and BA.1 in individuals vaccinated with Omicron-adapted vaccines than in those with monovalent wild-type vaccines. Our data thus demonstrate the ability of sVNTs to detect variant-specific nAbs following a booster with bivalent vaccines.

Boeremia exigua var. exigua is a recurrent pathogen causing root rot in industrial chicory. Currently, there is no chemical or varietal control for this disease, and thus management strategies need to be developed. This study determined the biocontrol effect of strains of Pseudomonas protegens bacteria with antimicrobial compounds on the fungus B. exigua var. exigua under in vitro, in vivo and field conditions. In addition, root colonization by these bacteria was estimated by molecular analysis. Eighteen isolates of Pseudomonas spp were evaluated and the strains that showed the greatest in vitro inhibition of fungal mycelial growth (mm), Ca10A and ChB7, were selected. Inoculation with the strain ChB7 showed less severity (necrotic area) under in vivo conditions (root trials) compared to the control inoculated with the pathogen (P≤0.05). The molecular analysis revealed that root colonization of plants grown in pots was equal or greater than 70%. Similar levels were observed in the field trials conducted in Selva Negra and Canteras experimental stations (2015-16 season), with values ranging from 85.7 to 70.5% and from 75.0 to 79.5%, respectively. Regarding yield (ton ha-1), values were higher in the treatments inoculated with strains Ca10A and ChB7 (P≤0.05) in both experimental sites, while a lower incidence and severity of root rot were observed in Selva Negra. These results suggest that the Chilean strains of P. protegens are a promising tool for the control of root diseases in industrial chicory.

Dengue virus serotype 2 (DENV-2) is responsible for dengue epidemics on a global scale and is recognized for being associated with severe cases of the disease. This study conducted the phylogenetic investigation of DENV-2 in the Northern region of Brazil. DENV-2 isolates from 2017 to 2021, originating from Northern Brazilian states, were selected. Only one lineage (I) of the Asian-American genotype and one lineage (5) of the cosmopolitan genotype were observed. All sequences of the Asian-American genotype used in this study were segregated into a paraphyletic subgroup aligned with sequences from an American clade. These results indicate a probable geographic link starting from Puerto Rico. Additionally, sequences from Acre were identified and grouped into a monophyletic clade of the cosmopolitan genotype. These results indicate the cocirculation of two DENV-2 distinct lineages: Lineage 1, Asian-American genotype (probable origin from Puerto Rico); Lineage 5, cosmopolitan genotype (probable origin from Peru). Our results provide important data regarding the study of DENV genotypes and lineages distribution, as well as opening up possibilities for probable introduction and dissemination routes.

Abstract: The COVID-19 pandemic significantly disrupted global healthcare systems. The impacts of SARS-CoV-2 infection on urticaria and its management are unknown. To collect information about patients with urticaria infected with SARS-CoV-2 and to investigate the impact of SARS-CoV-2 infection on urticaria severity, course, and treatment to better support recovery. This was a questionnaire-based study of patients with urticaria infected with SARS-CoV-2. Changes in urticaria severity (measured with the urticaria activity score (UAS)), course, and treatment were assessed before, during, and after SARS-CoV-2 infection. Mean (± SD) UAS scores were 5.17 ± 1.67, 4.23 ± 1.98, and 4.37 ± 1.93 before, during, and after SARS-CoV-2 infection, respectively (F = 8.839, p < 0.01). The median (IQR) wheal score was 0.464 (0.464, 0.763), 0.464 (0.138, 0.763), and 0.464 (0.138, 0.763) before, during, and after infection, respectively (Kruskal-Wallis H-test, H=12.230, p = 0.02). The median (IQR) pruritus score was 0.695 (0.395, 0.695), 0.394 (0.123, 0.695), and 0.394 (0.123, 0.695) before, during, and after infection, respectively (Kruskal-Wallis H-test, H = 21.001, p < 0.01). Within the limitations of a questionnaire study, urticaria appears to improve during SARS-CoV-2 infection, worsens slightly after recovery, and the frequency of Western medicine use increases.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019, it has spread rapidly, and many coronavirus disease (COVID-19) cases have occurred in Gwangju, South Korea. Viral mutations following the COVID-19 epidemic have increased interest in the characteristics of epidemics in this region, and pathogen genetic analysis is required for infection control and prevention. In this study, SARS-CoV-2 whole-genome analysis was performed on samples from patients with COVID-19 in Gwangju from 2020 to 2022 to identify the trends in COVID-19 prevalence and to analyze the phylogenetic tree of dominant variants. B.41 and B.1.497 prevailed in 2020, the early stage of the COVID-19 outbreak; then, B.1.619.1 mainly occurred until June 2021. B.1.617.2, classified as sublineage AY.69 and AY.122, occurred continuously from July to December 2021. Since strict measures to strengthen national quarantine management had been implemented in South Korea until this time, mutations phylogenetic analysis was also able to infer the epidemiological relationship between infection transmission routes. Since the first identification of the Omicron variant in late December 2021, the spread of infection has been very rapid, and weekly whole-genome analysis of specimens has enabled us to monitor new Omicron sublineage occurring in Gwangju. Our study suggests that conducting reginal surveillance in addition to nation-level genomic surveillance will enable more rapid and detailed variant surveillance, which will be helpful in the overall prevention and management of infectious diseases.

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.

Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1a (HIF1a) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Chronic myeloid leukemia (CML) is the most common form of leukemia in adults and accounts for approximately 15% of all leukemia cases. The etiology of this disease is based on the presence of the oncogenic Bcr/Abl fusion protein, which has dysregulated tyrosine kinase activity. This pathological condition is the result of a chromosomal translocation between chromosomes 9 and 22 leading to the formation of the Philadelphia chromosome (Ph). Clinical establishment of targeted therapy with Abl kinase inhibitors (AKIs) has been observed in the treatment of CML. Therapy resistance in patients with CML is due to genetic alterations in the cells of CML, specifically affecting the Bcr/Abl oncoprotein. Acquired resistance of CML patients to tyrosine kinase inhibitors (AKIs) has also been associated with the tumor microenvironment (TME). This study aimed to examine the role of hypoxic conditions in the development of chemoresistance to certain AKIs in CML. The findings of our study indicate that exposure to hypoxic conditions leads to a substantial increase in chemoresistance to crizotinib, while only resulting in a slight increase in chemoresistance to imatinib. It is worth noting that both drugs effectively block Bcr/Abl function. Furthermore, it was observed that the inclusion of the JAK1/2 inhibitor ruxolitinib resulted in an augmentation of chemoresistance to crizotinib in the context of hypoxia. Overexpression of hypoxia-inducible factor 1 (HIF1) and silencing of JAK2 confirmed that the two proteins cooperate in mediating chemoresistance to crizotinib in CML cell lines. It is noteworthy that the compound 2-methoxy estradiol (2ME2), which is a metabolite of estradiol lacking estrogenic activity, has shown efficacy in reinstating the sensitivity of CML cells to crizotinib in the presence of hypoxic circumstances. Additionally, when used in conjunction with a JAK2 inhibitor, 2ME2 exhibited activity in restoring crizotinib sensitivity in CML cells. The findings of our study underscore the significance of selectively targeting elements of the HIF1α pathway in order to achieve total eradication of chronic myeloid leukemia (CML) cells.

Severe infection from the SARS-CoV-2 virus is associated with various clinical findings, including hematological manifestations. Thrombotic events or a tendency to develop thrombotic events also characterize severe COVID-19 disease and may lead to death. Vitamin D is known to have immunomodulating properties and to enhance the body defense system against invading pathogens and to have immunostimulatory properties as far as the innate immune response is concerned. The aim was to measure 25(OH)D3 levels in patients hospitalized for severe COVID-19 infection, to explore the relationship between 25(OH)D3 and outcome and to investigate the relationship between 25(OH)D3 levels, CRP, ferritin, d-dimers and fibrinogen levels in this cohort. In a cohort of 88 patients hospitalized for severe infection from the SARS-CoV-2 virus and a control group matched for age and sex the levels of 25(OH)D3 were measured. In the same cohort CRP, ferritin, d-dimer and fibrinogen levels were also analyzed. Levels of 25(OH)D3 were 17.36±8.80 ng/ml (mean±SD) as compared with 24.34±10.34 ng/ml, in patients with severe SARS-CoV-2 infection and the control group, respectively, p<0.001 (Student’s t test). The levels of 25(OH)D3 were found to be significantly related to outcome, i.e. survival as opposed to non-survival, as more patients with 25(OH)D3 deficiency (0-10 ng/ml) and insufficiency (10-20 ng/ml) had a fatal outcome as compared with those with vitamin D sufficiency, p<0.001, chi-square test, p<0.001, Fischer’s exact test. Levels of 25(OH)D3 were inversely related to CRP, ferritin, d-dimer and fibrinogen levels, p<0.001, linear regression analysis, beta coefficient of variation, -0.176, -0,160, -0.178, -0.158, respectively. Vitamin D deficiency observed in severe SARS-CoV-2 infection was related to the disease outcome. Increased ferritin levels, and increased thrombotic markers, namely d-dimer and fibrinogen levels were observed in the patients and their concentration was also inversely related to vitamin D. We showed that vitamin D levels were low in hospitalized patients with severe SARS-CoV-2 infection and also inversely related to CRP, ferritin, d-dimer and fibrinogen concentration. It is proposed that vitamin D levels may be an index of severity in the context of SARS-CoV-2 infection.

The newly emerged variants of SARS-CoV-2 created a potential threat among societies and highlighted one of the significant concerns in facing the pandemic. SARS-CoV-2 variants harboring mutations in the structural protein, especially in the RBD domain of spike protein, have raised concern about potential immune escape. The spike protein of SARS-CoV-2 play a vital role in infection and is an important target for neutralizing antibodies. The mutations that occur in the structural proteins, especially in the spike protein, lead to changes in the virus attributes of transmissibility, an increase in disease severity, a notable reduction in neutralizing antibodies generated, and thus a decreased response to vaccines and therapy. The immune response against SARS-CoV-2 has been reported mainly through innate immune responses rather than adaptive immune responses. SARS-CoV-2 invades the host's innate immunity, possibly through inducing cytokine storm, impairing type I IFN responses, and suppressing antigens presentation to T cells. Therefore, the adaptive immune response is required to combat SARS-CoV-2 infection. The SARS-CoV-2 infections activated both arms of adaptive immunity; humoral and cell-mediated immunity. The observed multiple mutations in the RBD domain of the spike protein compromised the adaptive immune response and showed immune escape because it increases the affinity of spike protein binding with the ACE-2 receptor of host cells and increases resistance to neutralizing antibodies. Cytotoxic T-cell responses are crucial in controlling SARS-CoV-2 infections from the infected tissues and clearing them from circulation. CD8+cytotoxic T cells identify and directly kill the infected cells by releasing soluble mediators perforin and granzymes. The functional exhaustion of cytotoxic T cells may increase the severity of the disease. The expression of activation markers of T cells could indicate hyperactivation or functional exhaustion; the exact implication is not yet understood in SARS-CoV-2 infections. These mutations at critical residues influence the antigenic profile of SARS-CoV-2, which may evade the immune responses and thus reduce the immunogenicity and efficacy of vaccines. Therefore, the spike protein may be recognized as a primary target for vaccines and drugs. This review article summarizes the impact of mutations in the spike protein of SARS-CoV-2, especially mutations of RBD, on immunogenicity, immune escape, and vaccine-induced immunity, which could potentially contribute to future studies focusing on vaccine design and immunotherapy.

Streptococcus suis serotype 2 is an important swine bacterial pathogen causing sudden death, septic shock, and meningitis. However, serotype 2 strains are phenotypically and genotypically heterogeneous and composed by a multitude of sequence types (STs) whose distribution greatly varies worldwide. It has been previously shown that lipoprotein (LPP) maturation enzymes diacylglyceryl transferase (Lgt) and signal peptidase (Lsp) significantly modulate the inflammatory host response and play a differential role in virulence depending on the genetic background of the strain. Differently from Eurasian ST1/ST7 strains, the capsular polysaccharide of a North American S. suis serotype 2 ST25 representative strain only partially masks sub-capsular domains and bacterial wall components. Thus, our hypothesis is that since LPPs would be more surface exposed in ST25 strains than in their ST1 or ST7 counterparts, the maturation enzymes would play a more important role in the pathogenesis of the infection caused by the North American strain. Using isogenic Δlgt and Δlsp mutants derived from the wild-type ST25 strain, our studies suggest that these enzymes do not seem to play a role in the interaction between S. suis and epithelial and endothelial cells, regardless the genetics background of the strain used. However, a role in the formation of biofilms (also independently of the STs) has been demonstrated. Moreover, the involvement of LPP dendritic cell activation in vitro seems to be somehow more pronounced with the ST25 strain. Finally, the Lgt enzyme seems to play a more important role in the virulence of the ST25 strain. Although some differences between STs could be observed, our original hypothesis that LPPs would be significantly more important in ST25 strains due to a better bacterial surface exposition could not be confirmed.

Vaccination has proven highly effective against severe acute res-piratory syndrome coronavirus 2 (SARS-CoV-2), but the long-term immunogenicity and the functional preserved im-mune responses of vaccines are needed to inform evolving evi-dence-based guidelines for boosting schedules. We enrolled 205 healthcare workers into a cohort study; all had received three doses of BBIBP-CorV (China Sinopharm Bio-Beijing Company) inactivated vaccine. We assessed SARS-CoV-2 specific binding antibodies, neutralizing antibody, and peripheral T and B cell responses. We demonstrated that more robust antibody re-sponses to SARS-CoV-2 were elicited by booster immunization compared to primary vaccination. Neutralizing antibody titers to SARS-CoV-2 Omicron variant were also efficiently elevated post homologous vaccine booster despite in a lower titer compared to the prototype stain. In addition to S specific humoral and cellular immunity, BBIBP-CorV also induced N-specific antibody and ef-fector T cell responses. The third-dose vaccination led to further expansion of critical polyfunctional T cell responses, likely an essential element for vaccine protection. In particular, a func-tional role for Tfh cell subsets in immunity was suggested by the correlation between both CD4+Tfh and CD8+Tfh with total anti-body, IgG, B cell responses and neutralizing antibodies. Our study details the humoral and cellular responses generated by the BBIBP-CorV booster vaccination in a seven-month follow up study. There is a clear immunologic boosting value of homolo-gous inactivated SARS-CoV-2 vaccine boosters, a consideration for future vaccine strategies.

The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/ prostaglandin E2 (PGE2) up-regulated by SiNPs toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNPs-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3‑kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.

Since the onset of the COVID‐19 pandemic, humanity has experienced the spread and circulation of several SARS-CoV-2 variants that differed in transmissibility, contagiousness, and the ability to escape from vaccine-induced neutralizing antibodies. However, issues related to the differences of variant-specific immune responses, remain insufficiently studied. The aim of this study was to compare the parameters of the humoral immune responses in two groups of patients with acute COVID-19 who were infected during the circulation period of the D614G and the Delta variants of SARS-CoV-2. Sera from 48 patients with acute COVID-19 were tested for SARS-CoV-2 binding and neutralizing antibodies using six assays. We found that serum samples from the D614G period demonstrated 3.9‐ and 1.6‐fold increase in RBD- and Spike‐specific IgG binding with Wild type antigens compared with Delta variant antigens (p &lt; 0.01). Cluster analysis showed the existence of two well-separated clusters. The first cluster mainly consisted of D614G period patients and the second cluster predominantly included patients from Delta period. The results thus obtained indicate that humoral immune responses in D614G- and Delta-specific infections can be characterized by variant-specific signatures. This can be taken into account when developing new variant-specific vaccines.

Firocoxib is a non-steroidal anti-inflammatory drug specifically formulated for veterinary medicine and selectively acts on inhibiting the cyclooxygenase 2 enzyme(COX-2). This study aimed to evaluate the possible adverse effects of administering oral therapeutic firocoxib on gastric mucosa, hematological parameters, coagulation cascade, and hepatic and renal biochemistry in healthy horses. Nine clinically healthy Arabian horses, approximately nine years old, received 0.1mg/kg of oral firocoxib for 14 days. Before beginning treatment, a gastroscopic examination was conducted, and venous blood samples were obtained for laboratory tests on D0. Follow-up blood samples and gastroscopic examinations were taken on D7 and D14 after starting treatment and one week after completing treatment on D21. No changes were found in the gastroscopic and hematological tests. Additionally, coagulation and serum biochemistry levels remain between normal values for this particular species. However, the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT) indicate reduced blood coagulation capacity, which contradicts the expected effect of treatment with selective COX-2 inhibitors, as these drugs theoretically promote coagulation. Administering Firocoxib to horses is safe as it does not cause any significant adverse reactions. Therefore, it is a suitable option for managing inflammatory conditions in these animals.

Objectives: The aim of our study was to evaluate patients after suicide attempts treated at the Department of Trauma Surgery for Children before and after the outbreak of the Covid-19 pandemic. Material and methods: Retrospective review of the medical database at equal time intervals of 24 months to identify patients treated before and after the COVID-19 was done. Thorough analysis including injury mechanism, medical procedures, history of previous mental disorders or suicidal behavior was performed. Furthermore, results were compared with the Polish police suicide statistics. Results: Based on our retrospective review we found 4 patients treated in our department before the pandemic and 10 patients treated after COVID-19 outbreak. The group before SARS-Cov-2 era consisted of three girls and one boy with a mean age of 14.97 (12.7-17.6). The group treated in the pandemic crisis consisted of 8 boys and 2 girls, the mean age was 15.49 (10.8-17.2). In the pre-COVID-19 group, 2 out of 4 patients had received psychiatric treatment before, but none had attempted suicide before. In the COVID-19 group, 6 out of 10 patients had previously received psychiatric treatment, moreover 3 of them attempted suicide before. Based on our analysis, the number of individuals who displayed suicidal attempts has raised. Between 2018 and 2021 the largest number of suicides concerned the 13-18 y.o. group, both for the Silesian Voivodeship (H=9.374; p=0.0092) and for the whole country (H= 10.203; p=0.0061). Conclusions: 1. Results of our study indicate that the pandemic may have caused a wide range of negative mental health consequences for young individuals; 2. During the SARS-Cov-2 era, we observed an alarming 2.5-fold increase in the number of patients treated after suicide attempts at the children's orthopedic trauma department; 3. Suicide attempts in children are often related with high energy trauma.

Introduction: The need for therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remains unmet. Previous work has shown that a combination of three aromatic plants’ essential oil (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticosa Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care. Methods: 69 adult patients were included in a clinical, Proof-of-Concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention and control group) during three study periods (IG2020, n=13, IG2021/22, n=25 and CG2021/22, n=31). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture, was administered daily for 14 days, per os in the intervention group, while the control group received usual care. Results: The PoC study, found that the number and frequency of general symptoms, including general fatigue, weakness, fever and myalgia, decreased following CAPeo administration. The average presence (number) of symptoms decreased in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1) by Day 7 compared to Day 1, representing a significant decrease in cumulative presence in IC (-3.3 vs. -0.9, p<0.001; η2=0.20) on Day 7 and on Day 14 (-4.2 vs. -2.9, p=0.027; η2=0.08). Discussion/Conclusion: Our findings suggest that CAPeo, possesses potent antiviral activity, in addition tο the Influenza A and B and the human rhinovirus HRV14 strains against SARS-CoV-2. The early and effective impact in alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for mild COVID-19 patients

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all the cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays of PBMC. We included 5 nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT to at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

Control charts have been widely used for monitoring process quality in manufacturing and play an important role in triggering a signal in time when detecting a change in process quality. Many control charts in literature assume that the in-control distribution of the univariate or multivariate process data is continuous and not categorical. This research develops two exponentially weighted moving average (EWMA) proportion control charts for monitoring a process with multinomial proportions when considering both large and small sample sizes. For a large sample size , the charting statistic depends on the well-known Pearson χ2 statistic, and the control limit of the EWMA proportion chart is determined by an asymptotical chi-square distribution. For a small sample size, we derive the exact mean and variance of the Pearson χ2 statistic. Hence, the exact EWMA proportion chart is determined. The proportion chart can also be applied to monitor the distribution-free continuous multivariate process as long as each categorical proportion associated with specification limits of each quality variable is known or estimated. Lastly, we investigate the detection performance of the proposed EWMA proportion chart by numerical analyses. Real data analysis demonstrates the beneficial application of the proposed EWMA proportion charts.

Background The main aim of reconstructive surgery (RS) is to restore the integrity of soft tissues damaged by trauma, surgery, congenital deformity, burns or infection. Microsurgical techniques consist of harvesting tissues that are separated from the vascular sources of the donor site and anastomosed to the vessels of the recipient site. In these procedures, there are some preoperative modifiable factors that have the potential to influence the outcome of the flap transfer and its anastomosis. Methods Chronic inflammatory anaemia (ACD) is a constant condition in patients who have undergone RS and correlates with the perfusion of the free flap. In RS, it is important to maintain good tissue oxyporesis, avoiding blood hyperviscosity. From January 2017 to September 2019, we studied 16 patients (16 males, mean age 38 years) who underwent microsurgical procedures for RS. Haemoglobin (Hb) levels, Corpuscular Indexes, Transferring saturation (TSAT) ferritin concentrations and creatinine clearance have been measured the first day after surgery (T0), after the first week (T1) and after five weeks (T2). At T0 all patients showed low hemoglobin levels (average 7.4 g/dl, STD 0,71range 6,2-7,4 g dL-1), with an MCV of 72, MCH 28, MCHC 33, RDW 16, Sideremy 35, Ferritin 28, Ret% 1,36, TRF 277 and Creatinine Clearance 119. . We assessed all patients for clinical status, medical history and comorbidities before starting therapy. Results. In collaboration between the two departments, we started a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, on the second day after surgery. Thirteen patients received ESAs and FCM (500-1000 mg per session), three patients received ESAs and iron gluconate (1 vial every other day). No patients received blood transfusions. No side effects were observed and, most importantly, no limb or flap rejection. Conclusions Preliminary data from our protocol show an optimal therapeutic response in a surgical setting with limited data in the scientific literature. The enrolment of further patients will allow us to validate this therapeutic protocol with statistically significant data.

Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of RIPOVAC study, between December 2021 and January 2022, eight months after the second dose, 389 voluntary, immunocompetent, non-pregnant healthcare workers received a booster dose of SARS-CoV-2 vaccine, and a serum sample was obtained. Two groups of patients were established: with and without previous SARS-CoV-2 infection. In order to quantify anti-S1 IgG (AU/mL) we used CMIA (Abbott). All the health workers were anti-S IgG positive 8 months after receiving the booster dose of the vaccine, with a mean of 17040 AU/mL. In 53 patients without previous infection, antibody levels had increased by a mean of 10762 AU/mL. This figure is 7 times higher than the one produced after the second dose (1506 AU/mL). The booster dose produces a robust elevation of the antibody level, which persists at 8 months with levels up to values significantly higher than those reached after the second dose, that allow to predict a persistence of more than one year. The study demonstrates the efficacy of the booster dose of anti-SARS-CoV-2 vaccines.

Rapid emergence of evasive SARS-CoV-2 variants is an on-going challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform on the sufficiency of the breadth of antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. Traditional analysis of neutralization titers against WT, Alpha, Beta, Delta, Omicron BA.1 and BA.4/BA.5 showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen.

A novel synthetic strategy is disclosed to prepare a new class of metalorganic copolymers which contain iron(II) clathrochelate building blocks by employing a mild and cost-effective copper-catalyzed [4 + 2] cyclobenzannulation reaction, using three specially designed diethynyl iron(II) clathrochelate synthons. The target copolymers CBP1-3 were isolated in high purity and excellent yields as proven by their structural and photophysical characterization, namely, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and UV-vis absorption and emission spectroscopies. Thermogravimetric analysis (TGA) of CBP1-3 reveals excellent chemical stability. Investigation of the adsorption properties of the target copolymers towards the carcinogenic methyl red dye from aqueous solution reveals a quantitative uptake in 30 minutes. Isothermal adsorption studies disclose that methyl red uptake from aqueous solution follows Langmuir model for all the target copolymers reaching a maximum adsorption capacity (qm) of 431 mg g‒1, whereas kinetic investigation reveals that the adsorption follows pseudo first-order with an equilibrium adsorption capacity (qe,cal) of 79.35 mg g‒1 and whose sorption property was sustained even after its reuse several times.

Robot Operating System 2 (ROS 2) is a robotic software that uses a set of Quality of Service (QoS) policies to manage the quality of robot data transmissions in a network, such as the RELIABLE and KEEP_LAST options. In ROS 2 node communication, the RELIABLE connection guarantees that all message data can be properly sent from the publisher to the subscriber. However, strict reliability is not guaranteed if the RELIABLE connection uses the KEEP_LAST option to transmit the robot data in the publish-subscribe communication. This study aims to analyze the efficiency of local cache, cache control, and QoS balancing optimization to improve ROS 2 node communication when using the RELIABLE and KEEP_LAST options to transmit multi-robot data in Aggregated Robot Processing (ARP) architecture. Our idea in local cache and cache control is to streamline the sensor data output before processing it when the sensor device produces the data with the same value in a row. Furthermore, QoS balancing optimization aims to balance the DEPTH and DEADLINE QoS configuration to determine the rates and buffer size in ROS 2 node communication. This study shows that combining local cache and QoS balancing optimization improves multi-robot data transmission and cooperation in ARP architecture.