Increased expression of pigment epithelium-derived factor in aged mesenchymal stem cells impairs their therapeutic efficacy for attenuating myocardial infarction injury.

AIMS: Mesenchymal stem cells (MSCs) can ameliorate myocardial infarction (MI) injury. However, older-donor MSCs seem less efficacious than those from younger donors, and the contributing underlying mechanisms remain unknown. Here, we determine how age-related expression of pigment epithelium-derived factor (PEDF) affects MSC therapeutic efficacy for MI. METHODS AND RESULTS: Reverse transcriptase-polymerized chain reaction and enzyme-linked immunosorbent assay analyses revealed dramatically increased PEDF expression in MSCs from old mice compared to young mice. Morphological and functional experiments demonstrated significantly impaired old MSC therapeutic efficacy compared with young MSCs in treatment of mice subjected to MI. Immunofluorescent staining demonstrated that administration of old MSCs compared with young MSCs resulted in an infarct region containing fewer endothelial cells, vascular smooth muscle cells, and macrophages, but more fibroblasts. Pigment epithelium-derived factor overexpression in young MSCs impaired the beneficial effects against MI injury, and induced cellular profile changes in the infarct region similar to administration of old MSCs. Knocking down PEDF expression in old MSCs improved MSC therapeutic efficacy, and induced a cellular profile similar to young MSCs administration. Studies in vitro showed that PEDF secreted by MSCs regulated the proliferation and migration of cardiac fibroblasts. CONCLUSIONS: This is the first evidence that paracrine factor PEDF plays critical role in the regulatory effects of MSCs against MI injury. Furthermore, the impaired therapeutic ability of aged MSCs is predominantly caused by increased PEDF secretion. These findings indicate PEDF as a promising novel genetic modification target for improving aged MSC therapeutic efficacy

The Lunar Lander Neutron and Dosimetry (LND) Experiment on Chang'E 4

Chang'E 4 is the first mission to the far side of the Moon and consists of a lander, a rover, and a relay spacecraft. Lander and rover were launched at 18:23 UTC on December 7, 2018 and landed in the von K\'arm\'an crater at 02:26 UTC on January 3, 2019. Here we describe the Lunar Lander Neutron \& Dosimetry experiment (LND) which is part of the Chang'E 4 Lander scientific payload. Its chief scientific goal is to obtain first active dosimetric measurements on the surface of the Moon. LND also provides observations of fast neutrons which are a result of the interaction of high-energy particle radiation with the lunar regolith and of their thermalized counterpart, thermal neutrons, which are a sensitive indicator of subsurface water content.Comment: 38 pages, submitted to Space Science Review

A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification

Alkali-Etched NiCoAl-LDH with Improved Electrochemical Performance for Asymmetric Supercapacitors

Hydrotalcite, first found in natural ores, has important applications in supercapacitors. NiCoAl-LDH, as a hydrotalcite-like compound with good crystallinity, is commonly synthesized by a hydrothermal method. Al3+ plays an important role in the crystallization of hydrotalcite and can provide stable trivalent cations, which is conducive to the formation of hydrotalcite. However, aluminum and its hydroxides are unstable in a strong alkaline electrolyte; therefore, a secondary alkali treatment is proposed in this work to produce cation vacancies. The hydrophilicity of the NiCoAl-OH surface with cation vacancy has been greatly improved, which is conducive to the wetting and infiltration of electrolyte in water-based supercapacitors. At the same time, cation vacancies generate a large number of defects as active sites for energy storage. As a result, the specific capacity of the NiCoAl-OH electrode after 10,000 cycles can be maintained at 94.1%, which is much better than the NiCoAl-LDH material of 74%

Improving obesity and lipid metabolism using conjugated linoleic acid

Abstract Background Conjugated linoleic acid (CLA) can prevent fatty acid accumulation induced by a high‐fructose diet and improve lipid metabolism disorders in patients. Objectives We aimed to investigate the effect of CLA on obesity and lipid metabolism and its possible mechanism. Methods Eight‐month‐old male BKS.Cg‐Dock7m +/+ Leprdb/JNju (db/db) mice (n = 12) were fed a CLA mix composed of equivalent c9, t11‐CLA and t10, c12‐CLA for 1 month. The effect of CLA on body weight, water and food intake, and triglyceride (TG) and total cholesterol (TC) levels was investigated. PPARα, PPARγ and CD36 expression was determined by quantitative PCR and western blotting. Additionally, the expression of these three genes was studied in HepG2 cells treated with CLA and linoleic acid. Results CLA treatment notably reduced the dietary and water intake of db/db mice, effectively reduced body weight, and decreased serum TG and TC levels (p < 0.05). Increased expression of PPARα (p < 0.05) and decreased expression of CD36 (p < 0.001) were observed in the liver of mice that were fed CLA. CLA increased PPARα expression (p < 0.001) and decreased PPARγ (p < 0.001) and CD36 expression (p < 0.01) in HepG2 cells. Conclusions Our results showed that CLA can improve lipid metabolism in obese mice through upregulation of PPARα expression and downregulation of CD36 expression

Prediction of Failure Modes and Minimum Characteristic Value of Transverse Reinforcement of RC Beams Based on Interpretable Machine Learning

Shear failure of reinforced concrete (RC) beams is a form of brittle failure and has always been a concern. This study adopted the interpretable machine-learning technique to predict failure modes and identify the boundary value between different failure modes to avoid diagonal splitting failure. An experimental database consisting of 295 RC beams with or without transverse reinforcements was established. Two features were constructed to reflect the design characteristics of RC beams, namely, the shear&ndash;span ratio and the characteristic value of transverse reinforcement. The characteristic value of transverse reinforcement has two forms: (i) &lambda;sv,ft=&rho;stpfsv/ft, from the China design code of GB 50010-2010; and (ii) &lambda;sv,fc&prime;=&rho;stpfsv/fc&prime;0.5, from the America design code of ACI 318-19 and Canada design code of CSA A23.3-14. Six machine-learning models were developed to predict failure modes, and gradient boosting decision tree and extreme gradient boosting are recommended after comparing the prediction performance. Then, shapley additive explanations (SHAP) indicates that the characteristic value of transverse reinforcement has the most significant effect on failure mode, follow by the shear&ndash;span ratio. The characteristic value of transverse reinforcement is selected as the form of boundary value. On this basis, an accumulated local effects (ALE) plot describes how this feature affects model prediction and gives the boundary value through numerical simulation, that is, the minimum characteristic value of transverse reinforcement. Compared with the three codes, the suggested value for &lambda;sv,fc&prime;,min has higher reliability and security for avoiding diagonal splitting failure. Accordingly, the research approach in this case is feasible and effective, and can be recommended to solve similar tasks