Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation.

In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived N-triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as "covalent warhead" in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.

Microplastics in soils during the COVID-19 pandemic: Sources, migration and transformations, and remediation technologies.

The COVID-19 pandemic has led to a notable upsurge of 5-10 % in global plastic production, which could have potential implications on the soil quality through increased microplastics (MPs) content. The elevated levels of MPs in the soil poses a significant threat to both the environment and human health, hence necessitating the remediation of MPs in the environment. Despite the significant attention given to MPs remediation in aqueous environments, less consideration has been given to MPs remediation in the soil. Consequently, this review highlights the major sources of MPs in the soil, their migration and transformation behaviors during the COVID-19 pandemic, and emphasizes the importance of utilizing remediation technologies such as phytoremediation, thermal treatment, microbial degradation, and photodegradation for MPs in the soil. Furthermore, this review provides a prospective outlook on potential future remediation methods for MPs in the soil. Although the COVID-19 pandemic is nearing its end, the long-term impact of MPs on the soil remains, making this review a valuable reference for the remediation of MPs in the post-pandemic soil.

Knowledge, attitude, and practices on COVID-19 prevention and diagnosis among medical workers in the radiology department: A multicenter cross-sectional study in China.

Objective: The aim of this study was to investigate the knowledge, attitude, and practice (KAP) of medical workers in the radiology department toward the prevention and diagnosis of COVID-19. Methods: This multicenter cross-sectional study was conducted among medical workers in the radiology department of 17 hospitals between March and June 2022. Results: A total of 324 medical workers were enrolled. The mean knowledge scores were 15.3 ± 3.4 (out of 23), attitude scores were 31.1 ± 5.6 (range 8-40), and practice scores were 35.1 ± 4.4 (range 8-40). Positive attitudes (OR = 1.235, 95% CI: 1.162-1.311, P < 0.001) and aged 41-50 years were independently associated with higher practice scores. Those with the better practice were more likely to be older (OR = 2.603, 95% CI: 1.242-5.452, P = 0.011), nurses (OR = 2.274, 95% CI: 1.210-4.272, P = 0.011) and with junior/intermediary/vice-senior title (OR = 2.326, 95% CI: 1.030-5.255, P = 0.042; OR = 2.847, 95% CI: 1.226-6.606, P = 0.015; OR = 4.547, 95% CI: 1.806-11.452, P = 0.001, respectively). Subgroup analysis revealed significant differences in knowledge between technicians and physicians and nurses and between staff working in tertiary hospitals and non-tertiary hospitals. Knowledge is positively correlated with attitude (ß = 0.54, P < 0.001), and attitude is positively correlated with practice (ß = 0.37, P < 0.001). Attitudes significantly mediated the association between knowledge and practice (ß = 0.119, P < 0.001). Conclusion: The radiology medical workers showed moderate knowledge but good attitudes and practices of prevention and diagnosis of COVID-19. Attitudes were found to be positively associated with better practices of prevention and diagnosis of COVID-19. Attitudes significantly mediated the association between knowledge and practice.

Development of a multiplex qRT-PCR assay for the detection of porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus and porcine Deltacoronavirus.

Currently, porcine coronaviruses are prevalent in pigs, and due to the outbreak of COVID-19, porcine coronaviruses have become a research hotspot. porcine epidemic diarrhea virus (PEDV), Transmissible Gastroenteritis Virus (TGEV), and Porcine Deltacoronavirus (PDCoV) mentioned in this study mainly cause diarrhea in pigs. These viruses cause significant economic losses and pose a potential public health threat. In this study, specific primers and probes were designed according to the M gene of PEDV, the S gene of TGEV, and the M gene of PDCoV, respectively, and TaqMan probe-based multiplex real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was developed for the simultaneous detection of PEDV, TGEV, and PDCoV. This method has high sensitivity and specificity, and the detection limit of each virus can reach 2.95 × 100 copies/µl. An assay of 160 clinical samples from pigs with diarrhea showed that the positive rates of PEDV, TGEV, and PDCoV were 38.13, 1.88, and 5.00%; the coinfection rates of PEDV+TGEV, PEDV+PDCoV, TGEV+PDCoV, PEDV+TGEV+PDCoV were 1.25, 1.25, 0, 0.63%, respectively. The positive coincidence rates of the multiplex qRT-PCR and single-reaction qRT-PCR were 100%. This method is of great significance for clinical monitoring of the porcine enteric diarrhea virus and helps reduce the loss of the breeding industry and control the spread of the disease.

eIF3d: A driver of noncanonical cap-dependent translation of specific mRNAs and a trigger of biological/pathological processes.

Eukaryotic initiation factor 3d (eIF3d), a known RNA-binding subunit of the eIF3 complex, is a 66 to 68-kDa protein with an RNA-binding motif and a cap-binding domain. Compared with other eIF3 subunits, eIF3d is relatively understudied. However, recent progress in studying eIF3d has revealed a number of intriguing findings on its role in maintaining eIF3 complex integrity, global protein synthesis, and in biological and pathological processes. It has also been reported that eIF3d has noncanonical functions in regulating translation of a subset of mRNAs by binding to 5'-UTRs or interacting with other proteins independent of the eIF3 complex and additional functions in regulating protein stability. The noncanonical regulation of mRNA translation or protein stability may contribute to the role of eIF3d in biological processes such as metabolic stress adaptation and in disease onset and progression including severe acute respiratory syndrome coronavirus 2 infection, tumorigenesis, and acquired immune deficiency syndrome. In this review, we critically evaluate the recent studies on these aspects of eIF3d and assess prospects in understanding the function of eIF3d in regulating protein synthesis and in biological and pathological processes.

Plasmonic Biosensors with Nanostructure for Healthcare Monitoring and Diseases Diagnosis.

Nanophotonics has been widely utilized in enhanced molecularspectroscopy or mediated chemical reaction, which has major applications in the field of enhancing sensing and enables opportunities in developing healthcare monitoring. This review presents an updated overview of the recent exciting advances of plasmonic biosensors in the healthcare area. Manufacturing, enhancements and applications of plasmonic biosensors are discussed, with particular focus on nanolisted main preparation methods of various nanostructures, such as chemical synthesis, lithography, nanosphere lithography, nanoimprint lithography, etc., and describing their respective advances and challenges from practical applications of plasmon biosensors. Based on these sensing structures, different types of plasmonic biosensors are summarized regarding detecting cancer biomarkers, body fluid, temperature, gas and COVID-19. Last, the existing challenges and prospects of plasmonic biosensors combined with machine learning, mega data analysis and prediction are surveyed.

SARS-CoV-2 BA.2 (Omicron) variant infection in pediatric liver transplanted recipients and cohabitants during 2022 Shanghai outbreak: a prospective cohort.

BACKGROUND: The Omicron variant BA.2 was the dominant variant in the COVID-19 outbreak in Shanghai since March 2022. We aim to investigate the characteristics of SARS-CoV-2 Omicron variant infection in pediatric liver-transplanted recipients. METHODS: We conducted a single-center, prospective, observational, single-arm study. We enrolled pediatric liver-transplanted patients infected with the Omicron variant BA.2 from March 19th to October 1st, 2022 and analyzed their demographic, clinical, laboratory, and outcome data. The management of COVID-19 was conducted according to the 9th trial edition of the Chinese guideline. The immunosuppressive therapy was tailored considering the patients' infection developments and liver functions. RESULTS: Five children were included. The primary diseases included Niemann-Pick disease, propionic acidemia, decompensated cirrhosis, biliary atresia, and Crigler-Najjar syndrome type I. All of the patients were onset with fever before or when getting RNA-positive results at the age of 3 (Range: 1-13) years. The infection duration was 29 (Range: 18-40) days. Three and two children were diagnosed with mild and moderate COVID-19 respectively. Two patients were tested RNA-positive within 14 days after having been tested negative. The immunosuppressants were paused or extenuated in four patients. Eight of all nine cohabitants were injected with at least two doses of inactivated SARS-CoV-2 vaccine. The disease courses were significantly longer than the patients (P < 0.05). CONCLUSIONS: Post-transplant immunosuppression slows down the virus clearance and increases the risk of relapse but does not affect symptom duration or infection severity in pediatric patients. Patients can usually gain a favorable outcome and prognosis by extenuating immunosuppressants.

Effectiveness of inactivated COVID-19 vaccines against mild disease, pneumonia, and severe disease among persons infected with SARS-CoV-2 Omicron variant: Real-world study in Jilin Province, China.

BACKGROUND: : It is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. METHODS: . This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. RESULTS: . A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1029, mild disease: 1858, pneumonia: 108, severe disease: 21) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. CONCLUSION: . The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

New Onset of Severe Plaque Psoriasis Following COVID-19 Vaccination: A Case Report.

A case of new onset of severe plaque psoriasis following COVID-19 vaccination was reported. A 63-year-old woman presented with multiple plaques for 2 months after the second dose of COVID-19 vaccination. Dermatological examination revealed diffuse erythematous papules and plaques on trunk and limbs. Her lesions responded well to the treatment of secukinumab 150 mg per week. In this case, we presented the potential association between COVID-19 vaccination and the onset of psoriasis. It is essential to recognize the possible adverse events as vaccination against COVID-19 continues worldwide.

The clinical characteristics and risk factors for severe COVID-19 in patients with COVID-19 and tuberculosis coinfection.

Background: Under the wave of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variant Omicron epidemic, the number of infectious cases has increased dramatically in Jilin Province, China since March 2022.The clinical features and severity of SARS-CoV-2 Omicron variant infection in tuberculosis (TB) patients are not yet clear. Methods: Data were obtained from 153 patients with the Omicron variant and TB coinfection and 153 non-TB COVID-19 patients who had been hospitalized at Changchun Infectious Disease Hospital from March to June 2022. Results: Among these coinfection patients, 17 patients showed COVID-19-related pneumonia on chest imaging and 11 were diagnosed with severe COVID-19. The median duration of SARS-CoV-2 clearance was 13 days. The negative conversion time was associated with age, COVID-19-related pneumonia and antibody IgG. A higher white blood cell count, a lower lymphocyte percentage, a higher CRP level, and a higher D-dimer level were found in the severe group. Age and increased PCT were individual risk factors for the severity of COVID-19. Compared with the non-TB patients, the coinfection patients had higher severity of COVID-19 and the elder coinfection patients had a longer negative conversion time. Conclusion: This study found an association between age, pneumonia, antibody IgG and RNA negative conversion time in COVID-19 and TB coinfection patients, and age and increased PCT were risk factors for the severity of COVID-19.

Monoclonal antibodies constructed from COVID-19 convalescent memory B cells exhibit potent binding activity to MERS-CoV spike S2 subunit and other human coronaviruses.

Introduction: The Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are two highly contagious coronaviruses causing MERS and COVID-19, respectively, without an effective antiviral drug and a long-lasting vaccine. Approaches for diagnosis, therapeutics, prevention, etc., particularly for SARS-CoV-2 that is continually spreading and evolving, are urgently needed. Our previous study discovered that >60% of sera from convalescent COVID-19 individuals, but <8% from general population, showed binding activity against the MERS-CoV spike protein, indicating that SARS-CoV-2 infection boosted antibodies cross-reactive with MERS-CoV. Methods: To generate antibodies specific to both SARS-CoV-2 and MERS-CoV, here we screened 60 COVID-19 convalescent sera against MERS-CoV spike extracellular domain and S1 and S2 subunits. We constructed and characterized monoclonal antibodies (mAbs) from COVID-19 convalescent memory B cells and examined their binding and neutralizing activities against human coronaviruses. Results and Discussion: Of 60 convalescent serum samples, 34 showed binding activity against MERS-CoV S2, with endpoint titers positively correlated with the titers to SARS-CoV-2 S2. By sorting single memory B cells from COVID-19 convalescents, we constructed 38 mAbs and found that 11 mAbs showed binding activity with MERS-CoV S2, of which 9 mAbs showed potent cross-reactivity with all or a proportion of spike proteins of alphacoronaviruses (229E and NL63) and betacoronaviruses (SARS-CoV-1, SARS-CoV-2, OC43, and HKU1). Moreover, 5 mAbs also showed weak neutralization efficiency against MERS-CoV spike pseudovirus. Epitope analysis revealed that 3 and 8 mAbs bound to linear and conformational epitopes in MERS-CoV S2, respectively. In summary, we have constructed a panel of antibodies with broad-spectrum reactivity against all seven human coronaviruses, thus facilitating the development of diagnosis methods and vaccine design for multiple coronaviruses.

Impact of COVID-19 pandemic on acute pancreatitis presentations, management, and in-hospital outcomes: a single-center, retrospective observational study from the northeast of China.

Background: Since initially detected in late December 2019, the novel coronavirus disease 2019 (COVID-19) outbreak rapidly swept the world, which has profoundly affected healthcare system and clinical practice in the management of gastrointestinal diseases. Objectives: We aimed to evaluate the impact of COVID-19 pandemic on the pattern of hospital admissions and healthcare services for acute pancreatitis (AP). Design: We conducted a retrospective observational cohort study using the anonymized electronic medical records. Methods: This single-center, retrospective observational study from a regional medical center in the northeast of China included all consecutively admitted patients with AP from 23 January to 10 June 2020 (during the COVID-19 outbreak in Harbin), compared with the equivalent period of the previous year, in terms of demographics, clinical characteristics, and in-hospital outcomes. Results: In this article, we observed a reduction in AP admissions after the beginning of COVID-19 outbreak. With the prolonged time from symptom onset to hospitalization [32.0 (22.0-72.0) versus 18.0 (12.0-24.0) h; p < 0.001], a higher proportion of AP patients developed acute renal failure (14.0% versus 7.4%, p = 0.004) and acute necrotic collection (16.5% versus 11.2%; p = 0.038) in the COVID-19 era. The percentage of alcohol etiology significantly decreased after the implementation of social restriction measures (11.5% versus 20.4%; p = 0.002), whereas biliary etiology was numerically more common amidst the COVID-19 era (41.6% versus 32.6%; p = 0.014). No significant differences were found in the rates of intensive care unit admission and mortality between the two groups. Conclusion: This study preliminarily demonstrated the descending trend and delay in hospital presentations for AP during the outbreak of COVID-19. Given that the pandemic may persist for several years, adjustments of medical services according to the varying degrees of local breakouts are imperative to provide appropriate care for AP patients and diminish the risk of viral transmission. Registration: ClincialTrials.gov number ChiCTR2100043350.

Federated Active Learning for Multicenter Collaborative Disease Diagnosis.

Current computer-aided diagnosis system with deep learning method plays an important role in the field of medical imaging. The collaborative diagnosis of diseases by multiple medical institutions has become a popular trend. However, large scale annotations put heavy burdens on medical experts. Furthermore, the centralized learning system has defects in privacy protection and model generalization. To meet these challenges, we propose two federated active learning methods for multicenter collaborative diagnosis of diseases: the Labeling Efficient Federated Active Learning (LEFAL) and the Training Efficient Federated Active Learning (TEFAL). The proposed LEFAL applies a task-agnostic hybrid sampling strategy considering data uncertainty and diversity simultaneously to improve data efficiency. The proposed TEFAL evaluates the client informativeness with a discriminator to improve client efficiency. On the Hyper-Kvasir dataset for gastrointestinal disease diagnosis, with only 65% of labeled data, the LEFAL achieves 95% performance on the segmentation task with whole labeled data. Moreover, on the CC-CCII dataset for COVID-19 diagnosis, with only 50 iterations, the accuracy and F1-score of TEFAL are 0.90 and 0.95, respectively on the classification task. Extensive experimental results demonstrate that the proposed federated active learning methods outperform state-of-the-art methods on segmentation and classification tasks for multicenter collaborative disease diagnosis.

Elevated ubiquitination contributes to protective immunity against severe SARS-CoV-2 infection.

BACKGROUND: The crosstalk between the ubiquitin-proteasome and the immune system plays an important role in the health and pathogenesis of viral infection. However, there have been few studies of ubiquitin activation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We investigated the effect of ubiquitination on SARS-CoV-2 infection and patient prognosis by integrating published coronavirus disease 2019 (COVID-19) multi-transcriptome data and bioinformatics methods. RESULTS: The differential expression of COVID-19 samples revealed changed ubiquitination in most solid and hollow organs, and it was activated in lymphatic and other immune tissues. In addition, in the respiratory system of COVID-19 patients, the immune response was mainly focused on the alveoli, and the expression of ubiquitination reflected increasing immune infiltration. Ubiquitination stratification could significantly differentiate patients' prognosis and inflammation levels through the general transcriptional analysis of the peripheral blood of patients with COVID-19. Moreover, high ubiquitination levels were associated with a favourable prognosis, low inflammatory response, and reduced mechanical ventilation and intensive care unit. Moreover, high ubiquitination promoted a beneficial immune response while inhibiting immune damage. Finally, prognostic stratification and biomarker screening based on ubiquitination traits played an important role in clinical management and drug development. CONCLUSION: Ubiquitination characteristics provides new ideas for clinical intervention and prognostic guidance for COVID-19 patients.

Lymphocyte-C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission.

In this study, we aimed to explore whether lymphocyte-C-reactive protein ratio (LCR) can differentiate disease severity of coronavirus disease 2019 (COVID-19) patients and its value as an assistant screening tool for admission to hospital and intensive care unit (ICU). A total of 184 adult COVID-19 patients from the COVID-19 Treatment Center in Heilongjiang Province at the First Affiliated Hospital of Harbin Medical University between January 2020 and March 2021 were included in this study. Patients were divided into asymptomatic infection group, mild group, moderate group, severe group, and critical group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data including gender, age, comorbidities, severity of COVID-19, white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), red blood cell distribution width (RDW), platelet (PLT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), albumin (ALB), total bilirubin (TB), direct bilirubin (DBIL), indirect bilirubin (IBIL), and D-dimer were obtained and collated from medical records at admission, from which sequential organ failure assessment (SOFA) score and LCR were calculated, and all the above indicators were compared among the groups. Multiple clinical parameters, including LYMPH, CRP, and LCR, showed significant differences among the groups. The related factors to classify COVID-19 patients into moderate, severe, and critical groups included age, number of comorbidities, WBC, LCR, and AST. Among these factors, the number of comorbidities showed the greatest effect, and only WBC and LCR were protective factors. The area under the receiver operating characteristic (ROC) curve of LCR to classify COVID-19 patients into moderate, severe, and critical groups was 0.176. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 1,780.7050 and 84.6% and 66.2%, respectively. The related factors to classify COVID-19 patients into severe and critical groups included the number of comorbidities, PLT, LCR, and SOFA score. Among these factors, SOFA score showed the greatest effect, and LCR was the only protective factor. The area under the ROC curve of LCR to classify COVID-19 patients into severe and critical groups was 0.106. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 571.2200 and 81.3% and 90.0%, respectively. In summary, LCR can differentiate disease severity of COVID-19 patients and serve as a simple and objective assistant screening tool for hospital and ICU admission.