Red and processed meat intake and risk of cardiovascular disease: A two-sample Mendelian randomization study.

BACKGROUND & AIMS: Previous observational studies have yielded inconsistent findings regarding associations between red/processed meat intake and the risk of cardiovascular disease (CVD). Some studies have suggested positive relationships, while others have demonstrated no significant associations. However, causal effects remain uncertain. This 2023 Mendelianrandomization (MR) study investigated the causal relationship between red and processed meat (porkmeat, mutton meat, beef meat)intake and CVD risk by analyzing summary data from the UK Biobank (exposure), CARDIoGRAMplusC4D (coronary artery disease [CAD]), MEGASTROKE (stroke), Nielsen et al. (atrial fibrillation [AF]), HERMES (heart failure [HF]), and FinnGen (cardiovascular outcomes) public databases. METHODS: Genome-wide association studies (GWAS) of red meat (pork, beef, and mutton) and processed meat were sourced from the United Kingdom (UK) Biobank. GWAS data on CVD for this study were obtained from the Gene and FinnGen consortia. The primary method employed for the two-sample MR analysis was inverse variance weighting (IVW). Sensitivity analysis was performed to assess the reliability and consistency of the results. RESULTS: Genetically predicted red and processed meat consumption did not demonstrate a causal association with any CVD outcomes when employing the IVW method. For processed meat intake, the odds ratios (ORs) (95% confidence intervals CIs) in large consortia were as follows: 0.88 (0.56-1.39) for CAD, 0.91 (0.65-1.27) for AF, 0.84 (0.58-1.21) for HF, and 1.00 (0.75-1.05) for stroke. In FinnGen, the ORs were as follows: 1.15 (0.83-1.59) for CAD, 1.25 (0.75-2.07) for AF, 1.09 (0.73-1.64) for HF, and 1.27 (0.85-1.91) for stroke. For beef intake, the ORs (95% CIs) in large consortia were as follows: 0.70 (0.28-1.73) for CAD, 0.85 (0.49-1.49) for AF, 0.80 (0.35-1.83) for HF, and 1.29 (0.85-1.95) for stroke. In FinnGen, the ORs were as follows: 2.01 (0.75-5.39) for CAD, 1.83 (0.60-5.56) for AF, 0.80 (0.30-2.13) for HF, and 1.30 (0.62-2.73) for stroke. For pork intake, the ORs (95% CIs) in large consortia were as follows: 1.25 (0.37-4.22) for CAD, 1.26 (0.73-2.15) for AF, 1.71 (0.86-3.39) for HF, and 1.15 (0.63-2.11) for stroke. In FinnGen, the ORs were as follows: 1.12 (0.43-2.88) for CAD, 0.39 (0.08-1.83) for AF, 0.62 (0.20-1.88) for HF, and 0.60 (0.21-1.65) for stroke. For mutton intake, the ORs (95% CIs) in large consortia were as follows: 0.84 (0.48-1.44) for CAD, 0.84 (0.56-1.26) for AF, 1.04 (0.65-1.67) for HF, and 1.06 (0.77-1.45) for stroke. In FinnGen, the ORs were as follows: 1.20 (0.65-2.21) for CAD, 0.92 (0.44-1.92) for AF, 0.74 (0.34-1.58) for HF, and 0.75 (0.45-1.24) for stroke. The results remained robust and consistent in both the meta-analysis and supplementary MR analysis. CONCLUSIONS: This MR study demonstrated no significant causal relationships between red/processed meat intake and the risk of the four CVD outcomes examined. Further investigation is warranted to confirm these findings.

Stereospecific [3+2] Cycloaddition of Chiral Arylallenes with C,N-Cyclic Azomethine Imines.

A novel α,ß-regioselective [3+2] cycloaddition reaction of arylallene with C,N-cyclic azomethine imine is reported. The axial-to-central chirality transfer phenomenon has been disclosed with chiral allenes in the reaction. The wide substrate scope, including different functional groups and natural products, reveals the generality of the methodology. Both experiments and density functional theory calculations have been used to elucidate a plausible mechanism.

Cesium carbonate-catalyzed synthesis of phosphorothioates via S-phosphination of thioketones.

A highly efficient and environmentally-friendly base-mediated transition metal-free direct thiophilic catalytic approach is reported for the synthesis of S-benzhydryl-phosphorothioates by reacting phosphite nucleophiles with diarylmethanethione. A wide variety of thioketones were coupled with different phosphite derivatives to provide the corresponding phosphorothioates in good to excellent yields. The control experiments and density functional theory (DFT) calculations rely on the regio-selective thiophilic addition of a phosphite nucleophile via umpolung protocols.

Study on the Directional Solidification Process of an Aluminum Alloy Bar in Multishell Mold Being Gradually Immersed in Water.

A multishell mold structure and water-immersion cooling method (MSMWI) is proposed for the directional solidification of castings. A four-layer-shell sand mold was designed for a bar with diameter of 40 mm. As the aluminum melt was poured, the multishell mold was gradually immersed in water, and the water level drove the advancement of the solidification front from bottom to top. The multishell mold was helpful for the heat insulation of its upper part, and its bottom was chilled by the water. Therefore, directional solidification of the bar was vertically realized. The water-cooled solidification process of the bar was 5.8 times faster than that by air natural cooling (MSMNC), and the temperature gradient was increased by 78 times. The secondary dendrite arm spacing (SDAS) and eutectic silicon were significantly refined. Its tensile strength, elongation, and hardness were increased by 56%, 185%, and 62.6%, respectively.

Modeling and Simulation of the Casting Process with Skeletal Sand Mold.

The author-proposed skeletal sand mold, which mainly includes a shell, air cavities and a truss support structure, has been experimentally proven to be very useful in controlling the cooling of casting at local areas and at different periods of the casting process. The modeling and simulation of the casting process using a skeletal sand mold were systemically analyzed. Complicated casting/mold and mold/air boundaries, and the thermal and mechanical behavior of the skeletal sand mold during the casting process were highlighted. A numerical simulation of the casting process of a stress frame specimen using a skeletal sand mold was performed. The temperature, stress and displacement fields of the casting and skeletal sand mold were obtained and compared with those using a traditional sand mold. The simulated results were validated with experiments. Using the skeletal sand mold, the cooling rate of the casting can be greatly improved due to the significant heat release from mold surface to environment. The residual stress and deformation of the casting can be reduced because of the decreased stiffness of this kind of mold. Although the skeletal sand mold is susceptible to cracking, it can be avoided by filleting in the conjunctions and increasing the shell thickness.

Cobalt-Catalyzed Regio- and Stereoselective Hydrosilylation of 1,3-Diynes To Access Silyl-Functionalized 1,3-Enynes.

A regio- and stereoselective hydrosilylation of 1,3-diynes has been developed relying on catalysts generated from bench-stable Co(acac)2 and dppp ligand. A variety of symmetrical and unsymmetrical 1,3-diynes undergo this transformation, yielding the corresponding silyl-functionalized 1,3-enynes in high yields with excellent regioselectivity. Gram-scale reactions and further transformations of the silyl-containing 1,3-enyne products highlight the synthetic utilities of this Co-catalyzed hydrosilylation of 1,3-diynes.

Thiolactone Chemistry-Based Combinatorial Methodology to Construct Multifunctional Polymers for Efficacious Gene Delivery.

Hydrophobic segments and amino moieties in polymeric nonviral gene vectors play important roles in overcoming a cascade of barriers for efficient gene delivery. However, it remains a great challenge to facilely construct well-defined multifunctional polymers through optimization of the amino and hydrophobic groups. Herein, we choose thiolactone chemistry to perform the ring opening reaction of varying hydrophobic groups-modified thiolactones by various amines to generate mercapto groups for further Michael addition reaction with poly[2-(acryloyloxy)ethyl methacrylate] (PAOEMA). Based on the combinatorial methodology, a series of multifunctional polymers were prepared and screened. The polymer (P3D) from tetraethylenepentamine and heptafluorobutyric acid-functionalized thiolactone is the most efficacious one with significantly higher gene transfection efficiency and lower cytotoxicity compared with polyethylenimine (PEI) (branched average Mw ∼ 25 000 Da) and Lipofectamine 2000. Cellular uptake and intracellular distribution studies indicate that P3D complexes show high-efficiency endocytosis and excellent endosomal escape. Accordingly, thiolactone chemistry-based combinatorial methodology allows for facile integration of multifunctional groups to prepare simultaneous efficacious and low-cytotoxic gene delivery vectors.