No abstract

Integrated single-cell RNA sequencing technologies reveal a high-resolution immune landscape of colorectal primary tumors and liver metastasis, identifying major immune cell types and distinct cell functional states of T and B cells as well as predictions of complex cell-cell interactions.

Background Several studies have demonstrated that coronary heart disease (CHD) is a high risk factor for cognitive impairment, whereas other studies showed that there was no association between cognitive impairment and CHD. The relationship between CHD and cognitive impairment is still unclear based on these conflicting results. Thus, it is of importance to evaluate the association between CHD and cognitive impairment. The present study made a meta‐analysis to explore the association between CHD and risk of cognitive impairment. Methods Articles exploring the association between CHD and cognitive impairment and published before November 2020 were searched in the following databases: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We used STATA 12.0 software to compute the relative risks (RRs), odds ratios (ORs), or hazard ratios (HRs) and 95% confidence intervals (CIs). Results The meta‐analysis showed a positive association between CHD and risk of all‐cause cognitive impairment with a random effects model (RR = 1.27, 95% CI 1.18 to 1.36, I2 = 82.8%, p < .001). Additionally, the study showed a positive association between myocardial infraction (MI) and risk of all‐cause cognitive impairment with a random effects model (RR = 1.49, 95% CI 1.20 to 1.84, I2 = 76.0%, p < .001). However, no significant association was detected between angina pectoris (AP) and risk of all‐cause cognitive impairment with a random effects model (RR = 1.23, 95% CI 0.95 to 1.58, I2 = 79.1%, p < .001). Subgroup studies also showed that CHD patients are at higher risk for vascular dementia (VD), but not Alzheimer's disease (AD) (VD: RR = 1.34, 95% CI: 1.28–1.39; AD: RR = 0.99, 95% CI: 0.92–1.07). Conclusion In a word, CHD was significantly associated with an increased risk of developing cognitive impairment.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of α-synuclein (α-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of α-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P < 0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of α-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson's disease.

The present study ascertains that L444P mutation in GBA gene may contribute to an earlier onset of development of PD in Han/Chinese population. Following LRRK2 variants, GBA is the second most frequent mutations indicated for sporadic PD development in the Han/Chinese population. These GBA carriers are associated with an earlier onset of Parkinsonism.