Potential Underestimation of Left Ventricular Mechanical Dyssynchrony in Dyssynchrony and Outcomes Assessment.

Objective: Left ventricular (LV) mechanical dyssynchrony (LVMD) is fundamental to the progression of heart failure and ventricular remodeling. The status of LVMD in different patterns of bundle branch blocks (BBB) is unclear. In this study, we analyzed the relationship between LVMD and left ventricular systolic dysfunction using real-time three-dimensional echocardiography (RT-3DE). Methods: RT-3DE and conventional two-dimensional echocardiography were performed on 68 patients with left bundle branch block (LBBB group), 106 patients with right bundle branch block (RBBB group), and 103 patients without BBB (Normal group). The RT-3DE data sets provided time-volume analysis for global and segmental LV volumes. The LV systolic dyssynchrony index (LVSDI) was calculated using the standard deviation (SD) and maximal difference (Dif) of time to minimum segmental volume (tmsv) for LV segments adjusted by the R-R interval. LVMD was considered if the LVSDI (Tmsv-16-SD) was greater than or equal to 5%. Results: LVSDI is negatively and significantly correlated with left ventricular ejection fraction (LVEF), but not with BBB or QRS duration. The proportion of LVMD in the LBBB, RBBB, and Normal group was 30.88%, 28.30%, and 25.24%, respectively, and there was no significant difference. Conclusion: In dilated cardiomyopathy, LVMD is more closely related to LVEF reduction than QRS morphology and duration.

Asymmetric 2,4-Dienylation/[4 + 2] Annulation Cascade to Construct Fused Frameworks via Auto-Tandem Palladium Catalysis.

A palladium catalyzed tandem reaction between ortho-functionalized aryl enones and 2,4-dienyl carbonates has been presented, proceeding through sequential 2,4-dienylation/Michael addition/π-σ-π isomerization/allylic alkylation. A broad array of enantioenriched architectures having fused and spirocyclic frameworks are constructed in moderate to excellent yields and stereoselectivity. Notably, the intrinsic intramolecular Diels-Alder reaction pattern of the dienylated intermediates is well reversed via Pd(0)-π-Lewis base catalysis.

Chrysin improves diabetic nephropathy by regulating the AMPK-mediated lipid metabolism in HFD/STZ-induced DN mice.

Diabetic nephropathy (DN) is a highly prevalent and severe diabetic complication. It is urgent to explore high efficiency and minor side effects therapy for DN. Chrysin is a natural flavonoid with various biological activities found in honey and propolis, and has considerable potential to improve DN. The study was designed to explore the effects and the specific underlying mechanism of chrysin for DN in high-fat-diet (HFD) and streptozotocin (STZ) induced DN mice. Firstly, the study revealed that chrysin effectively improved obesity, insulin resistance (IR), renal function, and pathological injury in DN mice. Secondly, the study found that chrysin improved the key indices and markers of lipid accumulation, oxidative stress, and inflammation which are closely related to the development or progression of DN. Moreover, chrysin markedly modulated lipid metabolism by regulating Adenosine 5' monophosphate-activated protein kinase (AMPK) and essential downstream proteins. Furthermore, AMPK inhibitor (Dorsomorphin) intervention partially suppressed the positive effects of chrysin on all testing indicators, indicating that activated AMPK is crucial for chrysin action on DN. The present study demonstrated that chrysin may improve DN by regulating lipid metabolism, and activated AMPK plays a critical role in the regulation of chrysin. PRACTICAL APPLICATIONS: The study verified the positive effects of chrysin on obesity, insulin resistance, kidney injury, renal function, lipid accumulation, inflammation, and oxidative stress, which are closely related to the development or progression of diabetic nephropathy (DN). Moreover, we explored that chrysin improves DN by regulating AMPK-mediated lipid metabolism. Furthermore, the AMPK inhibitor was used to confirm that activated AMPK plays a critical role in the effects of chrysin. These results could offer a full explanation and a potential option for adjuvant therapy of DN diabetes with chrysin.

Major royal jelly proteins alleviate non-alcoholic fatty liver disease in mice model by regulating disordered metabolic pathways.

Nonalcoholic fatty liver disease (NAFLD), the major cause of global chronic hepatic injury, has obtained increasing attention while the current drug treatment still laid safety hazards. Major royal jelly proteins (MRJPs), the water-soluble proteins enriched in royal jelly (RJ), were applied to study its effects on improving NAFLD in the NAFLD mouse model. Herein, we demonstrated that intaking of 250-500 mg/kg/day MRJPs significantly decreased the rate of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. Next, TOF to MRM ("TM") widely targeted metabolomics (untargeted metabolomics + widely targeted metabolomics) was further used to explore the potential mechanism, and we found that 500 mg/kg MRJPs alleviated lipid metabolism, oxidative stress, and inflammation mainly by regulating the metabolisms of alpha-linolenic acid, linoleic acid, arachidonic acid, and biosynthesis of unsaturated fatty acids. Moreover, by detecting multiple oxidative stress factors and inflammatory cytokines, we found that MRJPs indeed exerted antioxidant and anti-inflammatory effects. Together, we demonstrated that MRJPs could mediate the progress of NAFLD through the "multi-component-multi-target-multi-pathway" mechanism, which could be considered as an ideal functional food in alleviating NAFLD. PRACTICAL APPLICATIONS: Royal jelly (RJ) is a bee product with high nutritional value. Major royal jelly proteins (MRJPs) are water-soluble proteins in RJ. Our research showed that MRJPs significantly ameliorated NAFLD induced by a high-fat diet in mice, suggesting that MRJPs could be used as an active ingredient to help improve NAFLD, which was beneficial for the development of related functional foods and the economic value of RJ. Moreover, the metabolic pathways involved in the ameliorative effect of MRJPs were investigated, which provided new ideas for the prevention and treatment of NAFLD.

Asymmetric Auto-Tandem Palladium Catalysis for 2,4-Dienyl Carbonates: Ligand-Controlled Divergent Synthesis.

Developing new asymmetric auto-tandem catalysis processes, especially in a divergent manner, is highly attractive but extremely challenging. Presented herein is a palladium-catalyzed auto-tandem reaction between 2,4-dienyl carbonates and o-TsNH arylimines or trifluoroacetophenones that proceeds through a consecutive N-allylation, vinylogous addition, π-σ-π isomerization, and another N-allylation sequence. Importantly, switchable diastereodivergent synthesis could be achieved by tuning the chiral bisphosphine ligands, which led to the construction of a broad spectrum of fused tetrahydroquinoline architectures with moderate to excellent enantioselectivity. Ligand control even enabled effective access to regiodivergent azetidine or chemodivergent ß-H elimination with fair enantioselectivity, further showing the versatility of the current auto-tandem catalysis.

A Palladium Complex as an Asymmetric π-Lewis Base Catalyst for Activating 1,3-Dienes.

Here we report that palladium(0) complexes can coordinate in a η2 fashion to 1,3-dienes and significantly raise the energy of their highest occupied molecular orbital (HOMO) by donating the electrons from the d-orbitals to the empty antibonding molecular orbitals of double bonds (π*) via back-bonding. Thus, the uncoordinated double bond, as a more reactive partner on the basis of the principle of vinylogy, can directly attack imines, furnishing a formal hydrodienylation reaction enantioselectively. A chemoselective cascade vinylogous addition/allylic alkylation difunctionalization process between 1,3-dienes and imines with a nucleophilic group is also compatible, by trapping in situ formed π-allylpalladium species after initial ene addition. This π-Lewis base catalytic mode, featuring simple η2coordination, vinylogous activation, and compatibility with both conjugated neutral polyenes and electron-deficient polyenes, is elucidated by control experiments and density functional theory (DFT) calculations.