S1-S18 Figs are included in the file.

BackgroundNumerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.MethodsFor the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.ResultsAfter adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261–12.432; P P P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.ConclusionOur findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.</div

Study design of MR.

Three core assumptions were as follows: (1) Relevance assumption, the genetic variants must be associated with exposure (milk with different fat content); (2) Independence assumption, the genetic variants should not be associated with confounders; (3) Exclusion restriction, the genetic variants must influence outcome (coronary artery disease and myocardial infarction) only via exposure.</p

S1-S12 Tables are included in the file.

BackgroundNumerous observational studies have investigated on the correlation of whole, semi-skimmed, and skimmed milk with coronary artery disease (CAD) and myocardial infarction (MI) risk; However, no consensus has been reached and evidence on any causal links between these exposures and outcomes remains unclear. This study aimed to conduct univariate and multivariate Mendelian randomization (MR) analyses, using publicly released genome-wide association study summary statistics (GWAS) from the IEU GWAS database, to ascertain the causal association of milk with various fat content with CAD and MI risk.MethodsFor the exposure data, 29, 15, and 30 single-nucleotide polymorphisms for whole milk, semi-skimmed milk, and skimmed milk, respectively, obtained from 360,806 Europeans, were used as instrumental variables. CAD and MI comprised 141,217 and 395,795 samples, respectively. We used inverse variance weighted (IVW), weighted median, MR-Egger regression, and MR Pleiotropy Residual Sum and Outlier analyses to determine whether pleiotropy and heterogeneity could skew the MR results. Sensitivity tests were conducted to verify the robustness of the results.ResultsAfter adjusting for false discovery rates (FDR), we discovered proof that skimmed milk intake is a genetically predicted risk factor for CAD (odds ratio [OR] = 5.302; 95% confidence interval [CI] 2.261–12.432; P P P = 0.010; FDR-corrected P = 0.009). Most sensitivity assessments yielded valid results. Multivariable MR for CAD and MI produced results consistent with those obtained using the IVW method. There was no causal relationship between whole or semi-skimmed milk, and CAD or MI.ConclusionOur findings indicate that the consumption of skimmed milk may increase the risk of CAD and MI. This evidence may help inform dietary recommendations for preventing cardiovascular disease. Further studies are required to elucidate the underlying mechanisms.</div

Associations of whole, semi-skimmed, and skimmed milk with coronary artery disease and myocardial infarction.

CI, confidence interval; OR, odds ratio; SNP, single-nucleotide polymorphism; P-adjusted, FDR-corrected P.</p

The TIP30 protein complex, arachidonic acid and coenzyme A promote the fusion between endocytic and Rab5a vesicles.

<p>(<b>A</b>) Aliquots of isolated EGFR-DsRed and EYFP-Rab5a vesicles (both contain 20 µg of proteins) were mixed and incubated in reactions (20 µl) with the indicated components. The resulting fusion products were spotted on glass slides and images were taken using confocal microscope. Panels 1, 4 and 6 were scanned with 3× amplification gain setting due to lower fluorescence intensity of individual vesicles. Arachidonic acid (100 nmol) was used in the reactions. Images are single plane and are representative for at least three independent experiments. Scale bars, 5 µm. (<b>B</b>) Signal overlap was quantified using MBF_ImageJ. Pearson's colocalization coefficients were calculated from three independent experiments and were converted to percentages. Data represent means ± SEM. **<i>P</i><0.01, ***<i>P</i><0.001; t test. (<b>C</b>) Arachidonic acid promotes the vesicle fusion induced by HeLa cell S100. S100 fractions (4 mg/ml) of HeLa cells were incubated with isolated EGFR-DsRed and EYFP-Rab5a vesicles (both contain 20 µg proteins) in the absence or presence of 100 nmol arachidonic acid. Resulting vesicles were examined using confocal microscopy (left panel) and fluorescence overlaps were quantified (right panel).</p

DataSheet1_Impact of land use and land cover change on the landscape pattern and service value of the village ecosystem in the karst desertification control.docx

Human activities have had a significant impact on ecosystems. Studying landscape patterns and ecosystem services (ES) at the village scale based on land use and land cover (LULC) is essential in addressing current ecosystem issues. Based on GF images, the paper selects village ecosystems of karst desertification control (KDC) as the research object. It uses the landscape pattern index, topographic position index (TPI), and value equivalent method to conduct a spatial and temporal analysis of the ecosystem service value (ESV) of the karst desertification control cycle (2015–2020). The results show that: 1) forest land, orchard land, and construction land increase, and dryland and grassland decrease. The landscape shows an aggregated state, with spreading and connectivity increasing while fragrant diversity is decreasing. 2) The total ecosystem service value increased by CNY 63.45 × 104, with regulating and cultural services on the rise and supply and support services on the decline. 3) With the rise of the TPI, the value of the supply services is inversely U-shaped, while the value of the remaining services increases. This study provides a case study about karst desertification areas for village-scale ecosystem services research.</p

Data_Sheet_1_Surgical resection for second primary colorectal cancer: a population-based study.DOCX

BackgroundSecond primary colorectal cancer (CRC) is attributed to a crucial component of the CRC population. Still, its treatments remain unclear due to the troublesome conditions originating from multiple primary cancers and the lack of quality evidence. This study aimed to determine that which type of surgical resection is the eligible treatment for second primary CRC among patients with a prior cancer history.MethodsThis cohort study retrospectively collected patients with second primary stage 0-III CRC in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Prevalence of surgical resection in second primary CRC, overall survival (OS) and disease-specific survival (DSS) of patients who received different surgical interventions were estimated.ResultsA total of 38,669 patients with second primary CRC were identified. Most of the patients (93.2%) underwent surgical resection as initial treatment. Approximately 39.2% of the second primary CRCs (N = 15,139) were removed with segmental resection, while 54.0% (N = 20,884) were removed through radical colectomy/proctectomy. Surgical resection was associated with a significantly favorable OS and DSS compared to those not receiving any surgical operations for second primary CRC [OS: adjusted Hazard ratios (adjusted HR): 0.35; 95% CI: 0.34–0.37, p ConclusionSurgical resection demonstrated excellent oncological superiority for second primary CRC and was used to remove the vast majority of second primary CRCs. In comparison to radical resection, segmental resection offered a better prognosis and reduced postoperative non-cancer complications. The second primary colorectal cancers should be resected if the patients can afford surgical operations.</p

Phosphine Catalyst-Controlled Cycloaddition or Dienylation Reactions of Trifluoromethyl Aryl Ketones with Bis-Substituted Allenoates

A chemoselective phosphine-catalyzed cycloaddition or dienylation reaction between trifluoromethyl-substituted ketones and bis-substituted allenoates was described. Under the catalysis of triarylphosphine, the reaction gave a range of trifluoromethylated tetrahydrofurans with broad substrate tolerance and good to excellent stereoselectivity, while the use of trialkylphosphine switched the reaction pathway to furnish CF₃-substituted dienyl tertiary alcohols chemoselectively. Moreover, a preliminary study on the asymmetric version of the reaction was also performed, which represents the first example of a phosphine-catalyzed asymmetric reaction between allenoates and carbonyl compounds

TIP30 and Endo B1 strongly bind phosphatidic acid.

<p>(<b>A</b>) Fatty acylation of endosomal lipids by the TIP30 complex. [³H]-arachidonic acid can be transferred to endosomal membrane lipids by the TIP30 complex, but not by TIP30M immunoprecipitates or control immunoprecipitates (left panel). The transfer was blocked by 10 µM triacsin C (right panel). Image was acquired by scanning lipids resolved on TLC plate with a Molecular Dynamics Storm 860. * indicates the radiolabeled lipid. (<b>B</b>) The schematic diagram shows the lipid species pre-spotted on membranes that are used in lipid-protein overlay assays. (<b>C</b>) TIP30 and Endo B1 strongly bind phosphatidic acid (PA). Protein-lipid overlay assays were carried out by incubating recombinant proteins with membrane strips containing 15 pre-spotted lipids. Membranes were scanned using a Li-Cor scanner after being sequentially overlaid with primary and fluorescent secondary antibodies.</p

Transmission electron microscopy analysis of products from in vitro vesicle fusion assays.

<p>(<b>A</b>) EGFR-DsRed and EYFP-Rab5a vesicles were incubated with immunopurified TIP30 complex in the fusion buffer with (right panel) or without (left panel) 100 nmol of arachidonic acid. Resulting vesicles were stained with uranyl acetate and examined using TEM. Scale bars, 500 nm. (<b>B</b>) The graphs show the percentages of vesicles with different diameters. At least 6 images from two independent experiments were counted. Data represent means ± SEM. n = 150; **<i>P</i><0.01, t test.</p