Visible-Light-Induced, Copper-Catalyzed Three-Component Coupling of Alkyl Halides, Olefins, and Trifluoromethylthiolate to Generate Trifluoromethyl Thioethers

Photoinduced, copper-catalyzed coupling reactions are emerging as a powerful method for generating Csp^3–Y (Y = C or heteroatom) bonds from alkyl electrophiles and nucleophiles. Corresponding three-component couplings of alkyl electrophiles, olefins, and nucleophiles have the potential to generate an additional Csp3–Y bond and to efficiently add functional groups to both carbons of an olefin, which serves as a readily available linchpin. In this report, we establish that a variety of electrophiles and a trifluoromethylthiolate nucleophile can add across an array of olefins (including styrenes and electron-poor olefins) in the presence of CuI/binap and blue-LED irradiation, thereby generating trifluoromethyl thioethers in good yield. The process tolerates a wide range of functional groups, and an initial survey of other nucleophiles (i.e., bromide, cyanide, and azide) suggests that this three-component coupling strategy is versatile. Mechanistic studies are consistent with a photoexcited Cu(I)/binap/SCF_3 complex serving as a reductant to generate an alkyl radical from the electrophile, which likely reacts in turn with the olefin and a Cu(II)/SCF_3 complex to afford the coupling product

Visible-Light-Induced, Copper-Catalyzed Three-Component Coupling of Alkyl Halides, Olefins, and Trifluoromethylthiolate to Generate Trifluoromethyl Thioethers

Photoinduced, copper-catalyzed coupling reactions are emerging as a powerful method for generating Csp^3–Y (Y = C or heteroatom) bonds from alkyl electrophiles and nucleophiles. Corresponding three-component couplings of alkyl electrophiles, olefins, and nucleophiles have the potential to generate an additional Csp3–Y bond and to efficiently add functional groups to both carbons of an olefin, which serves as a readily available linchpin. In this report, we establish that a variety of electrophiles and a trifluoromethylthiolate nucleophile can add across an array of olefins (including styrenes and electron-poor olefins) in the presence of CuI/binap and blue-LED irradiation, thereby generating trifluoromethyl thioethers in good yield. The process tolerates a wide range of functional groups, and an initial survey of other nucleophiles (i.e., bromide, cyanide, and azide) suggests that this three-component coupling strategy is versatile. Mechanistic studies are consistent with a photoexcited Cu(I)/binap/SCF_3 complex serving as a reductant to generate an alkyl radical from the electrophile, which likely reacts in turn with the olefin and a Cu(II)/SCF_3 complex to afford the coupling product

Refining microstructure of medium-thick AA2219 aluminium alloy welded joint by ultrasonic frequency double-pulsed arc

The increasing demand for achieving high-efficiency and high-quality medium-thick aluminium alloy welded structures, especially for large scale aerospace components, presents an urgent challenge to the conventional TIG arc welding process. This work proposed a novel double-pulsed variable polarity tungsten inert gas (DP-VPTIG) arc, in which the variable polarity square wave current was simultaneously modulated into ultrasonic frequency (20–80 kHz) and low frequency (0.5–10 Hz) pulses. Full penetration welds of 6 mm thick AA2219 aluminum alloy were successfully obtained by using this process. The microstructure and mechanical properties of the weld produced by DP-VPTIG arc were investigated, taking the conventional VPTIG arc as a comparative study. Results show that the microstructure of weld zone by DP-VPTIG arc showed an alternating distribution of fine equiaxed grain band and slightly coarse equiaxed grain band. Compared to VPTIG arc, the grain structure was effectively refined in the weld zone with DP-VPTIG arc, showing a significant reduction of average grain size by 51.2% along transverse section and 61.3% along longitudinal section. The morphology of α-Al+θ-CuAl2 eutectics transformed from continuously distributed netlike shape to separately distributed granular shape, and segregation of Cu solute element was obviously improved. The average microhardness of weld zone was increased by about 8.7% and 5.6% along transverse section and along longitudinal section. The tensile properties of ultimate tensile strength, yield strength and elongation were increased by 6.6%, 10.6% and 20.5%, respectively. The results provide a valuable basis for improving welding efficiency and joint quality through a hybrid pulsed arc

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p

The genetic correlation and causal association between key factors that influence vascular calcification and cardiovascular disease incidence

Background: Serum calcium (Ca), vitamin D (VD), and vitamin K (VK) levels are key determinants of vascular calcification, which itself impacts cardiovascular disease (CVD) risk. The specific relationships between the levels of these different compounds and particular forms of CVD, however, remain to be fully defined. Objective: This study was designed to explore the associations between these serum levels and CVDs with the goal of identifying natural interventions capable of controlling vascular calcification and thereby protecting against CVD pathogenesis, extending the healthy lifespan of at-risk individuals.Methods: Linkage disequilibrium score (LDSC) regression and a two-sample Mendelian randomization (MR) framework were leveraged to systematically examine the causal interplay between these serum levels and nine forms of CVD, as well as longevity through the use of large publically accessible Genome-Wide Association Studies (GWAS) datasets. The optimal concentrations of serum Ca and VD to lower CVD risk were examined through a restrictive cubic spline (RCS) approach.Results: After Bonferroni correction, the positive genetic correlations were observed between serum Ca levels and myocardial infarction (MI) (p = 1.356E–04), as well as coronary artery disease (CAD) (p = 3.601E–04). Negative genetic correlations were detected between levels of VD and CAD (p = 0.035), while elevated VK1 concentrations were causally associated with heart failure (HF) [odds ratios (OR) per 1-standard deviation (SD) increase: 1.044], large artery stroke (LAS) (OR per 1-SD increase: 1.172), and all stroke (AS) (OR per 1-SD increase: 1.041). Higher serum Ca concentrations (OR per 1-SD increase: 0.865) and VD levels (OR per 1-SD increase: 0.777) were causally associated with reduced odds of longevity. These findings remained consistent in sensitivity analyses, and serum Ca and VD concentrations of 2.376 mmol/L and 46.8 nmol/L, respectively, were associated with a lower CVD risk (p &lt; 0.001). Conclusion: Our findings support a genetic correlation between serum Ca and VD and CVD risk, and a causal relationship between VK1 levels and CVD risk. The optimal serum Ca (2.376 mmol/L) and VD levels (46.8 nmol/L) can reduce cardiovascular risk.</p