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Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to investigate in depth the effect of genetically predicted hip OA on LS risk. Hip OA-related instrumental variables (IVs) were selected from a genome-wide association study (GWAS) of 393,873 individuals. The summary data of LS were obtained from a GWAS meta-analysis, including 16,030 cases and 248,929 controls. We used the inverse-variance weighted (IVW) as the primary MR analysis method. Moreover, the weighted-median, MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were supplementary methods. The sensitivity analysis was performed using the leave-one-out test. We identified the positive causal relationship between hip OA and the risk of LS (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.07, 1.36; p = 0.002 using the IVW method). The weighted median method provided similar results. There was no evidence of directed pleiotropy, and sensitivity analysis results were stable, suggesting the robustness of our study. This study showed a causal effect of hip OA on the risk of LS, and more efforts should be made to explore the potential mechanisms in the future.

In the high intensity areas, the application of interlayer spacing technology can achieve the unity of quality and seismic performance of high-rise buildings with enlarged base and multiple tower layers. Through the comparison and analysis of the structural schemes of an enlarged base multiple tower-layer high-rise building, the ultimate seismic isolation scheme was adopted, and its seismic response and seismic performance were analyzed and studied. The results show that the overall seismic isolation effect of the story isolation technique is good, which can greatly reduce the seismic response, and is an effective means to improve the seismic safety of the structure. Considering the structural characteristics of the project, the improvement of the economy and the quality of the building, the use of story isolation technique in the enlarged base multiple tower-layer structure in the high-intensity region is an optimal scheme. Finally, several key technical issues such as the combined seismic isolation scheme of the enlarged base story isolation technique and the additional bending moment of the isolator and the tensile device of the isolator were discussed, which can provide some references for similar engineering practices.

BackgroundTraditional epidemiological studies suggested that Neurodegenerative diseases (ND) might correlate with stroke. We intend to explore whether the two most common neurodegenerative diseases [Alzheimer’s disease (AD) and Parkinson’s disease (PD)] are causally associated with stroke and its subtypes.MethodsTwo-sample Mendelian Randomization (MR) method was used to explore the causal relationships. Candidate genetic instrumental variables (IVs) for AD and PD were collected from the genome-wide association studies (GWAS) in European populations. The inverse-variance weighted (IVW) method was the primary method of MR analysis, and the weighted median method was supplementary. In addition, the MR-Egger method and the MR-PRESSO test were used as well.ResultsWe found no causal effects of AD on stroke, Ischemic stroke (IS), or Intracerebral hemorrhage (ICH). As for PD and stroke, our preliminary results showed PD could causally influence the risk of stroke [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.02–1.07; P = 0.001 by the IVW method], although the alternative method did not support this result. We identified the positive causal relationship between PD and the risk of IS (OR = 1.04; 95% CI: 1.02–1.07; P = 0.001 by the IVW method), and the alternative MR methods produced similar results. The present study found there was no causal relationship between PD and ICH.ConclusionThis study found a causal relationship between genetic susceptibility to PD and the incidence of stroke (especially IS) in the European population; however, there was no causal relation between AD and stroke risk.

Background: Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR1/ family with sequence similarity 54 (FAM54) family. Recently, it was reported that MTFR2 promotes the proliferation and invasion of breast cancers (BCs). However, the relationship between MTFR2 and endocrine crine therapy resistance is still unknown.Materials and methods: We collected 36 ER+ BC tissues and adjacent normal tissues and 10 samples from patients who received endocrine therapy. We detected the expression pattern of MTFR2 and the fold change in MTFR2 in cells treated with tamoxifen and letrozole. The autophagy status was also determined.Results: MTFR2 expression was upregulated in ER+ BC tissues and was strongly upregulated in the samples that were treated with endocrine therapy. Knocking out MTFR2 increased BC cell sensitivity to endocrine therapy. In addition, MTFR2 directly bound to FUNDC1 and promoted FUNDC1 phosphorylation, thus inhibiting autophagy.Conclusion: Taken together, our results indicate that increased expression of MTFR2 is associated with endocrine therapy resistance in BC cells. Our findings indicate that MTFR2 could serve as a novel therapeutic target for ER+ BC patients who suffer from endocrine therapy resistance.