Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study.

BACKGROUND & AIMS: Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study. METHODS: Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings. RESULTS: ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824-59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013-1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884-0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020-0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743-34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217-51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071-0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476-18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes. CONCLUSIONS: Some glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study.

Background: The gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of gut microbiome with GI cancer has yet to be fully established. We conducted this two-sample Mendelian randomization (MR) study to reveal the potential causal effect of gut microbiota on GI cancer. Materials and methods: Summary-level genetic data of gut microbiome were derived from the MiBioGen consortium and the Dutch Microbiome Project. Summary statistics of six GI cancers were drawn from United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), and weighted-median (WM) methods were used to evaluate the potential causal link between gut microbiota and GI cancer. In addition, we performed sensitivity analyses and reverse MR analyses. Results: We identified potential causal associations between 21 bacterial taxa and GI cancers (values of p < 0.05 in all three MR methods). Among them, phylum Verrucomicrobia (OR: 0.17, 95% CI: 0.05-0.59, p = 0.005) retained a strong negative association with intrahepatic cholangiocarcinoma after the Bonferroni correction, whereas order Bacillales (OR: 1.67, 95% CI: 1.23-2.26, p = 0.001) retained a strong positive association with pancreatic cancer. Reverse MR analyses indicated that GI cancer was associated with 17 microbial taxa in all three MR methods, among them, a strong inverse association between colorectal cancer and family Clostridiaceae1 (OR: 0.91, 95% CI: 0.86-0.96, p = 0.001) was identified by Bonferroni correction. Conclusion: Our study implicates the potential causal effects of specific microbial taxa on GI cancer, potentially providing new insights into the prevention and treatment of GI cancer through specific gut bacteria.

Association Between Autoimmune Diseases and Sarcopenia: A Two-Sample Mendelian Randomization Study.

Purpose: Observational studies have reported that autoimmune diseases are closely related to sarcopenia, but the causalities of autoimmune diseases with sarcopenia have not been established. We conducted this Mendelian randomization (MR) study to reveal the causal associations of overall autoimmune disease and five common autoimmune diseases with sarcopenia-related traits. Methods: The publicly available summary-level data of autoimmune diseases and three sarcopenia-related traits were used for analysis. The causal effects of autoimmune diseases on sarcopenia-related traits were first identified in discovery samples using the inverse-variance-weighted method as the primary method, and the robustness of results was examined by additional sensitivity analyses. Replication MR analyses were then conducted using replication samples of five autoimmune diseases. Finally, the possibility of reverse causation was assessed by reverse MR analyses. Results: In both the discovery and replication samples, we identified potential causal effects of rheumatoid arthritis (RA) on appendicular lean mass (ALM) and low grip strength (OR = 0.979, 95% CI: 0.964-0.995 for ALM; OR = 1.042, 95% CI: 1.013-1.072 for low grip strength), but not on walking pace. We also found that inflammatory bowel disease (IBD) and type 1 diabetes (T1D) were only causally negatively associated with ALM in the discovery stage (OR = 0.986, 95% CI: 0.974-0.999 for IBD; OR = 0.987, 95% CI: 0.975-0.999 for T1D), whereas systemic lupus erythematosus, multiple sclerosis, and overall autoimmune disease were not associated with any of the three sarcopenia-related traits. Additionally, reverse MR analysis only found an association between walking pace and overall autoimmune disease, but this association did not remain in the weighted-median method. Conclusion: This study demonstrates that RA is causally associated with low grip strength and reduced ALM, and that IBD and T1D may be causally negatively related to ALM.

Electrostatic interaction-controlled dispersion of carbon nanotubes in a ternary composite for high-performance supercapacitors.

Effective dispersion of carbon nanotubes (CNTs) is of great importance to achieve their intrinsic performance. Normally, it is believed that CNT dispersion is decided by interactions between CNTs and their dispersants, while other interactions are often neglected. Herein, three ionic surfactants, sodium dodecyl sulfate (SDS), dodecyl dimethyl betaine (BS-12) and cetyltrimethylammonium bromide (CTAB), are used to disperse CNTs in a ternary composite, i.e., poly(p-phenylenediamine)-phosphomolybdic acid@reduced graphene oxide (DMoG), respectively, leading to three different DMoGC composites. It has been found that the CNT dispersion in DMoGC was mainly controlled by electrostatic interactions between the surfactants and DMoG, which further exerted vital influences on the constitution, content, morphology, porous structure and supercapacitive performance of the DMoGC composites. Among the three surfactants, cationic CTAB showed the best CNT dispersion, while amphoteric BS-12 could hardly disperse CNTs in DMoGC, leading to DMoGC-CTAB with a 2 times larger specific surface area (152.3 m2 g-1) and 1.5 times higher specific capacitance (422 F g-1) than those of DMoGC-(BS-12). Our study can provide valuable guidelines for selecting/designing effective dispersants to prepare multi-component composites containing uniformly dispersed CNTs.

Understanding the Evolution of Cobalt-Based Metal-Organic Frameworks in Electrocatalysis for the Oxygen Evolution Reaction.

Metal-organic frameworks (MOFs) have attracted increasing attention as a promising electrode material for the oxygen evolution reaction (OER). Comprehending catalytic mechanisms in the OER process is of key relevance for the design of efficient catalysts. In this study, two types of Co based MOF with different organic ligands (ZIF-67 and CoBDC; BDC=1,4-benzenedicarboxylate) are synthesized as OER electrocatalysts and their electrochemical behavior is studied in alkaline solution. Physical characterization indicates that ZIF-67, with tetrahedral Co sites, transforms into α-Co(OH)2 on electrochemical activation, which provides continuous active sites in the following oxidation, whereas CoBDC, with octahedral sites, evolves into ß-Co(OH)2 through hydrolysis, which is inert for the OER. Electrochemical characterization reveals that Co sites coordinated by nitrogen from imidazole ligands (Co-N coordination) are more inclined to electrochemical activation than Co-O sites. The successive exposure and accumulation of real active sites is responsible for the gradual increase in activity of ZIF-67 in OER. This work not only indicates that CoMOFs are promising OER electrocatalysts but also provides a reference system to understand how metal coordination in MOFs affects the OER process.

A covalently linked dual network structure achieved by rapid grafting of poly(p-phenylenediamine)-phosphomolybdic acid on reduced graphene oxide aerogel for improving the performance of supercapacitors.

Covalent grafting of poly(p-phenylenediamine) (PPD)-phosphomolybdic acid (PMo12) on rGO (PPD-PMo12@rGO) has been realized within 1 minute. PPD-PMo12@rGO shows a characteristic covalently linked dual network structure that can significantly enhance its specific capacitance and cycling stability for supercapacitor applications.

Ethylenediamine-Catalyzed Preparation of Nitrogen-Doped Hierarchically Porous Carbon Aerogel under Hypersaline Condition for High-Performance Supercapacitors and Organic Solvent Absorbents.

The simple and cost-efficient preparation of high-performance nitrogen-doped carbon aerogel (N-CA) for supercapacitors and other applications is still a big challenge. In this work, we have presented a facile strategy to synthesize hierarchically porous N-CA, which is based on solvothermal polymerization of phenol and formaldehyde under hypersaline condition with ethylenediamine (EDA) functioning as both a catalyst and a nitrogen precursor. Benefited from the catalytic effect of EDA on the polymerization, the obtained N-CA has a predominant amount of micropores (micropore ratio: 52%) with large specific surface area (1201.1 m2·g-1). In addition, nitrogen doping brings N-CA enhanced wettability and reduced electrochemical impedance. Therefore, the N-CA electrode shows high specific capacitance (426 F·g-1 at 1 A·g-1 in 0.5 M H2SO4) and excellent cycling stability (104% capacitance retention after 10,000 cycles) in three-electrode systems. Besides, a high energy density of 32.42 Wh·kg-1 at 800 W·kg-1 can be achieved by symmetric supercapacitor based on the N-CA electrodes, showing its promising application for energy storage. Furthermore, N-CA also exhibits good capacity and long recyclability in the absorption of organic solvents.