Protective effect of phospholipids in lipoproteins against diabetic kidney disease: A Mendelian randomization analysis.

BACKGROUND: The etiology of diabetic kidney disease is complex, and the role of lipoproteins and their lipid components in the development of the disease cannot be ignored. However, phospholipids are an essential component, and no Mendelian randomization studies have yet been conducted to examine potential causal associations between phospholipids and diabetic kidney disease. METHODS: Relevant exposure and outcome datasets were obtained through the GWAS public database. The exposure datasets included various phospholipids, including those in LDL, IDL, VLDL, and HDL. IVW methods were the primary analytical approach. The accuracy of the results was validated by conducting heterogeneity, MR pleiotropy, and F-statistic tests. MR-PRESSO analysis was utilized to identify and exclude outliers. RESULTS: Phospholipids in intermediate-density lipoprotein (OR: 0.8439; 95% CI: 0.7268-0.9798), phospholipids in large low- density lipoprotein (OR: 0.7913; 95% CI: 0.6703-0.9341), phospholipids in low- density lipoprotein (after removing outliers, OR: 0.788; 95% CI: 0.6698-0.9271), phospholipids in medium low- density lipoprotein (OR: 0.7682; 95% CI: 0.634-0.931), and phospholipids in small low-density lipoprotein (after removing outliers, OR: 0.8044; 95% CI: 0.6952-0.9309) were found to be protective factors. CONCLUSIONS: This study found that a higher proportion of phospholipids in intermediate-density lipoprotein and the various subfractions of low-density lipoprotein, including large LDL, medium LDL, and small LDL, is associated with a lower risk of developing diabetic kidney disease.

Whitening and antioxidant activities of Inonotus sanghuang Extract and development of primary whitening gel products.

Polysaccharides and flavonoids have excellent antioxidant properties and tyrosinase inhibitory effects. In this paper, the antioxidant capacity of Inonotus sanghuang extract and its inhibition kinetics on mushroom tyrosinase were investigated to determine the preparation process of Inonotus sanghuang primary whitening gel. By conducting experimental studies on the effects of water extract and alcohol extract of Inonotus sanghuang on antioxidant capacity and tyrosinase activity, their inhibitory ability and types of inhibitory effects were determined. The single factor experiment was used to determine the preparation process of Sanghuang primary whitening gel. This study has proven that the extract of Inonotus sanghuang possesses antioxidant and tyrosinase inhibitory capabilities. It also identified the preparation process for the primary whitening gel of Inonotus sanghuang, thereby providing a theoretical and experimental basis for the development of whitening products utilising Inonotus sanghuang.

[Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats].

Objective: To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. Methods: A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). Results: CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Conclusion: Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

Using 7.0 T cardiac magnetic resonance to investigate the effect of estradiol on biventricular structure and function of ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

BACKGROUND: Despite that estradiol can reduce the risk of cardiovascular diseases in ovariectomized animals in the plains, its effect on animals at high altitude has seldom been reported. We hypothesize that estradiol can ameliorate cardiac damage to ovariectomized rats induced by chronic exposure to hypobaric hypoxia at high altitude. PURPOSE: This study was intended to investigate whether cardiovascular magnetic resonance (CMR) imaging could reveal cardioprotective effect of estradiol on ovariectomized rats under chronic exposure to hypobaric hypoxia at high altitude. METHODS: Thirty-two rats were randomized into the Control group (Plain), HH + Sham group (Hypobaric Hypoxia + Sham), HH + OVX group (Hypobaric Hypoxia + Bilateral Ovariectomy) and HH-OVX + E2 group (Hypobaric Hypoxia + Bilateral Ovariectomy + Estradiol, 50 µg/kg, 3 times a week, for 6 weeks) (n = 8 per group). Except the Control group (altitude: 500 m), rats in other groups were subcutaneously injected with 17ß -estradiol or vehicle and exposed to chronic hypobaric hypoxia in Qinghai-Tibet Plateau (altitude: 4250 m), China, for 6 weeks. Biventricular cardiac function and global strain of the rats were measured by CMR and analyzed using the cine tissue tracking techniques. Biochemical tests, histopathology and electronic microscopy were used to evaluate the protective effect of estradiol on the heart tissue of ovariectomized rats exposed to a high-altitude environment. RESULTS: The biventricular ejection fraction and global strains decreased in the HH + OVX group compared with that in the Control group (all p < 0.05). All the aforementioned changes in the HH + OVX group ameliorated in the HH-OVX + E2 group (all p < 0.05). Estradiol also alleviated the right ventricular dilatation and hypertrophy in the HH + OVX group (all p < 0.05). In addition, histological and biochemical analyses also supported these in vivo results. CONCLUSIONS: Estradiol ameliorated the biventricular structural and functional damage in ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

A Density Functional Tight Binding Layer for Deep Learning of Chemical Hamiltonians.

Current neural networks for predictions of molecular properties use quantum chemistry only as a source of training data. This paper explores models that use quantum chemistry as an integral part of the prediction process. This is done by implementing self-consistent-charge Density-Functional-Tight-Binding (DFTB) theory as a layer for use in deep learning models. The DFTB layer takes, as input, Hamiltonian matrix elements generated from earlier layers and produces, as output, electronic properties from self-consistent field solutions of the corresponding DFTB Hamiltonian. Backpropagation enables efficient training of the model to target electronic properties. Two types of input to the DFTB layer are explored, splines and feed-forward neural networks. Because overfitting can cause models trained on smaller molecules to perform poorly on larger molecules, regularizations are applied that penalize nonmonotonic behavior and deviation of the Hamiltonian matrix elements from those of the published DFTB model used to initialize the model. The approach is evaluated on 15 700 hydrocarbons by comparing the root-mean-square error in energy and dipole moment, on test molecules with eight heavy atoms, to the error from the initial DFTB model. When trained on molecules with up to seven heavy atoms, the spline model reduces the test error in energy by 60% and in dipole moments by 42%. The neural network model performs somewhat better, with error reductions of 67% and 59%, respectively. Training on molecules with up to four heavy atoms reduces performance, with both the spline and neural net models reducing the test error in energy by about 53% and in dipole by about 25%.

A Least-Squares Commutator in the Iterative Subspace Method for Accelerating Self-Consistent Field Convergence.

A least-squares commutator in the iterative subspace (LCIIS) approach is explored for accelerating self-consistent field (SCF) calculations. LCIIS is similar to direct inversion of the iterative subspace (DIIS) methods in that the next iterate of the density matrix is obtained as a linear combination of past iterates. However, whereas DIIS methods find the linear combination by minimizing a sum of error vectors, LCIIS minimizes the Frobenius norm of the commutator between the density matrix and the Fock matrix. This minimization leads to a quartic problem that can be solved iteratively through a constrained Newton's method. The relationship between LCIIS and DIIS is discussed. Numerical experiments suggest that LCIIS leads to faster convergence than other SCF convergence accelerating methods in a statistically significant sense, and in a number of cases LCIIS leads to stable SCF solutions that are not found by other methods. The computational cost involved in solving the quartic minimization problem is small compared to the typical cost of SCF iterations and the approach is easily integrated into existing codes. LCIIS can therefore serve as a powerful addition to SCF convergence accelerating methods in computational quantum chemistry packages.

Total synthesis of thaxtomin A and its stereoisomers and findings of their biological activities.

The first and facile total synthesis of thaxtomin A and its three stereoisomers has been achieved. The synthetic approach involves intramolecular nucleophilic cyclization of an amide toward a ketoamide group to produce a C-hydroxydiketopiperazine scaffold. The most amazing discovery was that each of the four stereoisomers of TA exhibits different phytotoxic, fungicidal, and antiviral activities.