Formation of Nine-Membered Lactams by Oxidative Ring Expansion of 4-Hydroxyhydroindoles: A Biomimetic Approach toward the Tuberostemonone Ring System?

Formation of Nine-Membered Lactams by Oxidative Ring Expansion of 4-Hydroxyhydroindoles:  A Biomimetic Approach toward the Tuberostemonone Ring System

Formation of Nine-Membered Lactams by Oxidative Ring Expansion of 4-Hydroxyhydroindoles: A Biomimetic Approach toward the Tuberostemonone Ring System?

Formation of Nine-Membered Lactams by Oxidative Ring Expansion of 4-Hydroxyhydroindoles:  A Biomimetic Approach toward the Tuberostemonone Ring System

Table1_Serum albumin levels and risk of atrial fibrillation: a Mendelian randomization study.xls

ObjectiveAlthough several observational studies have linked serum albumin to cardiovascular disease and considered it as an important biomarker, little is known about whether increasing or maintaining serum albumin levels can effectively improve the prognosis of patients with atrial fibrillation. Therefore, this study aims to further explore the causal relationship between serum albumin and atrial fibrillation and its potential mechanism.MethodUsing data from large-scale genome-wide association studies, we conducted a two-sample Mendelian randomization (MR) analysis and a mediation MR analysis, using serum albumin as the exposure variable and atrial fibrillation as the outcome variable. We included 486 serum metabolites as potential mediating factors. To increase the robustness of the analysis, we applied five statistical methods, including inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode. Validate the MR results using Bayesian weighted Mendelian randomization method.ResultThe results of the MR analysis indicate a significant inverse association between genetically predicted serum albumin concentration (g/L) and the risk of atrial fibrillation (Beta = −0.172, OR = 0.842, 95% CI: 0.753–0.941, p = 0.002). Further mediation MR analysis revealed that serum albumin may mediate the causal relationship with atrial fibrillation by affecting two serum metabolites, docosatrienoate and oleate/vaccenate, and the mediating effect was significant. In addition, all our instrumental variables showed no heterogeneity and level-multiplicity in the MR analysis. To verify the stability of the results, we also conducted a sensitivity analysis using the leave-one-out method, and the results further confirmed that our findings were robust and reliable. Finally, we conducted a validation using the Bayesian weighted Mendelian randomization method, which demonstrated the reliability of our causal inference results.ConclusionThis study strongly demonstrates the causal relationship between serum albumin and reduced risk of atrial fibrillation through genetic methods, and reveals the key mediating role of two serum metabolites in this relationship. These findings not only provide a new perspective for our understanding of the role of serum albumin in atrial fibrillation, but also provide new ideas for the prevention and treatment strategies of atrial fibrillation.</p

DataSheet_5_Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses.docx

IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.</p

DataSheet_3_Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses.pdf

IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.</p

DataSheet1_Analysis on intelligent deformation prediction of deep foundation pits with internal support based on optical fiber monitoring and the HSS model.pdf

With the continuous expansion of the city scale, while rapidly advancing foundation pit construction, it has become a top priority to prevent the potential safety hazards caused by efforts to catch up with deadlines. In this case, deep foundation pit monitoring can provide important technical support for the foundation pit design and construction safety. However, conventional foundation pit monitoring for point monitoring of structural characteristics cannot accurately locate local strains and related cracks, and cannot provide real-time monitoring of support structures, ordinary soil constitutive models cannot consider the strain hardening characteristics of soft soil. This paper aimed to analyze the characteristics of excavation deformation of a deep foundation pit with internal support in the Dalian Donggang Business District by combining the methods of optical fiber monitoring and finite element simulation. In this study, distributed optical fiber monitoring and routine monitoring were adopted to carry out the synchronous excavation monitoring of foundation pit support structures. The main monitoring objects were the deep horizontal displacement of the support piles and the surface settlement of the foundation pit. Moreover, the authors used the Plaxis finite element software based on the Hardening Soil-small (HSS) model to conduct the numerical simulation analysis, and the results were compared with two groups of the measured data of the deep foundation pit obtained from the aforementioned research. Additionally, in light of the SSA-BP neural network, the back-analysis method of HSS model parameters in the Dalian area is proposed. The findings show that, under the premise of selecting reasonable parameters, the results of finite element analysis of the HSS model, considering the small strain characteristics of the soil, demonstrate a high degree of fit with the actual deformation law of foundation pits, which proves the rationality of the model. Furthermore, it was verified that the distributed optical fiber monitoring has conspicuous advantages in terms of data continuity and accuracy in contrast to routine monitoring. The research results of this paper can provide reference for deformation monitoring and early warning regarding the support structures of deep foundation pits.</p

DataSheet_4_Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses.pdf

IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.</p

DataSheet_1_Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses.pdf

IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.</p

DataSheet_6_Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses.docx

IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.</p

DataSheet_2_Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses.pdf

IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.</p