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

Impact of AlphaFold on Structure Prediction of Protein Complexes: The CASP15-CAPRI Experiment

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homo-dimers, 3 homo-trimers, 13 hetero-dimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their 5 best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% for the targets compared to 8% two years earlier, a remarkable improvement resulting from the wide use of the AlphaFold2 and AlphaFold-Multimer software. Creative use was made of the deep learning inference engines affording the sampling of a much larger number of models and enriching the multiple sequence alignments with sequences from various sources. Wide use was also made of the AlphaFold confidence metrics to rank models, permitting top performing groups to exceed the results of the public AlphaFold-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem

Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem

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

Separation of Chloride and Sulfate Ions from Desulfurization Wastewater Using Monovalent Anions Selective Electrodialysis

The high concentration of chloride ions in desulphurization wastewater is the primary limiting factor for its reusability. Monovalent anion selective electrodialysis (S-ED) enables the selective removal of chloride ions, thereby facilitating the reuse of desulfurization wastewater. In this study, different concentrations of NaCl and Na2SO4 were used to simulate different softened desulfurization wastewater. The effects of current density and NaCl and Na2SO4 concentration on ion flux, permselectivity (PSO42−Cl−) and specific energy consumption were studied. The results show that Selemion ASA membrane exhibits excellent permselectivity for Cl− and SO42−, with a significantly lower flux observed for SO42− compared to Cl−. Current density exerts a significant influence on ion flux; as the current density increases, the flux of SO42− also increases but at a lower rate than that of Cl−, resulting in an increase in permselectivity. When the current density reaches 25 mA/cm2, the permselectivity reaches a maximum of 50.4. The increase in NaCl concentration leads to a decrease in the SO42− flux; however, the permselectivity is reduced due to the elevated Cl−/SO42− ratio. The SO42− flux increases with the increase in Na2SO4 concentration, while the permselectivity increases with the decrease in Cl−/SO42− ratio

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