Evidence for a mouse origin of the SARS-CoV-2 Omicron variant

The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting the possibility of host-jumping. The molecular spectrum (i.e., the relative frequency of the twelve types of base substitutions) of mutations acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients, but was highly consistent with spectra associated with evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.

Differential expression of circular RNA in patients with white matter hyperintensity and cognitive impairment / 中南大学学报(医学版)

OBJECTIVES@#White matter hyperintensity (WMH) is an important factor leading to cognitive impairment, and the mechanism has not been clarified. In recent years, studies have found that circular RNA (circRNA) has differential expression in cerebrovascular diseases. This study aims to analyze the expression profile of circRNA in peripheral blood mononuclear cell (PBMC) of patients with WMH with cognitive impairment, to screen the differentially expressed circRNA, and to explore the possible role of circRNA in WMH with cognitive impairment.@*METHODS@#CircRNA microarray was used to detect the circRNA expression profile of PBMC in patients with WMH with cognitive impairment, and in patients with WMH without cognitive impairment as well as in normal controls (3 cases each, male to female ratio of 2꞉1). The differentially expressed circRNA in patients with WMH with cognitive impairment was screened. The screening criteria for differentially expressed circRNA was fold change (FC) ≥2.0 (|log@*RESULTS@#Compared with the control group, there were 5 significantly up-regulated circRNA and 3 down-regulated circRNA in the WMH with cognitive impairment group; 8 circRNA were significantly up-regulated and 2 were down-regulated in the WMH without cognitive impairment group. When compared with the WMH with cognitive impairment group, no co-differentially expressed circRNA was found in WMH without cognitive impairment group and control group. Compared with the control group, the expression of hsa_circ_0092222 was up-regulated and the expressions of hsa_circ_0000662 and hsa_circ_0083773 were down-regulated in the WMH with cognitive impairment group and the WMH without cognitive impairment group, and there was no significant difference between the 2 groups (all @*CONCLUSIONS@#The circRNA expression profile of patients with WMH is changed significantly. The differentially expressed circRNA may be the cause of WMH; Hsa_circ_0092222, hsa_circ_0000662, and hsa_circ_0083773 may regulate the expression of target genes by targeting adsorption of the target miRNA, leading to brain white matter damage through Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signal pathway and Wnt signal pathway.There is no significant difference in circRNA expression profile between WMH with or without cognitive impairment. Cognitive impairment in patients with WMH may have other reasons.

Crystal structure of Psb27 from Arabidopsis thaliana determined at a resolution of 1.85 Å.

Proper biogenesis and maintenance of photosynthetic thylakoid membrane complexes are essential for the photosynthetic light reactions. A thylakoid lumenal protein, Psb27, plays a vital role in assembly or/and maintenance of photosystem II (PSII). In cyanobacteria, it is a small lipoprotein docked to the lumenal side of PSII, and functions in the assembly of the Mn4Ca cluster and in the PSII repair cycle. However, Psb27 from Arabidopsis thaliana is not a lipoprotein, and it is involved in PSII repair and acclimation to fluctuating light stress, suggesting a functional divergence between Arabidopsis Psb27 and cyanobacterial Psb27s. To gain a better understanding of Psb27 from higher plants, we determined the crystal structure of Arabidopsis Psb27 by X-ray crystallography at a resolution of 1.85 Å. The structure of Arabidopsis Psb27 is a four-helix bundle, similar to its orthologues from cyanobacteria. However, there are several structural differences between Arabidopsis Psb27 and cyanobacterial Psb27s concerning the overall molecular shape, the N- and C-terminal structures, and the surface charge. These differences suggest that Psb27 from higher plants and cyanobacteria may function differently.

Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

Ethical Review on Placebo Control in Ophthalmic New Drug Clinical Trials / 中国医学伦理学

In China , some ophthalmic new drug clinical trials used placebo as control .Two principles should be con-sidered in ethical review when placebo was used in these ophthalmic new drug clinical trials .Firstly, using placebo couldn't lead to irreversible or permanent vision loss .Secondly , there should be proper risk management in protocol and risk dis-closure in consent process .There are several important factors , including effects of standard treatment , risks of using pla-cebo, risk management in protocol and risk information in informed consent form , which should be used to assess the ra-tionality of placebo in ethical review .

Investigation on status quo of medical graduates' professional faith and educational methods / 中华医学教育探索杂志

Objective To understand the status quo of medical graduates' professional faith and to evaluate the education methods. Methods Questionnaire survey combined with expert inter-view were conducted from two aspects: professional faith condition and educational methods. Medical graduates from an affiliated hospital of a university in Shanghai were investigated in this survey and 392 copies of effective questionnaires were analyzed comparatively. Results 92.6%(363/392) students regarded extreme events as the main factor that influence their further employment. 14.8%(58/392) students had career planning. 79.6%(312/392) students achieved self-improvement from strengthening learning and training. Salary was the main factor that affect medical graduates' career choice (4.47 points). 75.5%(296/392) students considered that the existing professional faith education was out of fashion. 85.5%(335/392) of students thought that education methods should be improved. Strengthen-ing relevant education career planning was considered as the most valuable content (4.22 points) and the most effective form was group learning (4.53 points). Conclusions The main reasons for devia-tion and dissatisfaction are:social factor, lack of professional faith, unique status and obsolete way of education. Professional faith education should take the above factors into consideration.

INVESTIGATION ON ASSOCIATION OF SERUM BILIRUBIN CONCENTRATION WITH RISK OF CORONARY HEART DISEASE / 中国医师进修杂志

Objective　 To investigate the relationship between of serum bilirubin concentrations and risk of coronary heart drsease (CHD). Methods　 Serum bilirubin concentrations were determined in 12 cases with acute myocardial infarction(AMI)、37 cases with unstable angina pectoris (UAP) and 30 cases with UAP with arrhythmia. Results　 The serum total bilirubin(TB)、direct bilirubin(DB)、indirect bilirubin(IB) concentrations were lower in the three study groups of CHD than in the controls. There was significant difference between the patients with CHD and the controls. However, there was no significant difference among the three study groups of CHD. Conclusion　 Serum bilirubin concentrations was inversely and statistically significantly related to risk of CHD.