Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge.

Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.

Toxicity Evaluation and Effect-Based Identification of Chlorine Disinfection Products of the Anti-COVID-19 Drug Chloroquine Phosphate.

Antiviral transformation products (TPs) generated during wastewater treatment are an environmental concern, as their discharge, in considerable amounts, into natural waters during a pandemic can pose possible risks to the aquatic environment. Identification of the hazardous TPs generated from antivirals during wastewater treatment is important. Herein, chloroquine phosphate (CQP), which was widely used during the coronavirus disease-19 (COVID-19) pandemic, was selected for research. We investigated the TPs generated from CQP during water chlorination. Zebrafish (Danio rerio) embryos were used to assess the developmental toxicity of CQP after water chlorination, and hazardous TPs were estimated using effect-directed analysis (EDA). Principal component analysis revealed that the developmental toxicity induced by chlorinated samples could be relevant to the formation of some halogenated TPs. Fractionation of the hazardous chlorinated sample, along with the bioassay and chemical analysis, identified halogenated TP387 as the main hazardous TP contributing to the developmental toxicity induced by chlorinated samples. TP387 could also be formed in real wastewater during chlorination in environmentally relevant conditions. This study provides a scientific basis for the further assessment of environmental risks of CQP after water chlorination and describes a method for identifying unknown hazardous TPs generated from pharmaceuticals during wastewater treatment.

Engineered soluble ACE2 receptor: Responding to change with change.

SARS coronavirus 2 (SARS-CoV-2) invades the human body by binding to major receptors such as ACE2 via its S-spike protein, so the interaction of receptor-binding sites has been a hot topic in the development of coronavirus drugs. At present, the clinical progress in monoclonal antibody therapy that occurred early in the pandemic is gradually showing signs of slowing. While recombinant soluble ACE2, as an alternative therapy, has been modified by many engineering methods, both the safety and functional aspects are approaching maturity, and this therapy shows great potential for broadly neutralizing coronaviruses, but its progress in clinical development remains stalled. Therefore, there are still several key problems to be considered and solved for recombinant soluble ACE2 to be approved as a clinical treatment as soon as possible.

Aptamers dimerization inspired biomimetic clamp assay towards impedimetric SARS-CoV-2 antigen detection.

Antigen-detecting rapid diagnostic testing (Ag-RDT) has contributed to containing the spread of SARS-CoV-2 variants of concern (VOCs). In this study, we proposed a biomimetic clamp assay for impedimetric SARS-CoV-2 nucleocapsid protein (Np) detection. The DNA biomimetic clamp (DNA-BC) is formed by a pair of Np aptamers connected via a T20 spacer. The 5'- terminal of the DNA-BC is phosphate-modified and then anchored on the surface of the screen-printed gold electrode, which has been pre-coated with Au@UiO-66-NH2. The integrated DNA-material sensing biochip is fabricated through the strong Zr-O-P bonds to form a clamp-type impedimetric aptasensor. It is demonstrated that the aptasensor could achieve Np detection in one step within 11 min and shows pronounced sensitivity with a detection limit of 0.31 pg mL-1. Above all, the aptasensor displays great specificity and stability under physiological conditions as well as various water environments. It is a potentially promising strategy to exploit reliable Ag-RDT products to confront the ongoing epidemic.

Engineered soluble ACE2 receptor: Responding to change with change

SARS coronavirus 2 (SARS-CoV-2) invades the human body by binding to major receptors such as ACE2 via its S-spike protein, so the interaction of receptor-binding sites has been a hot topic in the development of coronavirus drugs. At present, the clinical progress in monoclonal antibody therapy that occurred early in the pandemic is gradually showing signs of slowing. While recombinant soluble ACE2, as an alternative therapy, has been modified by many engineering methods, both the safety and functional aspects are approaching maturity, and this therapy shows great potential for broadly neutralizing coronaviruses, but its progress in clinical development remains stalled. Therefore, there are still several key problems to be considered and solved for recombinant soluble ACE2 to be approved as a clinical treatment as soon as possible.

Mental health and psychosocial problems among laboratory technicians in response to the COVID-19 pandemic in Hebei, China.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

Key Predictive Factors in the Mental Health of Chinese University Students at Home and Abroad.

The prevalence of reported mental health problems among university students has increased at alarming rates in recent years. While various negative life events (from personal events such as relationship breakdowns to more global events such as COVID-19 [SARS-CoV-2] pandemic) have been found to be important predictors of poor mental health in this population, some individuals have been found robustly to fare better than others in confronting such events. Identifying factors that predict these individuals' mental health, along with the specific coping strategies they utilize may have significant practical implications when confronted by adverse events such as COVID-19. This study investigated relationships between the impact of the COVID-19 pandemic on 828 (453 females, 374 males, and one "Other") Chinese university students' mental health, and their internal strengths, personality characteristics, and demographic profiles. We also investigated whether students' use of specific coping strategies mediated these relationships. Stepwise multiple regression analyses (MRAs) and a path analysis revealed that students who resided in their home country, had higher levels of internal strengths, a lower level of neuroticism and a higher level of agreeableness and reported fewer negative mental health changes than did other respondents during COVID-19 in the second half of 2020. Self-regulation and withdrawal coping strategies were both important mediators of these relationships. These findings have important implications for universities in identifying and assisting students in the face of adverse events such as COVID-19.

Validation of the Mental Health Changes Indicators Scale against Rasch measurement theory

The Mental Health Changes Indicators Scale (MHCIS) is a brief instrument designed to assess changes in an individual's mental health that occur in response to a specific life event. Although adequate psychometric properties have been demonstrated for this instrument based on classical test theory, the MHCIS has not yet been validated against Rasch measurement theory (RMT). We applied RMT to examine the psychometric properties of the MHCIS using data from 807 Chinese university students. The nominated life event in this study was the COVID-19 pandemic. Despite modest violations of unidimensionality and misfit to the Rasch model, in general, the results supported the validity of the 10-item MHCIS. We recommend further exploration of the generalizability of these results in other populations and across a range of potentially adverse life events.

Artificial intelligence model on chest imaging to diagnose COVID-19 and other pneumonias: A systematic review and meta-analysis.

Objectives: When diagnosing Coronavirus disease 2019(COVID-19), radiologists cannot make an accurate judgments because the image characteristics of COVID-19 and other pneumonia are similar. As machine learning advances, artificial intelligence(AI) models show promise in diagnosing COVID-19 and other pneumonias. We performed a systematic review and meta-analysis to assess the diagnostic accuracy and methodological quality of the models. Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase, preprints from medRxiv and bioRxiv to locate studies published before December 2021, with no language restrictions. And a quality assessment (QUADAS-2), Radiomics Quality Score (RQS) tools and CLAIM checklist were used to assess the quality of each study. We used random-effects models to calculate pooled sensitivity and specificity, I2 values to assess heterogeneity, and Deeks' test to assess publication bias. Results: We screened 32 studies from the 2001 retrieved articles for inclusion in the meta-analysis. We included 6737 participants in the test or validation group. The meta-analysis revealed that AI models based on chest imaging distinguishes COVID-19 from other pneumonias: pooled area under the curve (AUC) 0.96 (95 % CI, 0.94-0.98), sensitivity 0.92 (95 % CI, 0.88-0.94), pooled specificity 0.91 (95 % CI, 0.87-0.93). The average RQS score of 13 studies using radiomics was 7.8, accounting for 22 % of the total score. The 19 studies using deep learning methods had an average CLAIM score of 20, slightly less than half (48.24 %) the ideal score of 42.00. Conclusions: The AI model for chest imaging could well diagnose COVID-19 and other pneumonias. However, it has not been implemented as a clinical decision-making tool. Future researchers should pay more attention to the quality of research methodology and further improve the generalizability of the developed predictive models.

Recent advances in applying G-quadruplex for SARS-CoV-2 targeting and diagnosis: A review.

The coronavirus SARS-CoV-2 has caused a health care crisis all over the world since the end of 2019. Although vaccines and neutralizing antibodies have been developed, rapidly emerging variants usually display stronger immune escape ability and can better surpass vaccine protection. Therefore, it is still vital to find proper treatment strategies. To date, antiviral drugs against SARS-CoV-2 have mainly focused on proteases or polymerases. Notably, noncanonical nucleic acid structures called G-quadruplexes (G4s) have been identified in many viruses in recent years, and numerous G4 ligands have been developed. During this pandemic, literature on SARS-CoV-2 G4s is rapidly accumulating. Here, we first summarize the recent progress in the identification of SARS-CoV-2 G4s and their intervention by ligands. We then introduce the potential interacting proteins of SARS-CoV-2 G4s from both the virus and the host that may regulate G4 functions. The innovative strategy to use G4s as a diagnostic tool in SARS-CoV-2 detection is also reviewed. Finally, we discuss some key questions to be addressed in the future.

Optimized Self-Adaptive Power Distribution for Microgrids in a Typical Tourism Water Village of Northern China under COVID-19 Background

This work presents an improved self-adaptive power distribution approach for the microgrid in five modes under different pandemic conditions in a typical tourism water village in Northern China. Differently from the other studies, this work concentrates on satisfying the specific power supply requirements under the COVID-19 background, with the maximum value of the composite index as the object function. Composite index includes not only the economic factors, but also some compulsive factors to ensure the requested power supply of the residents/tourists. The improved particle swarm optimization method which employs the modified weighted factor and the elite strategy is utilized to optimize the power dispatching of the microgrid. Moreover, the impact of the pandemic has been fully considered by comparing the power dispatching before and after the pandemic. The case study in Baiyangdian Region confirms the effectiveness of the proposed method. With this method, the optimal power dispatching is determined under different modes.

Targeting the RNA G-Quadruplex and Protein Interactome for Antiviral Therapy.

In recent years, G-quadruplexes (G4s), types of noncanonical four-stranded nucleic acid structures, have been identified in many viruses that threaten human health, such as HIV and Epstein-Barr virus. In this context, G4 ligands were designed to target the G4 structures, among which some have shown promising antiviral effects. In this Perspective, we first summarize the diversified roles of RNA G4s in different viruses. Next, we introduce small-molecule ligands developed as G4 modulators and highlight their applications in antiviral studies. In addition to G4s, we comprehensively review the medical intervention of G4-interacting proteins from both the virus (N protein, viral-encoded helicases, severe acute respiratory syndrome-unique domain, and Epstein-Barr nuclear antigen 1) and the host (heterogeneous nuclear ribonucleoproteins, RNA helicases, zinc-finger cellular nucelic acid-binding protein, and nucleolin) by inhibitors as an alternative way to disturb the normal functions of G4s. Finally, we discuss the challenges and opportunities in G4-based antiviral therapy.

International Students' Mental Health Amidst COVID-19-A Systematic Review Based on Current Evidence

While the psychological impact of the COVID-19 pandemic has been widely discussed during the past two years, little attention has been given to international students. This study aimed to systematically review all the empirical studies regarding international students' mental health amidst COVID-19. A search of the peer-reviewed papers was conducted using PsycINFO, Google Scholar, ProQuest Psychology, PubMed, Web of Science and ProQuest Public Health on 5 January 2022. Articles were selected based on inclusion and exclusion criteria created. Eighteen studies were finally included in this review. Findings showed that international students experienced various adverse psychological outcomes during COVID-19. Protective and risk factors that have been found to correlate with international students' mental health were reviewed. Four possible avenues for future research, based on the current literature are identified and discussed.

Mental Health Risks for Chinese International Students in Australia: Enduring Problems, Possible Solutions

This paper explores existing evidence on indicators of risk to the mental health status of Chinese students studying in Australian universities prior to the COVID-19 pandemic. Studies published from January 1999 to January 2020 were considered. Findings indicated that Chinese students routinely report increased levels of fear, stress, anxiety, depression and social problems, as well as decreased levels of general well-being, while studying in Australia. Numerous factors may exacerbate the issues confronted by Chinese university students studying in Australia, including language barriers;social, academic and financial difficulties;challenges associated with the different education systems of the two countries;and their own underuse of available mental health services. Recommendations for further practice and research are presented based on these findings.

Anxiety and PTSD Symptoms During the COVID-19 Pandemic in Women With Breast Cancer.

OBJECTIVES: To examine (a) the impact of the COVID-19 pandemic on anxiety and post-traumatic stress disorder (PTSD) symptoms and (b) the impact of socioeconomic factors on COVID-19-related anxiety and PTSD symptoms. SAMPLE & SETTING: Women with early-stage invasive breast cancer who were receiving chemotherapy in western Pennsylvania and eastern Ohio. METHODS & VARIABLES: Baseline study variables included economic hardship, interpersonal relationships, and perceived stress. PTSD and anxiety symptoms were collected in June 2020 (T1) and February 2021 (T2). Group comparisons were made using paired-sample t tests, analysis of variance, and Pearson correlations. RESULTS: There were 88 women at T1 and 64 women at T2. At T1, PTSD symptom scores were significantly associated with less interpersonal support, greater economic hardship, and greater perceived stress. Anxiety scores were associated with perceived stress. At T2, anxiety scores were still associated with perceived stress. However, PTSD symptom scores were no longer associated with interpersonal support, economic hardship, or perceived stress. IMPLICATIONS FOR NURSING: Anxiety and PTSD symptom measurement during a global pandemic is needed to identify vulnerable patients with breast cancer who need targeted support and emergency guidance in nursing practice.

Prolong the flushing and locking interval of TIVAD is feasible in COVID-19: An overview of systematic reviews.

The aim of the overview was to synthesize existing systematic reviews (SRs) of flushing interval for patients who inserted totally implanted venous catheter devices (TIVAD). Regular flushing is indispensable for catheter patency, the recommended flushing interval of TIVAD is 4 weeks, however, there is an argument for prolonging the maintenance interval, which has been proved by many SRs. However, the flushing interval range from 4-week to 3-month. The discrepancy in maintenance period could puzzle health professionals and hinder best practice into the clinic. So, we performed the overview by following the PRISMA statement. The PubMed, Ovid, Wan Fang database, Web of Science, CINAHL, CNKI, EMBASE, Cochrane Library were searched from inception to November 2021. The AMSTAR-2, the PRISMA statement, and ROBIS tool were used to assess SRs' method, report quality, and risk of bias, respectively. Then all results were synthesized, the quality of SRs' results was evaluated with GRADE. Finally, five SRs were included. However, non-randomized and small sample size of original studies result in the limitation of SRs. The evidence grade of conclusions is low, bias of mixed factors in included studies, further large sample sizes, RCTs need to be conducted in the future. Prolonged flushing interval was feasible based on the recent evidence, especially during the COVID-19 pandemic because the overwhelming healthcare system and inconvenience of transportation made maintenance not as easy as it used to be. There is no difference of complication between prolonged flushing interval (⩾4-week) and 4-week period, and it can also reduce healthcare cost with no harm to patients.

Development and Validation of a Coping Strategies Scale for Use in Chinese Contexts.

Individuals' coping strategies have a profound effect on how well they respond to negative life events. Despite this, most coping strategies instruments that are available currently have been developed exclusively in Western contexts. In the present study, a Coping Strategies Scale (CSS) for use with Chinese participants was developed and validated based on responses from 734 Chinese university students (334 male, 399 female, 1 other). Results supported a seven-factor structure for the CSS, which included the dimensions of Withdrawal, Positive Adaptation, Problem-solving, Disengagement, Prosocial Focus, Seeking Emotional Support, and Self-regulation. The results supported the validity of the seven-factor CSS in terms of its content, associated response processes, internal structure, and relationships with other variables. Based on these results, the CSS provides a psychometrically sound instrument for assessing the coping strategies used by Chinese adults in confronting potentially adverse psychological events.

Association of Use of Tourniquets During Total Knee Arthroplasty in the Elderly Patients With Post-operative Pain and Return to Function.

Objective: During total knee arthroplasty (TKA), tourniquet may negatively impact post-operative functional recovery. This study aimed at investigating the effects of tourniquet on pain and return to function. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15th, 2020. Search terms included; total knee arthroplasty, tourniquet, and randomized controlled trial. RCTs evaluating the efficacies of tourniquet during and after operation were selected. Two reviewers independently extracted the data. Effect estimates with 95% CIs were pooled using the random-effects model. Dichotomous data were calculated as relative risks (RR) with 95% confidence intervals (CI). Mean differences (MD) with 95% CI were used to measure the impact of consecutive results. Primary outcomes were the range of motion (ROM) and visual analog scale (VAS) pain scores. Results: Thirty-three RCTs involving a total of 2,393 patients were included in this study. The mean age is 65.58 years old. Compared to no tourniquet group, the use of a tourniquet resulted in suppressed ROM on the 3rd post-operative day [MD, -4.67; (95% CI, -8.00 to -1.35)] and the 1st post-operative month [MD, -3.18; (95% CI, -5.92 to -0.44)]. Pain increased significantly when using tourniquets on the third day after surgery [MD, 0.39; (95% CI, -0.19 to 0.59)]. Moreover, tourniquets can reduce intra-operative blood loss [MD, -127.67; (95% CI, -186.83 to -68.50)], shorter operation time [MD, -3.73; (95% CI, -5.98 to -1.48)], lower transfusion rate [RR, 0.85; (95% CI, 0.73-1.00)], higher superficial wound infection rates RR, 2.43; [(5% CI, 1.04-5.67)] and higher all complication rates [RR, 1.98; (95% CI, 1.22-3.22)]. Conclusion: Moderate certainty evidence shows that the use of a tourniquet was associated with an increased risk of higher superficial wound infection rates and all complication rates. Therefore, the findings did not support the routine use of a tourniquet during TKA.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.