The protective role of oily fish intake against type 2 diabetes: insights from a genetic correlation and Mendelian randomization study.

Background and aims: Previous research has underscored the association between oily fish intake and type 2 diabetes (T2DM), yet the causality remains elusive. Methods: A bidirectional univariable Mendelian Randomization (MR) analysis was employed to evaluate the causal effects of oily fish and non-oily fish intake on T2DM. Replication analysis and meta-analysis were conducted to ensure robust results. Multivariable MR analysis was utilized to assess confounders, and further mediation MR analysis discerned mediating effects. Linkage Disequilibrium Score (LDSC) analysis was undertaken to compute genetic correlations. Inverse variance weighted (IVW) was the primary method, complemented by a series of sensitivity analyses. Results: The LDSC analysis unveiled a significant genetic correlation between oily fish intake and T2DM (Genetic correlation: -0.102, p = 4.43 × 10-4). For each standard deviation (SD) increase in genetically predicted oily fish intake, the risk of T2DM was reduced by 38.6% (OR = 0.614, 95% CI 0.504 ~ 0.748, p = 1.24 × 10-6, False Discovery Rate (FDR) = 3.72 × 10-6). The meta-analysis across three data sources highlighted a persistent causal association (OR = 0.728, 95% CI 0.593 ~ 0.895, p = 0.003). No other causal effects were identified (all p > 0.5, FDR > 0.5). The main outcomes remained consistent in most sensitivity analyses. Both MVMR and mediation MR analyses emphasized the mediating roles of triglycerides (TG), body mass index (BMI), and 25-hydroxyvitamin D (25OHD) levels. Conclusion: To encapsulate, there's an inverse association between oily fish intake and T2DM risk, suggesting potential benefits of oily fish intake in T2DM prevention.

Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis.

BACKGROUND: Previous studies have emphasized the association between the intake of artificial sweeteners (AS) and type 2 diabetes mellitus (T2DM), but the causative relationship remains ambiguous. METHODS: This study employed univariate Mendelian randomization (MR) analysis to assess the causal link between AS intake from various sources and T2DM. Linkage disequilibrium score (LDSC) regression was used to evaluate the correlation between phenotypes. Multivariate and mediation MR were applied to investigate confounding factors and mediating effects. Data on AS intake from different sources (N = 64,949) were sourced from the UK Biobank, while T2DM data were derived from the DIAbetes Genetics Replication And Meta-analysis.The primary method adopted was inverse variance weighted (IVW), complemented by three validation techniques. Additionally, a series of sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. RESULTS: LDSC analysis unveiled a significant genetic correlation between AS intake from different sources and T2DM (rg range: -0.006 to 0.15, all P < 0.05). After correction by the false discovery rate (FDR), the primary IVW method indicated that AS intake in coffee was a risk factor for T2DM (OR = 1.265, 95% CI: 1.035-1.545, P = 0.021, PFDR = 0.042). Further multivariable and mediation MR analyses pinpointed high density lipoprotein-cholesterol (HDL-C) as mediating a portion of this causal relationship. In reverse MR analysis, significant evidence suggested a positive correlation between T2DM and AS intake in coffee (ß = 0.013, 95% CI: 0.004-0.022, P = 0.004, PFDR = 0.012), cereal (ß = 0.007, 95% CI: 0.002-0.012, P = 0.004, PFDR = 0.012), and tea (ß = 0.009, 95% CI: 0.001-0.017, P = 0.036, PFDR = 0.049). No other causal associations were identified (P > 0.05, PFDR > 0.05). CONCLUSION: The MR analysis has established a causal relationship between AS intake in coffee and T2DM. The mediation by HDL-C emphasizes potential metabolic pathways underpinning these relationships.

Genetic Insights into the causal relationship between cannabis use and diabetic phenotypes: A genetic correlation and Mendelian randomization study.

BACKGROUND: Previous studies have highlighted the association between cannabis use and diabetes and its complications; however, the causality remains ambiguous. METHODS: Univariate Mendelian randomization (MR), multivariate MR, mediation MR, and linkage disequilibrium score (LDSC) analysis to assess the causal relationship between cannabis use and 12 diabetic phenotypes. Summary statistics for lifetime cannabis use (N = 184,765) and cannabis use disorder (CUD) (N = 374,287) from genome-wide association studies. The primary method used was inverse-variance-weighted (IVW). A range of sensitivity analyses ensured the robustness of the results. RESULTS: LDSC analysis revealed a significant genetic correlation between CUD and T2DM, as well as between lifetime cannabis use and four diabetic phenotypes (P < 0.05). After correction by false discovery rate (FDR), the primary IVW analysis indicates that the genetically predicted CUD is positively associated with the risk of diabetic hypoglycemia (OR = 1.11, 95% CI 1.04-1.20, P = 0.003, PFDR = 0.04) and proliferative diabetic retinopathy (PDR) (OR = 1.12, 95% CI 1.04-1.19, P = 4.89×10-4, PFDR =0.01). Additionally, suggestive evidence links CUD with increased risks of diabetic nephropathy, type 1 diabetes mellitus (T1DM), diabetic retinopathy, and T1DM associated with diabetic ketoacidosis (P < 0.05 & PFDR > 0.05). No causal relationship was detected between lifetime cannabis use and diabetic phenotypes (P > 0.05 & PFDR > 0.05). Multivariable and mediation MR analyses revealed that glycated hemoglobin A1c partially mediates the causal effect of CUD on PDR and diabetic hypoglycemia. CONCLUSION: This MR study suggests that CUD may have a causal role in several diabetic disease phenotypes.

Serum uric acid and risk of diabetic neuropathy: a genetic correlation and mendelian randomization study.

Background: Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality have left the causality of this relationship uncertain. Methods: Univariate Mendelian randomization (MR), multivariate MR and linkage disequilibrium score (LDSC) regression analysis were utilized to assess the causal link between SUA and DN. Summary-level data for SUA were drawn from the CKDGen consortium, comprising 288,648 individuals, while DN data were obtained from the FinnGen consortium, with 2,843 cases and 271,817 controls. Causal effects were estimated primarily using inverse variance weighted (IVW) analysis, supplemented by four validation methods, with additional sensitivity analyses to evaluate pleiotropy, heterogeneity, and result robustness. Results: The LDSC analysis revealed a significant genetic correlation between SUA and DN (genetic correlation = 0.293, P = 2.60 × 10-5). The primary methodology IVW indicated that each increase of 1 mg/dL in SUA would increase DN risk by 17% (OR = 1.17, 95% CI 1.02-1.34, P = 0.02), while no causal relationship was found in reverse analysis (OR = 1.00, 95% CI 0.98~1.01, P = 0.97). Multivariate MR further identified that the partial effect of SUA on DN may be mediated by physical activity, low density lipoprotein cholesterol (LDL-C), insulin resistance (IR), and alcohol use. Conclusion: The study establishes a causal link between elevated SUA levels and an increased risk of DN, with no evidence for a reverse association. This underscores the need for a comprehensive strategy in DN management, integrating urate-lowering interventions with modulations of the aforementioned mediators.

Fabrication of Highly Luminescent Quasi Two-Dimensional CsPbBr3 Perovskite Films in High Humidity Air for Light-Emitting Diodes.

Perovskite light-emitting diodes (LEDs) have attracted extensive attention in recent years due to their outstanding performance and promise in lighting and display applications. However, the fabrication of perovskite LEDs usually requires a low-humidity atmosphere, which is unfavorable for industrial production. Herein, we report an effective strategy to fabricate highly luminescent quasi two-dimensional CsPbBr3 perovskite films in an ambient atmosphere with a humidity up to 60%. We reveal that the hole transport layer (HTL) plays a significant role in the morphology and optical properties of the perovskite films. Using hydrophobic self-assembled monolayer materials as HTLs can remarkably improve the quality of the perovskite films processed in high humidity air. The resultant perovskite LEDs show reduced leakage current and significantly enhanced performance. Furthermore, surface treatment is conducted to prevent water invasion and promote radiative recombination in perovskite films and LEDs. Eventually, the perovskite LEDs exhibit bright green emission with an external quantum efficiency of 4.87%. The present work provides a feasible pathway to overcome the humidity limitation for obtaining bright perovskite films and LEDs, which would contribute to further reducing the fabrication cost of perovskite LEDs and promoting their applications.

Control of n-Phase Distribution in Quasi Two-Dimensional Perovskite for Efficient Blue Light-Emitting Diodes.

Pure-bromide quasi-2D perovskite (PBQ-2DP) promises high-performance light-emitting diodes (LEDs), while a challenge remains on control over its n-phase distribution for bright true-blue emission. Present work addresses the challenge through exploring the passivation molecule of amino acid with reinforced binding energy, which generates narrow n-phase distribution preferentially at n = 3 with true blue emission at 478 nm. Consequently, a peak external quantum efficiency of 5.52% and a record brightness of 512 cd m-2 are achieved on the PBQ-2DP-based true blue PeLED, these both values located among the top in the records of similar devices. We further reveal that the electron-phonon coupling results in the red-shifted emission in the PBQ-2DP film, suggesting that the view of n-phase distribution dominated true-blue emission in PBQ-2DP needs to be revisited, pointing out a guideline of electron-phonon coupling suppression to relieve the strait of realizing true blue or even deep blue emission in the PBQ-2DP film.

Genetic association and bidirectional Mendelian randomization for causality between gut microbiota and six lung diseases.

Purposes: Increasing evidence suggests that intestinal microbiota correlates with the pathological processes of many lung diseases. This study aimed to investigate the causality of gut microbiota and lung diseases. Methods: Genetic information on intestinal flora and lung diseases [asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), lower respiratory tract infection (LRTI), pulmonary arterial hypertension (PAH)] and lung function was obtained from UK Biobank, FinnGen, and additional studies. A Mendelian randomization (MR) analysis was conducted to explore the causal association between gut microbiota and lung diseases. Results: The genetic liability to lung diseases may be associated with the abundance of certain microbiota taxa. Specifically, the genus Prevotella (p = 0.041) was related to a higher risk of asthma; the family Defluviitaleaceae (p = 0.002) and its child taxon were identified as a risk factor for chronic bronchitis; the abundance of the genus Prevotella (p = 0.020) was related to a higher risk of ILD; the family Coriobacteriaceae (p = 0.011) was identified to have a positive effect on the risk of LRTI; the genus Lactobacillus (p = 0.0297) has been identified to be associated with an increased risk of PAH, whereas the genus Holdemanella (p = 0.0154) presented a causal decrease in COPD risk; the order Selenomonadales was identified to have a positive effect on the risk of FEV1(p = 0.011). The reverse TSMR analysis also provided genetic evidence of reverse causality from lung diseases to the gut microbiota. Conclusion: This data-driven MR analysis revealed that gut microbiota was causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between gut microbiota and lung diseases.

The effect of antioxidant dietary supplements and diet-derived circulating antioxidants on vitiligo outcome: evidence from genetic association and comprehensive Mendelian randomization.

Background: Previous studies have indicated that antioxidant diets may have a positive impact on vitiligo by interfering with oxidative stress mechanisms. However, there has been a lack of research utilizing the Mendelian randomization (MR) method to analyze the relationship between antioxidant diet intake and vitiligo. Methods: In this study, we employed both univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) approaches. The specific antioxidant dietary supplements (such as coffee intake, green tea intake, herbal tea intake, standard tea intake, and average weekly red wine intake) as well as diet-derived circulating antioxidants, including Vit. C (ascorbate), Vit. E (α-tocopherol), Vit. E (γ-tocopherol), Carotene, Vit. A (retinol), Zinc, and Selenium (N = 2,603-428,860) were significantly associated with independent single-nucleotide polymorphisms (SNPs). We obtained pooled statistics on vitiligo from a meta-analysis of three genome-wide association studies (GWASs) of European ancestry, including 4,680 cases and 39,586 controls. Inverse variance weighted (IVW) was employed as the primary analytical method, and sensitivity analysis was conducted to assess the robustness of the main findings. Results: Genetically, coffee intake [odds ratio (OR) = 0.17, 95% confidence interval (CI) 0.07-0.37, p = 1.57 × 10-5], average weekly red wine intake (OR = 0.28, 95% CI 0.08-1.00, p = 0.049), and standard tea intake (OR = 0.99, 95% CI 0.98-0.99, p = 5.66 × 10-7) were identified as protective factors against vitiligo. However, no causal effect between the intake of other antioxidant diets and vitiligo was found. Moreover, no instances of pleiotropy or heterogeneity were observed in this study. Conclusion: Our study indicates that coffee, standard tea, and red wine consumption can potentially reduce the risk of vitiligo. However, there is insufficient evidence to support that other antioxidant diets have a significant effect on vitiligo.

Retraction of "lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells".

[This retracts the article DOI: 10.1515/med-2021-0406.].

Mitigating Voc Loss in Tin Perovskite Solar Cells via Simultaneous Suppression of Bulk and Interface Nonradiative Recombination.

Tin-based perovskite solar cells (PSCs) have recently attracted extensive attention as a promising alternative to lead-based counterparts due to their low toxicity and narrow band gap. However, the severe open-circuit voltage (Voc) loss remains one of the most significant obstacles to further improving photovoltaic performance. Herein, we report an effective approach to reducing the Voc loss of tin-based PSCs. We find that introducing ethylammonium bromide (EABr) as an additive into the tin perovskite film can effectively reduce defect density both in the tin perovskite film and at the surface as well as optimize the energy level alignment between the perovskite layer and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) transport material, thereby suppressing nonradiative recombination both in the bulk film and at the interface. Furthermore, it is demonstrated that the Voc loss is gradually mitigated along with increasing storage duration due to the slow passivation effect. As a result, a remarkable Voc of 0.83 V is achieved in the devices optimized with the EABr additive, which shows a significantly improved power conversion efficiency (PCE) of 10.80% and good stability.

lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells.

Gastric cancer (GC) is one of the most common malignancies in digestive system. Accumulating evidence reveals the critical role of long noncoding RNAs (lncRNAs) in GC development. The study aimed to explore the functions and mechanism of lncRNA actin alpha 2, smooth muscle antisense RNA 1 (ACTA2-AS1) in GC. Reverse transcription-quantitative polymerase chain reaction analyses and subcellular fractionation assays showed that ACTA2-AS1 was lowly expressed in GC cells and was mainly distributed in the cytoplasm. Overexpressed ACTA2-AS1 inhibited GC cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition process, as suggested by cell counting kit-8 assays, colony formation assays, wound healing assays, Transwell assays and Western blot analyses. Mechanistically, ACTA2-AS1 served as a competing endogenous RNA (ceRNA) to bind with miR-378a-3p and thereby, antagonized the inhibitory effect of miR-378a-3p on the expression of messenger RNA phosphatidylinositol specific phospholipase C X domain containing 2 (PLCXD2). The binding capacity between miR-378a-3p and ACTA2-AS1 (or PLCXD2) was detected by RNA pulldown assays, luciferase reporter assays and RNA immunoprecipitation assays. Moreover, PLCXD2 knockdown rescued the inhibitory effect of ACTA2-AS1 overexpression on malignant behaviors of GC cells. Overall, ACTA2-AS1 inhibits malignant phenotypes of GC cells by acting as a ceRNA to target miR-378a-3p/PLCXD2 axis.

Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis.

Previous studies have found that telomerase reverse transcriptase (TERT) has vital roles in the development of malignant diseases including glioma. The occurrence of TERT promoter mutations in gliomas is frequent. So far, several studies on the association between TERT promoter mutations and prognosis of gliomas had been published, but the conclusion was still not uncertain. The aim of the present meta-analysis was to assess the association between TERT promoter mutations and survival of glioma patients by pooling data from published studies. PubMed, Embase, and Web of Science were searched for articles on the association between TERT promoter mutations and survival of glioma patients until June 30, 2015. Hazard ratios (HR) and the 95% confidence intervals (CIs) were utilized to analyze the prognosis of glioma patients with TERT promoter mutations. Heterogeneity of included studies was assessed using Cochrane's Q test and I (2) method. Eleven studies with a total of 3,444 glioma patients were finally included into the meta-analysis. Nine studies reported the HRs adjusting for other confounding factors. Meta-analysis of total 11 studies suggested that TERT promoter mutations were significantly associated with worse prognosis of patients with gliomas (HR = 2.07, 95% CI = 1.58-2.71, P < 0.00001). Meta-analysis of nine studies with adjusted outcomes suggested that TERT promoter mutations were independently associated with worse prognosis of patients with gliomas (HR = 2.28, 95% CI = 1.72-3.01, P < 0.00001). In conclusion, TERT promoter mutation is a promising biomarker for predicting worse prognosis for patients with gliomas. More prospective well-designed cohort studies are needed to further validate its prognostic role in gliomas.

Diagnostic accuracy of EUS and CT of vascular invasion in pancreatic cancer: a systematic review.

OBJECTIVE: The objective of this study was to summarize the accuracy of preoperative vascular invasion with endoscopic ultrasound (EUS) and computed tomography (CT) test performance in pancreatic cancer with meta-analysis METHOD: Two reviewers searched MEDLINE database to identify relevant studies. The reference lists of the trials were manually searched. Included studies used surgical and/or histological findings as the "gold standard," and provided sufficient data to construct a diagnostic 2 × 2 table. A statistical program of Meta-Disc was used to calculate the pooled sensitivity, specificity, positive LR, negative LR, DOR, and the SROC curve. Publication bias was assessed by Deeks' asymmetry test. Sensitivity analysis and subgroup analysis were calculated to down the heterogeneity. Meta-regression was calculated to evaluate potential sources of heterogeneity RESULT: A total of 30 studies with 1,554 patients were included for the analysis, nine of these studies compared EUS with CT to assess the diagnostic efficiency The pooled sensitivity of EUS and CT was 72 % (95 % CI 67-77 %) and 63 % (95 % CI 58-67 %), and the pooled specificity of EUS and CT was 89 % (95 % CI 86-92 %) and 92 % (95 % CI 90-94 %), respectively. The positive LR of EUS and CT was 5.14 (95 % CI 3.14-8.40) and 6.21 (95 % CI 3.96-9.71), and the negative LR was 0.36 (95 % CI 0.25-0.52) and 0.41 (95 % CI 0.31-0.55), respectively. The AUCs of EUS and CT were 0.9037 and 0.8948. The subgroup analysis of nine studies performed both EUS and CT showed CT scan with a lower sensitivity of 48 % (95 % CI 0.40-0.56), when compared to EUS of 69 % (95 % CI 0.61-0.77). The overall AUCs of CT scan appear to be lower (AUCs = 0.8589), compared with EUS (AUCs = 0.9379) CONCLUSION: EUS performed better than CT in differentiating vascular invasion preoperative on pancreatic cancer. EUS could provide other additional information when compared with CT.