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1.
Bioengineering ; 9(4):135, 2022.
Article in English | ProQuest Central | ID: covidwho-1809682

ABSTRACT

Footwear is among the most important equipment in sports to decrease injuries and enhance performance during exercise. In this study, we investigated differences in lower extremity plantar pressure and muscle activations during jump rope activities. Ten participants performed jump rope under two landing conditions with different footwear. A force platform (AMTI, 1000 Hz), a Novel Pedar-X system (Nove, 100 Hz), and a wireless electromyography (EMG) system (Noraxon, 1500 Hz) were used to measure biomechanical parameters during the jump rope exercise. Vertical ground reaction forces (vGRF), plantar pressure, and lower extremity muscle activations were analyzed. One-leg landing resulted in a significantly greater vGRF and shorter fly time than two-leg landing (p < 0.05). A significantly higher peak pressure and lesser toe (LT) area pressure was shown with the jumping shoe (all p < 0.05), but lower plantar pressure resulted in the middle foot area (p < 0.05). The EMG results of tibialis anterior (TA) were significantly greater with one-leg landing (all p < 0.05) during the pre- and background activity (BGA) phases. The results suggest that plantar pressure distribution should be considered when deciding on footwear during jump rope exercises, but care should be taken with regards to recovery after repeated collisions and fatigue. The jumping shoe provides benefits in terms of decreased plantar pressure sustained during jump rope exercises.

2.
J Nurs Manag ; 2022 Apr 10.
Article in English | MEDLINE | ID: covidwho-1784703

ABSTRACT

AIMS: To investigate the situation and perceptions of nursing directors about emergency nursing staff deployment in designated hospitals during the pandemic of COVID-19 in mainland China. BACKGROUND: The pandemic of COVID-19 has significantly depleted healthcare resources, leading to increased burden of nursing care and staffing, and exacerbating the crisis in healthcare facilities. Currently, how to effectively plan and schedule nursing staffing in the pandemic still remains unknown. METHODS: From July 14, 2020, to September 8, 2020, 62 nursing directors of designated hospitals in mainland China were invited to participate in a cross-sectional online survey for their perceptions of nursing human resource allocation during the pandemic of COVID-19. RESULTS: A total of 55 valid questionnaires were collected, showing that 96.36% of the hospitals had emergency nursing organizations and management systems during the pandemic, 96.36% had well-established scheduling principles for nursing human resources, and 54.55% of hospitals had human resource scheduling platforms. All the hospitals had trained emergency nursing staff in infection control (55,100%), work process (51, 92.73%), and emergency skills (50, 90.91%). Most of the participants were satisfied with the nursing staffing deployments at their institutions (52, 94.55%). However, more than two-thirds of them believed that their human resource deployment plans need further improvements (39, 70.91%). CONCLUSIONS: Most of the designated hospitals investigated had established emergency nursing organizations, and management systems, and related regulations for the epidemic. However, the contents metioned above still needs to be further standardized. IMPLICATIONS FOR NURSING MANAGEMENT: The surge of patients in the epidemic was considerable challenge for the emergency capacity of hospitals. In the future, we should pay more attention to the following aspects: building emergency nursing staffing platforms, increasing emergency human resource reserves, establishing reliable communication channels for emergency response teams, improving the rules and regulations of emergency human-resource management, offering more training and drills for emergency-related knowledge and skills, and giving more focus on bio-psycho-social wellbeing of nurses.

3.
BMC Infect Dis ; 22(1): 201, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1779609

ABSTRACT

BACKGROUND: China is one of 30 countries with a high tuberculosis (TB) burden, and poor adherence to TB treatment is one of the biggest challenges for TB control. We aimed to explore the barriers and facilitators of treatment adherence among drug-sensitive tuberculosis (DS-TB) patients under the "Integrated model" in Western China, to provide evidence-based treatment and control regimens for DS-TB patients to improve adherence behaviours. METHODS: Both qualitative and quantitative research methods were used to explore the factors associated with self-reported adherence (SRA) behaviours. Questionnaire surveys with DS-TB patients and in-depth interviews with leaders from the Centers for Disease Control and Prevention (CDC) and community health sectors (CHCs), healthcare workers (HCWs) from CHCs, and DS-TB patients were conducted. RESULTS: A total of 459 eligible patients were included in the quantitative survey, and two patients and 13 healthcare providers were included in the in-depth interviews. The percentage of patients who experienced a missed dose, lack of follow-up sputum examination, and interrupted treatment were 19.0%, 11.3%, and 9.2%, respectively. Patients aged 20-39 had a higher risk of missed dose [OR (95% CI): 2.302 (1.001-5.305)] and a lower risk of interrupted treatment [OR (95% CI): 0.278 (0.077-0.982)] than patients more than 60 years. Patients who were of Han ethnicity (OR [95% CI]: 0.524 [0.301-0.912]) received psychological support (OR [95% CI]: 0.379 [0.144-0.998]) from their family and had a lower risk of missed doses. Patients who had drug side effects had a higher risk of interrupted treatment (OR [95% CI]: 2.587 [1.237-5.412]). Patients who possessed higher knowledge had a lower risk of lack of follow-up sputum examination [OR (95% CI): 0.817 (0.673-0.991)]. The results of the qualitative study also reported that patients' poor TB knowledge was the main reason for their non-SRA behaviours. CONCLUSIONS: Patient-centred strategies should be implemented to improve health literacy and strengthen psychological support. More effective case management should be designed and implemented based on different patient characteristics to improve adherence behaviours in further studies.


Subject(s)
Antitubercular Agents , Tuberculosis , Adult , Antitubercular Agents/therapeutic use , China , Humans , Self Report , Surveys and Questionnaires , Tuberculosis/drug therapy , Young Adult
4.
J Clin Microbiol ; : e0237421, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1765076

ABSTRACT

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with enhanced transmissibility, pathogenicity, and immune escape ability have ravaged many countries and regions, which has brought substantial challenges to pandemic prevention and control. Real-time reverse transcriptase PCR (rRT-PCR) is widely used for SARS-CoV-2 detection but may be limited by the continuous evolution of the virus. However, the sensitivity of Chinese commercial rRT-PCR kits to critical SARS-CoV-2 variants remains unknown. In this study, contrived MS2 virus-like particles were used as reference materials to evaluate the analytical sensitivity of Daan, BioGerm, EasyDiagnosis, Liferiver, and Sansure kits when detecting six important variants (Alpha, Beta, Gamma, Delta, Omicron, and Fin-796H). The Beta and Delta variants adversely affected the analytical sensitivity of the BioGerm ORF1ab gene assay (9.52% versus 42.96%, P = 0.014, and 14.29% versus 42.96%, P = 0.040, respectively), whereas the N gene assay completely failed in terms of the Fin-796H variant. The Gamma and Fin-796H variants impeded the PCR amplification efficiency for the Sansure ORF1ab gene assay (33.33% versus 66.67%, P = 0.031, and 66.67% versus 95.24%, P = 0.040, respectively), and the Delta variant compromised the E gene assay (52.38% versus 85.71%, P = 0.019). The Alpha and Omicron variants had no significant effect on the kits. This study highlights the necessity of identifying the potential effect of viral mutations on the efficacy and sensitivity of clinical detection assays. It can also provide helpful insights regarding the development and optimization of diagnostic assays and aid the strategic management of the ongoing pandemic.

5.
World J Clin Cases ; 10(7): 2253-2260, 2022 Mar 06.
Article in English | MEDLINE | ID: covidwho-1737393

ABSTRACT

BACKGROUND: Plexiform fibromyxoma (PF) is a rare mesenchymal tumor, with limited case reports worldwide. Common clinical symptoms are abdominal discomfort and bleeding signs, which frequently present slow-onset in reported cases. Herein, we report a case of gastric PF presenting as acute onset and with pyemia accom-panying tumor rupture. We resected the tumor as well as the distal gastric, bulbus duodeni and gallbladder for treatment in emergency surgery. Notably, before the onset of the disease, the patient received coronavirus disease 2019 (COVID-19) vaccines. CASE SUMMARY: A 26-year-old man was admitted to our hospital, due to abdominal pain and fever after having received COVID-19 vaccines. Laboratory examination indicated severe sepsis. Computed tomography scan revealed a large mass in the abdomen. Deformation of the gastrointestinal tract was seen during gastroscopy. After failure of anti-infective treatment and symptoms of shock developed, he received an emergency surgery. We found a huge and partly ruptured mass, with thick purulence. Microscopically, the mass was composed of spindle cells with clarified cytoplasm, accompanied by myxoid stroma and arborizing blood vessels. Immunohistochemistry showed the tumor cells as positive for smooth muscle actin and succinate dehydrogenase subunit B but negative for DOG-1 and CD117. Finally, the patient was diagnosed with gastric PF and discharged from the hospital. CONCLUSION: Gastric PF manifesting as tumor rupture combined with pyemia is rare. Timely surgery is critical for optimal prognosis.

6.
Pharmaceutics ; 14(3)2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1737008

ABSTRACT

In recent years, the use of messenger RNA (mRNA) in the fields of gene therapy, immunotherapy, and stem cell biomedicine has received extensive attention. With the development of scientific technology, mRNA applications for tumor treatment have matured. Since the SARS-CoV-2 infection outbreak in 2019, the development of engineered mRNA and mRNA vaccines has accelerated rapidly. mRNA is easy to produce, scalable, modifiable, and not integrated into the host genome, showing tremendous potential for cancer gene therapy and immunotherapy when used in combination with traditional strategies. The core mechanism of mRNA therapy is vehicle-based delivery of in vitro transcribed mRNA (IVT mRNA), which is large, negatively charged, and easily degradable, into the cytoplasm and subsequent expression of the corresponding proteins. However, effectively delivering mRNA into cells and successfully activating the immune response are the keys to the clinical transformation of mRNA therapy. In this review, we focus on nonviral nanodelivery systems of mRNA vaccines used for cancer gene therapy and immunotherapy.

7.
Int J Environ Res Public Health ; 19(5)2022 02 22.
Article in English | MEDLINE | ID: covidwho-1736889

ABSTRACT

Mental health problems are a leading cause of disability in both developed and developing countries, and the consequences of mental health disorders for individuals, families, and society as a whole could be severe and costly. To supplement relevant research and provide insightful policy suggestions to families, government and societies, this study investigates the nexus between natural disasters and mental health for middle-aged and older adults in rural China. Based on data of 8721 observations from the 2014 China Family Panel Studies, we estimate the effects of natural disasters on mental health using ordinary least squares and propensity score matching. Our findings suggest that natural disasters have a significant negative effect on middle-aged and older adults' mental health in the case of rural China. This effect is heterogeneous depending on individuals' education level and their agricultural production status. Finally, individuals' happiness and life satisfaction are shown to be the potential mechanism through which the effect of natural disasters on mental health operates.


Subject(s)
Mental Disorders , Natural Disasters , Aged , China , Cross-Sectional Studies , Humans , Mental Disorders/epidemiology , Mental Disorders/psychology , Mental Health , Middle Aged
8.
iScience ; 25(4): 104043, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1734555

ABSTRACT

With the rapid emergence and spread of SARS-CoV-2 variants, development of vaccines with broad and potent protectivity has become a global priority. Here, we designed a lipid nanoparticle-encapsulated, nucleoside-unmodified mRNA (mRNA-LNP) vaccine encoding the trimerized receptor-binding domain (RBD trimer) and showed its robust capability in inducing broad and protective immune responses against wild-type and major variants of concern (VOCs) in the mouse model of SARS-CoV-2 infection. The protectivity was correlated with RBD-specific B cell responses especially the long-lived plasma B cells in bone marrow, strong ability in triggering BCR clustering, and downstream signaling. Monoclonal antibodies isolated from vaccinated animals demonstrated broad and potent neutralizing activity against VOCs tested. Structure analysis of one representative antibody identified a novel epitope with a high degree of conservation among different variants. Collectively, these results demonstrate that the RBD trimer mRNA vaccine serves as a promising vaccine candidate against SARS-CoV-2 variants and beyond.

9.
Chin Med Sci J ; 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1732612

ABSTRACT

Mother-to-child transmission (MTCT) of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries. In 2007, WHO launched the global elimination of MTCT (EMTCT) of syphilis. Given the high burden of congenital syphilis, China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis. The congenital syphilis incidence rate per 100 000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019. However, due to the global pandemic of COVID-19, the current measures for eliminating MTCT of syphilis are great challenged. In this article, we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years, point out that we have made remarkable achievements due to the national health policy support and strong leadership of the government. In the context of COVID-19 pandemics, strengthening emergency response to the regional outbreaks of COVID-19 and adopting safe, rapid, early and high-quality clinical care to ensure that 100% of pregnant women receive prenatal syphilis testing services, ensuring the availability of Benzathine penicillin for the treatment, and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are key measures to determine the effect of MTCT of syphilis. Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.

10.
Nucleic Acids Res ; 50(5): 2509-2521, 2022 03 21.
Article in English | MEDLINE | ID: covidwho-1722548

ABSTRACT

Upon SARS-CoV-2 infection, viral intermediates specifically activate the IFN response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to viral A-to-I RNA editing. Here, we developed an RNA virus-specific editing identification pipeline, surveyed 7622 RNA-seq data from diverse types of samples infected with SARS-CoV-2, and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2. We found that A-to-I editing was dynamically regulated, varied between tissue and cell types, and was correlated with the intensity of innate immune response. On average, 91 editing events were deposited at viral dsRNA intermediates per sample. Moreover, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. Finally, we provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans during the epidemic. Our study highlights the ability of SARS-CoV-2 to hijack components of the host antiviral machinery to edit its genome and fuel its evolution, and also provides a framework and resource for studying viral RNA editing.


Subject(s)
COVID-19/immunology , Immunity, Innate/immunology , RNA Editing/immunology , SARS-CoV-2/immunology , Adenosine Deaminase/genetics , Adenosine Deaminase/immunology , Adenosine Deaminase/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Base Sequence , Binding Sites/genetics , COVID-19/genetics , COVID-19/virology , Evolution, Molecular , Gene Expression/immunology , Humans , Immunity, Innate/genetics , Interferon-Induced Helicase, IFIH1/genetics , Interferon-Induced Helicase, IFIH1/immunology , Interferon-Induced Helicase, IFIH1/metabolism , Mutation , Protein Binding , RNA Editing/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , RNA-Binding Proteins/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Sequence Homology, Nucleic Acid , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307719

ABSTRACT

During coronavirus disease 2019 (COVID-19) pandemic, medical resources in every country is in shortage. Efficacious indicators of discriminating severe illness and predicting outcome is in urgent need. We collected data and clinical records from 79 COVID-19 patients admitted between January 12, 2020 and February 21, 2020 at Wuhan Union hospital, China. Spearman’s correlation analysis, receiver operating characteristic (ROC) curve, logistic regression model, and Kaplan-Meier survival curves were employed in the analysis. Of 79 patients enrolled, 2 died in hospital, 8 were transferred to other hospitals, and 69 were discharged. Patients with elevated ferritin levels (> 200 ng/mL) had a higher incidence of severity illness when compared with those with normal ferritin levels (≤ 200 ng/mL) (50.0% vs 2.9%). In addition, severity illness manifested significantly higher level of ferritin as compared with non-severe ones (median 921.3 vs 130.7 ng/mL, p < 0.001). Furthermore, ferritin could effectively discriminate severity and non-severity, with an area under the ROC curve (AUC) reaching 0.873 (sensitivity 96%, specificity 70%), larger than that of age (0.697), C-reactive protein (0.730) and lymphocytes% (0.717). Combined model incorporating multivariate revealed a similar manner with ferritin alone (p = 0.981). Furthermore, elevated ferritin group showed longer viral clearance time (median 16 vs 6 days, p < 0.001) and in-hospital length (median 18 vs 10 days, p < 0.001). Our results suggest that ferritin could act as a simple and efficacious complementary tool to identify severe COVID-19 patients at early stage and predict their outcome. This indicator would provide guidance for subsequent clinical practice, alleviate the medical stress and reduce the mortality.

12.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326154

ABSTRACT

While we pay attention to the latest advances in clinical natural language processing (NLP), we can notice some resistance in the clinical and translational research community to adopt NLP models due to limited transparency, interpretability, and usability. In this study, we proposed an open natural language processing development framework. We evaluated it through the implementation of NLP algorithms for the National COVID Cohort Collaborative (N3C). Based on the interests in information extraction from COVID-19 related clinical notes, our work includes 1) an open data annotation process using COVID-19 signs and symptoms as the use case, 2) a community-driven ruleset composing platform, and 3) a synthetic text data generation workflow to generate texts for information extraction tasks without involving human subjects. The corpora were derived from texts from three different institutions (Mayo Clinic, University of Kentucky, University of Minnesota). The gold standard annotations were tested with a single institution's (Mayo) ruleset. This resulted in performances of 0.876, 0.706, and 0.694 in F-scores for Mayo, Minnesota, and Kentucky test datasets, respectively. The study as a consortium effort of the N3C NLP subgroup demonstrates the feasibility of creating a federated NLP algorithm development and benchmarking platform to enhance multi-institution clinical NLP study and adoption. Although we use COVID-19 as a use case in this effort, our framework is general enough to be applied to other domains of interest in clinical NLP.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325114

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide. As of October 27 th , 2020, the number of worldwide laboratory-confirmed cases had reached 43,340,710, with 1,157,496 deaths. We sought to analyze the clinical characteristics, laboratory findings and therapy for a set of COVID-19 cases. Methods: : For this retrospective study, we extracted data for 134 patients with laboratory-confirmed COVID-19 at our hospital from January 16 th to April 24 th , 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until May 1 st , 2020. Results: : An outcome of death or severe COVID-19 was more likely to occur with coinfection and severe underlying diseases. Age above 60 years old, male sex and symptoms such as fever, cough, chest tightness, headaches and fatigue were also related to severe COVID-19 and an outcome of death. In addition, high temperature, high blood leukocyte and neutrophil counts, C-reactive protein and D-dimer levels, and alanine aminotransferase, aspartate aminotransferase, α-hydroxybutyrate dehydrogenase, lactate dehydrogenase and creatine kinase activities were related to severe COVID-19 and an outcome of death, as was a low lymphocyte count. The administration of gamma globulin appeared to be helpful for reducing mortality in patients with severe COVID-19;however, as the P value was greater than 0.05 (P=0.180), studies of the same conditions with larger samples are needed. Conclusion: Multiple factors are related to severe COVID-19 and an outcome of death. The administration of gamma globulin seemed to be helpful for reducing mortality in severe cases. More related studies are needed in the future. Clinical trial registration Not applicable

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325113

ABSTRACT

Background: : As everyone knows, the pandemic COVID-19 is spreading in the whole world. The number of laboratory-confirmed cases reached 28,637,211 and that of the death cases was 917,404 in the world as of September 13 th , 2020. We sought to analyse the clinical characteristics, laboratory findings and therapy of some cases with COVID-19. Methods: : In this retrospective study, we extracted the data on 134 patients with laboratory-confirmed COVID-19 in Wuhan Xinzhou District People's Hospital from January 16 th to April 24 th , 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until May 1 th , 2020. Results: : Co-infection and severe underlying diseases made it easier for a case with COVID-19 to develop to be a severe one or reach an outcome of death. Age above 60 years old, male and symptoms such as fever, cough, chest tightness, headaches and fatigue were related to severe COVID-19 and an outcome of death. In addition, higher temperature, blood leukocyte count, neutrophil count, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α -hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were also related to severe COVID-19 and an outcome of death, and so was lower lymphocyte count. Administration of gamma globulin seemed helpful for reducing the mortality of patients with severe COVID-19, however the P value was greater than 0.05 (P=0.180), which mean under the same condition, studies of larger samples are needed in the future. Conclusion: Multiple factors were related to severe COVID-19 and an outcome of death. Administration of gamma globulin seemed helpful for reducing the mortality of severe cases. More related studies are needed in the future.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324424

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease (COVID-19), recently emerged and led to a global pandemic with enormous consequent losses to global health and economies. To date, more than 30 million cases have been reported globally and have affected almost every with varying degrees. Meteorological and non-meteorological factors such as temperature, relative humidity, atmospheric pressure, population density, and latitude, are considered critical in virus transmission. To explore the correlation of environmental factors with the transmission of SARS-CoV-2 based on parameters including infection rate, effective reproduction number, and compound growth rate, we analyzed data of confirmed cases from 487 counties in the United States. We found a small impact of temperature and humidity on virus transmission, but observed a considerable positive influence of atmospheric pressure and population density on virus transmission. Geographic areas and seasons (autumn and winter), with exposure to higher atmospheric pressure, are more likely at higher risk of an outbreak. Social distancing and other measures could be effective strategies to combat COVID-19 outbreaks in densely populated areas. Additional studies are needed to explore the mechanisms underlying the relationship between meteorological parameters and transmission of SARS-CoV-2.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321467

ABSTRACT

Mice are not susceptible to wildtype SARS-CoV-2 infection. Emerging SARS-CoV-2 variants including B.1.1.7, B.1.351, P.1, and P.3 contain mutations in spike, which have been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that they may have evolved to expand species tropism to rodents. Here, we investigated the capacity of B.1.1.7 and other emerging SARS-CoV-2 variants in infecting mouse (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Our results show that B.1.1.7 and P.3, but not B.1 or wildtype SARS-CoV-2, can utilize mouse and rat ACE2 for virus entry in vitro. High infectious virus titers, abundant viral antigen expression, and pathological changes are detected in the nasal turbinate and lung of B.1.1.7-inocluated mice and rats. Together, these results reveal that the current predominant circulating SARS-CoV-2 variant, B.1.1.7, has gained the capability to expand species tropism to rodents.

17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315510

ABSTRACT

The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. We used retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In several instances, the software utilizes C–H functionalization logic, and one route to umifenovir employs functionalization of six C–H bonds. The general strategy we apply can be used to identify distinct starting materials, and relieve stress on existing supply chains.

18.
Sci China Chem ; : 1-11, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1669939

ABSTRACT

Outbreaks of both influenza virus and the novel coronavirus SARS-CoV-2 are serious threats to human health and life. It is very important to establish a rapid, accurate test with large-scale detection potential to prevent the further spread of the epidemic. An optimized RPA-Cas12a-based platform combined with digital microfluidics (DMF), the RCD platform, was established to achieve the automated, rapid detection of influenza viruses and SARS-CoV-2. The probe in the RPA-Cas12a system was optimized to produce maximal fluorescence to increase the amplification signal. The reaction droplets in the platform were all at the microliter level and the detection could be accomplished within 30 min due to the effective mixing of droplets by digital microfluidic technology. The whole process from amplification to recognition is completed in the chip, which reduces the risk of aerosol contamination. One chip can contain multiple detection reaction areas, offering the potential for customized detection. The RCD platform demonstrated a high level of sensitivity, specificity (no false positives or negatives), speed (≤30 min), automation and multiplexing. We also used the RCD platform to detect nucleic acids from influenza patients and COVID-19 patients. The results were consistent with the findings of qPCR. The RCD platform is a one-step, rapid, highly sensitive and specific method with the advantages of digital microfluidic technology, which circumvents the shortcomings of manual operation. The development of the RCD platform provides potential for the isothermal automatic detection of nucleic acids during epidemics. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11426-021-1169-1.

19.
Bioengineered ; 13(2): 2486-2497, 2022 02.
Article in English | MEDLINE | ID: covidwho-1625949

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can target cardiomyocytes (CMs) to directly invade the heart resulting in high mortality. This study aims to explore the biological characteristics of SARS-CoV-2 infected myocardium based on omics by collecting transcriptome data and analyzing them with a series of bioinformatics tools. Totally, 86 differentially expressed genes (DEGs) were discovered in SARS-CoV-2 infected CMs, and 15 miRNAs were discovered to target 60 genes. Functional enrichment analysis indicated that these DEGs were mainly enriched in the inflammatory signaling pathway. After the protein-protein interaction (PPI) network was constructed, several genes including CCL2 and CXCL8 were regarded as the hub genes. SRC inhibitor saracatinib was predicted to potentially act against the cardiac dysfunction induced by SARS-CoV-2. Among the 86 DEGs, 28 were validated to be dysregulated in SARS-CoV-2 infected hearts. Gene Set Enrichment Analysis (GSEA) analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that malaria, IL-17 signaling pathway, and complement and coagulation cascades were significantly enriched. Immune infiltration analysis indicated that 'naive B cells' was significantly increased in the SARS-CoV-2 infected heart. The above results may help to improve the prognosis of patients with COVID-19.


Subject(s)
COVID-19/immunology , COVID-19/virology , Heart/physiopathology , Heart/virology , Myocardium/pathology , SARS-CoV-2 , Blood Coagulation , Chemokine CCL2/biosynthesis , Complement System Proteins , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Viral , Genome, Human , Humans , Inflammation , Interleukin-17/blood , Interleukin-8/biosynthesis , MicroRNAs/metabolism , Prognosis , Protein Interaction Mapping , Signal Transduction
20.
Nat Commun ; 12(1): 7327, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1585856

ABSTRACT

The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. Here, we utilize retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In one route to umifenovir the software invokes conversion of six C-H bonds into C-C bonds or functional groups. The strategy we apply of excluding known starting materials from search results can be used to identify distinct starting materials, for instance to relieve stress on existing supply chains.


Subject(s)
Antiviral Agents/chemistry , COVID-19/drug therapy , Indoles/chemistry , Software , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Drug Repositioning , Humans , Indoles/therapeutic use , SARS-CoV-2/drug effects
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