Ongoing positive selection drives the evolution of SARS-CoV-2 genomes.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively through world populations since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30, 2021, we demonstrate with population genetic evidence that during the course of SARS-CoV-2 pandemic in humans, (i) SARS-CoV-2 genomes are overall conserved under purifying selection, especially for the 14 genes related to viral RNA replication, transcription, and assembly; (ii) Ongoing positive selection is actively driving the evolution of 6 genes (e.g., S, ORF3a, and N) that play critical roles in molecular processes involving pathogen-host interactions, including viral invasion into and egress from host cells, viral inhibition, or evasion of host immune response, possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution. According to an established haplotype phylogenetic relationship of 138 viral clusters, a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters, of which multiple mutations potentially conferring alterations in viral transmissibility, pathogenicity, and virulence of SARS-CoV-2 are highlighted, warranting attentions.

Universal two-dimensional labelled probe-mediated melting curve analysis based on multiplex PCR for rapid typing of Plasmodium in a single closed tube.

Currently, malaria is still one of the major public health problems commonly caused by the four Plasmodium species. The similar symptoms of malaria and the COVID-19 epidemic of fever or fatigue lead to frequent misdiagnosis. The disadvantages of existing detection methods, such as time-consuming, costly, complicated operation, need for experienced technicians, and indistinguishable typing, lead to difficulties in meeting the clinical requirements of rapid, easy, and accurate typing of common Plasmodium species. In this study, we developed and optimized a universal two-dimensional labelled probe-mediated melting curve analysis (UP-MCA) assay based on multiplex and asymmetric PCR for rapid and accurate typing of five Plasmodium species, including novel human Plasmodium, Plasmodium knowlesi (Pk), in a single closed tube following genome extraction. The assay showed a limit of detection (LOD) of 10 copies per reaction and could accurately distinguish Plasmodium species from intra-plasmodium and other pathogens. Additionally, we proposed and validated different methods of fluorescence quenching and tag design for probes that are suitable for UP-MCA assays. Moreover, the clinical performance of the Plasmodium UP-MCA assay using a base-quenched universal probe was evaluated using 226 samples and showed a sensitivity of 100% (164/164) and specificity of 100% (62/62) at a 99% confidence interval, with the microscopy method as the gold standard. In summary, the UP-MCA assay showed excellent sensitivity, specificity, and accuracy for genotyping Plasmodium species spp. Additionally, it facilitates convenient and rapid Plasmodium detection in routine clinical practice and has great potential for clinical translation.

Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice.

With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after aerosolization and display not only pan-SARS-CoV-2 but also varied pan-sarbecovirus activities. Through respiratory administration to mice, monovalent and decameric R14 significantly reduce the lung viral RNAs at low dose and display potent pre- and post-exposure protection. Furthermore, structural studies reveal the neutralizing mechanisms of R14 and S43 and the multiple inhibition effects that the multivalent derivatives exert. Our work demonstrates promising convenient drug candidates via respiratory administration against SARS-CoV-2 infection, which can contribute to containing the COVID-19 pandemic.

Mental health professionals views and the impact of COVID-19 pandemic on implementing digital mental health in China: A nationwide survey study.

Background: Using digital health technologies (DHTs) to deliver and augment healthcare is an innovative way to solve common challenges that the mental healthcare setting faces. Despite China's rapid development of DHT, a comprehensive understanding of staff views of DHTs is lacking, which limited the evidence to support implementation strategies. In the current study, we aim to: (i) investigate staff attitudes towards digital technology for mental health problems in China; (ii) explore staff's views on the facilitators and barriers regarding uptake and adoption of digital technology in mental health services in China; and (iii) understand how the COVID-19 pandemic has changed staff views on digital mental health. Methods: An online survey was conducted to explore staff attitudes towards implementing DHTs in China. Descriptive statistics were conducted to summarise quantitative data. Free-text data were analysed using qualitative content analysis. Results: 1270 mental health professionals completed the survey. Respondents reported low levels of knowledge of DHTs and moderate levels of accessibility of DHTs in their hospitals. Respondents expressed positive attitudes towards DHTs and demonstrated moderate levels of perceived feasibility and acceptability of implementing DHTs in clinical services. As expected, respondents reported that the COVID-19 pandemic caused significant impacts on their clinical services, and almost all respondents deemed DHTs useful for services provision during the pandemic and were willing to apply such technologies in clinical services after the pandemic. Conclusions: Despite the Chinese mental health staff expressed positive attitudes towards implementing DHTs in clinical practice, most of the staff lacked sufficient knowledge to provide such services. These findings highlight the need to develop implementation strategies such as training programmes and dissemination of research evidence to support the translation of research.

Design and production of environmentally degradable quaternary ammonium salts

Quaternary ammonium compounds (QACs) are a class of cationic surfactants routinely used for the disinfection of industries, institutions and households, and have seen a sharp increase in use during the COVID-19 pandemic. However, current commercial QACs consist of only stable chemical bonds such as C-N, C-C, and C-H, which makes their natural degradation rather difficult. Recent studies suggest that emerging negative environmental impacts, such as systemic antibiotics resistance and toxicity to living organisms, are directly associated with prolonged exposure to QACs. Here we report a new class of QAC which contains relatively volatile chemical functional groups such as ester and thioether bonds. Degradation kinetics in aqueous solutions suggests that the stability of these QACs depends not only on their intrinsic hydrophobicity but also on external environmental factors such as pH, temperature and ion presence. The microbicidal effects of QACs containing carbon chains with various lengths were also tested, one of which, named "Ephemora", is highly active against a broad spectrum of microbes including fungi, bacteria and viruses, for instance, methicillin-resistant Staphylococcus aureus (MRSA). The easy synthesis and purification of Ephemora starting from inexpensive commercially available reagents, together with its excellent antimicrobial activity and ability to degrade in natural waters over time, make its large-scale commercial production possible.

Digital mental health in China: a systematic review.

Mental health problems are highly prevalent in China; however, China's mental health services lack resources to deliver high-quality care to people in need. Digital mental health is a promising solution to this short-fall in view of the population's digital literacy. In this review, we aim to: (i) investigate the effectiveness, acceptability, usability, and safety of digital health technologies (DHTs) for people with mental health problems in China; (ii) critically appraise the literature; and (iii) make recommendations for future research directions. The databases MEDLINE, PsycINFO, EMBASE, Web of Science, CNKI, WANFANG, and VIP were systemically searched for English and Chinese language articles evaluating DHTs for people with mental health problems in mainland China. Eligible studies were systematically reviewed. The heterogeneity of studies included precluded a meta-analysis. In total, 39 articles were retrieved, reporting on 32 DHTs for various mental health problems. Compared with the digital mental health field in the West, the Chinese studies targeted schizophrenia and substance use disorder more often and investigated social anxiety mediated by shame and culturally specific variants, DHTs were rarely developed in a co-production approach, and methodology quality was less rigorous. To our knowledge, this is the first systematic review focused on digital mental health in the Chinese context including studies published in both English and the Chinese language. DHTs were acceptable and usable among Chinese people with mental health problems in general, similar to findings from the West. Due to heterogeneity across studies and a paucity of robust control trial research, conclusions about the efficacy of DHTs are lacking.

Design and production of environmentally degradable quaternary ammonium salts (Electronic supplementary information (ESI) available: Synthesis, characterization, 1H NMR, spectroscopic data and other materials. See DOI: 10.1039/d1gc01525g)

Quaternary ammonium compounds (QACs) are a class of cationic surfactants routinely used for the disinfection of industries, institutions and households, and have seen a sharp increase in use during the COVID-19 pandemic. However, current commercial QACs consist of only stable chemical bonds such as C–N, C–C, and C–H, which makes their natural degradation rather difficult. Recent studies suggest that emerging negative environmental impacts, such as systemic antibiotics resistance and toxicity to living organisms, are directly associated with prolonged exposure to QACs. Here we report a new class of QAC which contains relatively volatile chemical functional groups such as ester and thioether bonds. Degradation kinetics in aqueous solutions suggests that the stability of these QACs depends not only on their intrinsic hydrophobicity but also on external environmental factors such as pH, temperature and ion presence. The microbicidal effects of QACs containing carbon chains with various lengths were also tested, one of which, named “Ephemora”, is highly active against a broad spectrum of microbes including fungi, bacteria and viruses, for instance, methicillin-resistant Staphylococcus aureus (MRSA). The easy synthesis and purification of Ephemora starting from inexpensive commercially available reagents, together with its excellent antimicrobial activity and ability to degrade in natural waters over time, make its large-scale commercial production possible.