Photochemical Nickel-Catalyzed Reductive Migratory Cross-Coupling of Alkyl Bromides with Aryl Bromides

A novel method to access 1,1-diarylalkanes from readily available, nonactivated alkyl bromides and aryl bromides via visible-light-driven nickel and iridium dual catalysis, wherein diisopropylamine (^<i>i</i>Pr₂NH) is used as the terminal stoichiometric reductant, is reported. Both primary and secondary alkyl bromides can be successfully transformed into the migratory benzylic arylation products with good selectivity. Additionally, this method showcases tolerance toward a wide array of functional groups and the presence of bases

Accurate and Efficient Calculation of Protein–Protein Binding Free Energy-Interaction Entropy with Residue Type-Specific Dielectric Constants

Accurate and efficient computation of protein–protein binding free energy remains a grand challenge. In this study, we develop a new strategy to achieve efficient calculation for total protein–protein binding free energies with improved accuracy. The new method combines the recently developed interaction entropy method for efficient computation of entropic change together with the use of residue type-specific dielectric constants in the framework of MM/GBSA to achieve optimal result for protein–protein binding free energies. The new strategy is shown to be computationally efficient and accurate than that using standard MM/GBSA methods in which the entropic computation is performed by the normal model approach and the protein interior is represented by the standard dielectric constant (typically set to 1), both in terms of accuracy and computational efficiency. Our study using the new strategy on a set of randomly selected 20 protein–protein binding systems produced an optimal dielectric constant of 2.7 for charged residues and 1.1 for noncharged residues. Using this new strategy, the mean absolute error in computed binding free energies for these 20 selected protein–protein systems is significantly reduced by more than 3-fold while the computational cost is reduced by more than 2 orders of magnitude, compared to the result using standard MM/GBSA method with the normal mode approach. A similar improvement in accuracy is confirmed for a test set consisting of 10 protein–protein systems

Residue-specific free energy analysis in ligand bindings to JAK2

<p>Janus kinase 2 (JAK2) has vital importance on the regulation of proliferation, survival and differentiation of a variety of cells by the activation of JAK-STAT pathway. In this study, we employ a new approach to quantitatively calculate residue-specific binding free energies to identify hot-spots in ligand bindings to JAK2 using computational alanine scanning technique combined with the interaction entropy method for entropic change in binding free energies. This combined approach allows one to quantitatively analyse important protein–ligand binding interactions, and in addition, provides a new method for more accurate computation of total protein–ligand binding free energy. In this report, we computed a total of 14 JAK2–ligand binding systems, all with crystal structures and experimentally measured binding data. Key residues are identified with L983 being the quantitatively dominant residue in binding free energy contributions to the ligands. The values of the computed total JAK2–ligand binding free energies are in much closer agreement with experimentally measured data than those obtained by using the standard MM/GBSA approach. Our study thus provided new insights into specific binding mechanisms in ligand binding to JAK2.</p

Effects of endophytic and ectomycorrhizal basidiomycetes on <i>Quercus virginiana</i> seedling growth and nutrient absorption

Quercus virginiana (Fagaceae), native to the southeastern United States, has recently been introduced to the Yangtze Delta (China) and is often planted in landscaping and in coastal shelter forests. Here, we performed pot inoculation assays to evaluate the effects of two types of basidiomycetous root fungal symbionts, across four orders, on the growth and nutrient absorption of Q. virginiana seedlings. The results indicated that two isolates showed plant growth-promoting activities 2 months after inoculation. In particular, the ectomycorrhizal Sistotrema sp. (Cantharellales) had a pronounced effect on root development and morphology. With regard to nutrient absorption, the total nitrogen content in aboveground tissues was improved in inoculated seedlings, although most differences were not significant. Meanwhile, the total phosphorus contents in seedlings were either positively or negatively affected, probably depending on the symbiont type. Interestingly, the total potassium content in stems and leaves was significantly enhanced in all treatment groups. In addition, indole-3-acetic acid and abscisic acid production were determined in Sistotrema sp. and Atractiella rhizophila (Pucciniomycotina) by high-performance liquid chromatography tandem mass spectrometry. Our findings suggest that both endophytic and ectomycorrhizal fungi have beneficial effects on Q. virginiana growth, and highlight the potential for the development of mycobiome-based seedling raising techniques.</p

Table_2_Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.XLSX

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.</p

Data_Sheet_1_Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.PDF

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.</p

Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling of terminal alkenes with nonactivated alkyl halides. The success of this asymmetric reaction is ascribed to the application of a chiral anionic bisoxazoline ligand. This study provides a three-component strategy to access α- and β-stereogenic boronic esters from easily accessible starting materials. This protocol is characterized by mild reaction conditions, wide substrate scope and high regio- and enantioselectivity. We also showcase the value of this method in simplifying the synthesis of several drug molecules. Mechanistic studies suggest that the generation of enantioenriched boronic esters bearing an α-stereogenic center results from a stereoconvergent process, while the enantioselectivity-controlling step in the generation of boronic esters with a β-stereocenter is switched to the olefin migratory insertion step due to coordination of an ester group

Data_Sheet_4_Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.PDF

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.</p

Additional file 1 of Sodium-glucose cotransporter 2 inhibitor may not prevent atrial fibrillation in patients with heart failure: a systematic review

Supplemental Figure 1. Summary of risk of bias across all included studies. Supplemental Figure 2. Removing studies one by one in sensitivity analysis (a) Removing studies one by one in sensitivity analyse for all trails; (b) trails used empagliflozin; (c) trails follow-up time > 1 year. Supplemental Figure 3. Removing EMPEROR-Preserved in empagliflozin group M-H = Mantel-Haenszel; CI = confidence interval. Supplemental Table 1. PRISMA checklist. Supplemental Table 2. Harbord tes

Table_1_Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.XLSX

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.</p