Emerging mRNA technologies: delivery strategies and biomedical applications.

The great success achieved by the two highly-effective messenger RNA (mRNA) vaccines during the COVID-19 pandemic highlights the great potential of mRNA technology. Through the evolution of mRNA technology, chemistry has played an important role from mRNA modification to the synthesis of mRNA delivery platforms, which allows various applications of mRNA to be achieved both in vitro and in vivo. In this tutorial review, we provide a summary and discussion on the significant progress of emerging mRNA technologies, as well as the underlying chemical designs and principles. Various nanoparticle (NP)-based delivery strategies including protein-mRNA complex, lipid-based carriers, polymer-based carriers, and hybrid carriers for the efficient delivery of mRNA molecules are presented. Furthermore, typical mRNA delivery platforms for various biomedical applications (e.g., functional protein expression, vaccines, cancer immunotherapy, and genome editing) are highlighted. Finally, our insights into the challenges and future development towards clinical translation of these mRNA technologies are provided.

The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder.

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

COVID-19 Outbreak Can Change the Job Burnout in Health Care Professionals.

Background: The outbreak of COVID-19 in China was a sudden bio-disaster, which may bring a negative impact on the job burnout of health care professionals (HCPs). Objective: We aim to find out the association factors, especially those closely related to this outbreak, of job burnout in Chinese HCPs. Method: The cross-sectional survey about HCPs' job burnout based on a network platform was conducted in high and low infection regions during the COVID-19 outbreak in China. The demographic characteristics, medical-work-related factors, risk of getting infected due to occupational exposure, and family factors were collected by the self-reported questionnaire. The Chinese version of the Maslach Burnout Inventory (CMBI) and the Trait Coping Style Questionnaire (TCSQ) were employed in this study to evaluate the job burnout and coping style, respectively. Furthermore, statistical analysis was done to find out the associated factors of job burnout. Results: We collected 880 complete questionnaires from doctors and nurses from February 9, 2020 to February 11, 2020. In this study, the positive rates of three dimensions of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) and overall burnout were 9.09, 50.57, 56.59, and 73.98%, respectively. After the statistical analysis, we found that several factors can independently affect the dimensions. Working in the high infection region and negative coping styles can affect all three dimensions at once. More night shift quantity and having symptoms could increase emotional exhaustion and depersonalization, while higher work intensity and senior title could increase emotional exhaustion and reduce personal accomplishment, respectively. Conclusion: The rate of moderate and severe burnout had increased due to the outbreak. More attention should be paid to burnout in HCPs, especially those with negative coping. There were some potential ways to reduce burnout, such as reducing their workload and providing better protection from the virus.

The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by Cryo-EM and Cryo-ET.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized ß-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.