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To control the ongoing coronavirus disease-2019 (COVID-19) pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, the underlying mechanisms of the inactivated COVID-19 vaccine-induced immune response remain unclear, and little is known about its features compared to (Severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection. Here, we implemented single-cell RNA sequencing (scRNA-seq) to profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with CoronaVac and compared these to the profiles of COVID-19 infected patients from a Single Cell Consortium. Both inactivated vaccines and SARS-CoV-2 infection altered the proportion of different immune cell types, caused B cell activation and differentiation, and induced the expression of genes associated with antibody production in the plasma. The inactivated vaccine and SARS-COV-2 infection also caused alterations in peripheral immune activity such as interferon response, inflammatory cytokine expression, innate immune cell apoptosis and migration, effector T cell exhaustion and cytotoxicity, however, the magnitude of change was greater in COVID-19 patients, especially those with severe disease, than in immunized individuals. Further analyses revealed a distinct peripheral immune cell phenotype associated with CoronaVac immunization (HLA class II upregulation and IL21R upregulation in naïve B cells) versus SARS-CoV-2 infection (HLA class II downregulation and IL21R downregulation in naïve B cells from severe disease individuals). There were also differences in the expression of important genes associated with proinflammatory cytokines and thrombosis. In conclusion, this study provides a single-cell atlas of the systemic immune response to CoronaVac immunization and revealed distinct immune responses between inactivated vaccines and SARS-CoV-2 infection.

Background Neurodevelopmental disorders (NDDs) are a group of disorders with high genetic and phenotypic heterogeneities. The 16p11.2 microdeletion has been implicated as an important genetic risk factor for NDDs. Methods Multiple genetic tests were used to detect the 16p11.2 microdeletion from 918 Chinese children with NDDs. Targeted sequencing of genes in the 16p11.2 interval was performed in all carriers of the 16p11.2 microdeletion, and whole‐genome expression profiling analysis was performed for the patient carriers and normal carriers in their intra‐family. Results Three patients carrying the 16p11.2 microdeletion were screened out, indicating a frequency of 0.33% for the 16p11.2 microdeletion in this cohort. We reviewed the neurodevelopmental trajectories of the 16p11.2 microdeletion carriers from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopment, with varied neurodevelopmental phenotypes. A differential PRRT2 genotype (rs10204, T>C) was identified between patients and normal carriers of the 16p11.2 microdeletion. Moreover, the determination of differential whole‐genome expression profiling demonstrated the destruction of the top‐ranked network in neurogenesis and accounted for observation of abnormal neurodevelopmental phenotypes in the 16p11.2 microdeletion carriers. Conclusions We have provided the frequency of the 16p11.2 microdeletion in a Chinese pediatric NDD cohort with a variable NDD phenotype from childhood to puberty, which is useful for Chinese geneticists/pediatricians to conduct the 16p11.2 microdeletion testing in children with NDDs., We screened out three patients carrying 16p11.2 microdeletion from a Chinese pediatric NDD cohort, producing a frequency of 0.33% for 16p11.2 microdeletion, which is useful for Chinese geneticists/pediatricians before conducting the 16p11.2 microdeletion testing in children with NDDs. We reviewed the neurodevelopmental trajectories of these child carriers of 16p11.2 microdeletion from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopmental outcomes, but with varied neurodevelopmental phenotypes. Furthermore, the determination of differential whole‐genome expression profiling between a patient carrier and their intra‐family normal carrier of 16p11.2 microdeletion demonstrated destruction of the top‐ranked network for nervous system development, thus accounting for the observed abnormal neurodevelopmental phenotypes in 16p11.2 microdeletion carriers.

Background Neural tube defects (NTDs) are severe congenital malformations. Diabetes during pregnancy is a risk factor for NTDs, but its mechanism remains elusive. Emerging evidence suggests that protein malonylation is involved in diabetes. Here, we report the correlation between histone lysine malonylation in diabetes‐induced NTDs. Methods Nano‐HPLC/MS/MS was used to screen the histone malonylation profile in human embryonic brain tissue. Then, the histone malonylation level was compared between the brains of normal control mice and mice with diabetes‐induced NTDs. Finally, the histone malonylation level was compared under high glucose exposure in an E9 neuroepithelial cell line (NE4C). Results A total of 30 histone malonylation sites were identified in human embryonic brain tissue, including 18 novel sites. Furthermore, we found an increased histone malonylation level in brain tissues from mice with diabetes‐induced NTDs. Finally, both the histone malonylation modified sites and the modified levels were proved to be increased in the NE4C treated with high glucose. Conclusion Our results present a comprehensive map of histone malonylation in the human fetal brain. Furthermore, we provide experimental evidence supporting a relationship between histone malonylation and NTDs caused by high glucose‐induced diabetes. These findings offer new insights into the pathological role of histone modifications in human NTDs., In this manuscript, we reported, for the first time, the presence of histone malonylation in human fetal brain and mouse neural stem cells. The results reveal that histone malonylation aberrant in diabetes‐induced NTDs. These results may bring a new insight in the pathological role of histone modifications in human NTDs.

Aim Methylation abnormalities in T lymphocytes have been reported to correlate with systemic lupus erythematosus (SLE). Previous studies identified hypomethylation in the promoter of several genes linked to SLE. Long interspersed nucleotide element-1 (LINE-1) constitutes 17–25% of the human genome, and LINE-1 hypomethylation has been reported in SLE. Limited information is available regarding LINE-1 methylation in juvenile SLE (JSLE). Method Methylation levels of LINE-1 in peripheral blood mononuclear cells (PBMCs) from 59 JSLE and 47 control samples were examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Total homocysteine (tHcy) concentrations in plasma were measured by immunoassay. Results Significant hypomethylation of LINE-1 was observed in PBMCs from JSLE patients (60.93% in cases compared with 62.88% in controls, P = 0.001). Significant LINE-1 hypomethylation was observed in active SLE compared to controls (60.66% vs. 62.88%, P = 0.001). According to other clinical parameters, a significant correlation was found between LINE-1 methylation levels and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) of the cases (r = −0.285, P = 0.032). The risk of JSLE increased with decreasing levels of LINE-1 methylation, with an odds ratio of 14.5 (95% CI: 2.8–75.6, P = 0.002). Cases had significantly higher plasma concentrations of tHcy than controls (15.11 vs. 11.02 μmol/L, P = 0.028); the correlation between LINE-1 methylation levels and tHcy was significant (r = −0.4, P = 0.013). Correlations between methylation levels of LINE-1 and complement component 3 were significant (r = 0.317, P = 0.044; r = 0.387, P = 0.031, in total JSLE and active JSLE, respectively). Conclusion Hypomethylation of LINE-1 is associated with risk of JSLE, and LINE-1 methylation levels were related to disease activity and clinical manifestations. The correlation between tHcy levels and LINE-1 methylation was significant.