Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post‐myocardial infarction rats

Danqi soft capsule (DQ) is a traditional Chinese medicine containing Salvia miltiorrhiza and Panax notoginseng; it is safe and efficient in treating ischaemic heart diseases. The purpose of the present study was to assess whether DQ could prevent infarct border zone (IBZ) remodelling and decrease ventricular arrhythmias occurrence in post‐myocardial infarction (MI) stage. MI was induced by a ligation of the left anterior descending coronary artery. DQ was administered to the post‐MI rats started from 1 week after MI surgery for 4 weeks. The results showed that DQ treatment significantly attenuated tachyarrhythmia induction rates and arrhythmia score in post‐MI rats. In echocardiography, DQ improved left ventricular (LV) systolic and diastolic function. Histological assessment revealed that DQ significantly reduced fibrotic areas and myocyte areas, and increased connexin (Cx) 43 positive areas in IBZ. Western blot revealed that DQ treatment significantly reduced the protein expression levels of type I and III collagens, α‐smooth muscle actin (α‐SMA), transforming growth factor‐β1 (TGF‐β1) and Smad3 phosphorylation, while increasing Cx43 amounts. Overall, these findings mainly indicated that DQ intervention regulates interstitial fibrosis, Cx43 expression and myocyte hypertrophy by TGF‐β1/Smad3 pathway in IBZ, inhibits LV remodelling and reduces vulnerability to tachyarrhythmias after MI. This study presents a proof of concept for novel antiarrhythmic strategies in preventing IBZ remodelling, modifying the healed arrhythmogenic substrate and thus reducing susceptibility to ventricular arrhythmias in the late post‐MI period.     

RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway

Initial functional studies have demonstrated that RNA‐binding motif protein 10 (RBM10) can promote apoptosis and suppress cell proliferation; however, the results of several studies suggest a tumour‐promoting role for RBM10. Herein, we assessed the involvement of RBM10 in lung adenocarcinoma cell proliferation and explored the potential molecular mechanism. We found that, both in vitro and in vivo, RBM10 overexpression suppresses lung adenocarcinoma cell proliferation, while its knockdown enhances cell proliferation. Using complementary DNA microarray analysis, we previously found that RBM10 overexpression induces significant down‐regulation of RAP1A expression. In this study, we have confirmed that RBM10 decreases the activation of RAP1 and found that EPAC stimulation and inhibition can abolish the effects of RBM10 knockdown and overexpression, respectively, and regulate cell growth. This effect of RBM10 on proliferation was independent of the MAPK/ERK and P38/MAPK signalling pathways. We found that RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway.     

Long non‐coding RNA LINC01225 promotes proliferation,invasion and migration of gastric cancer via Wnt/β‐catenin signalling pathway

Emerging evidence has classified the aberrant expression of long non‐coding RNAs (lncRNAs) as a basic signature of various malignancies including gastric cancer (GC). LINC01225 has been shown to act as a hepatocellular carcinoma‐related gene, with its expression pattern and biological function not clarified in GC. Here, we verified that LINC01225 was up‐regulated in tumour tissues and plasma of GC. Analysis with clinicopathological information suggested that up‐regulation of LINC01225 was associated with advanced disease and poorer overall survival. Receiver operating characteristic (ROC) analysis showed that plasma LINC01225 had a moderate accuracy for diagnosis of GC. In addition, knockdown of LINC01225 led to retardation of cell proliferation, invasion and migration, and overexpression of LINC01225 showed the opposite effects. Mechanistic investigations showed that LINC01225 silencing inhibited epithelial‐mesenchymal transition (EMT) process and attenuated Wnt/β‐catenin signalling of GC. Furthermore, ectopic expression of Wnt1 or suppression of GSK‐3β abolished the si‐LINC01225‐mediated suppression against EMT, thereby promoting cell proliferation, invasion and migration of GC. In conclusion, LINC01225 promotes the progression of GC through Wnt/β‐catenin signalling pathway, and it may serve as a potential target or strategy for diagnosis or treatment of GC.     

Absence of estrogen receptor beta leads to abnormal adipogenesis during early tendon healing by an up‐regulation of PPARγ signalling

Achilles tendon injury is one of the challenges of sports medicine, the aetiology of which remains unknown. For a long time, estrogen receptor β (ERβ) has been known as a regulating factor of the metabolism in many connective tissues, such as bone, muscle and cartilage, but little is known about its role in tendon. Recent studies have implicated ERβ as involved in the process of tendon healing. Tendon‐derived stem cells (TDSCs) are getting more and more attention in tendon physiological and pathological process. In this study, we investigated how ERβ played a role in Achilles tendon healing. Achilles tendon injury model was established to analyse how ERβ affected on healing process in vivo. Cell proliferation assay, Western blots, qRT‐PCR and immunocytochemistry were performed to investigate the effect of ERβ on TDSCs. Here, we showed that ERβ deletion in mice resulted in inferior gross appearance, histological scores and, most importantly, increased accumulation of adipocytes during the early tendon healing which involved activation of peroxisome proliferator‐activated receptor γ (PPARγ) signalling. Furthermore, in vitro results of ours confirmed that the abnormity might be the result of abnormal TDSC adipogenic differentiation which could be partially reversed by the treatment of ERβ agonist LY3201. These data revealed a role of ERβ in Achilles tendon healing for the first time, thereby providing a new target for clinical treatment of Achilles tendon injury.     

One‐Step Controllable Synthesis of Catalytic Ni4Mo/MoOx/Cu Nanointerfaces for Highly Efficient Water Reduction

Currently, in addition to the electroactive non‐noble metal water‐splitting electrocatalysts, a scalable synthetic route and simple activity enhancement strategy is also urgently needed. In particular, the well‐controlled synthesis of the well‐recognized metal–metal nanointer face in a single step remains a key challenge. Here, the synthesis of Cu‐supported Ni₄Mo nanodots on MoO_x nanosheets (Ni₄Mo/MoO_x) with controllable Ni₄Mo particle size and d‐band structure is reported via a facile one‐step electrodeposition process. Density functional theory (DFT) calculations reveal that the active open‐shell effect from Ni‐3d‐band optimizes the electronic configuration. The Cu‐substrate enables the surface Ni–Mo alloy dots to be more electron‐rich, forming a local connected electron‐rich network, which boosts the charge transfer for effective binding of O‐related species and proton–electron charge exchange in the hydrogen evolution reaction. The Cu‐supported Ni₄Mo/MoO_x shows an ultralow overpotential of 16 mV at a current density of 10 mA cm^?2 in 1 m KOH, demonstrating the smallest overpotential, at loadings as low as 0.27 mg cm^?2, among all non‐noble metal catalysts reported to date. Moreover, an overpotential of 105 mV allows it to achieve a current density of 250 mA cm^?2 in 70 °C 30% KOH, a remarkable performance for alkaline hydrogen evolution with competitive potential for applications.     

Cytotoxic Spliceostatin Analogs from Pseudomonas sp.

Two new spliceostatin analogs, designed as spliceostatins J and K ( 1 and 2 ), were isolated and identified from the culture of Pseudomonas sp., along with two known ones, FR901464 ( 3 ) and spliceostatin E ( 4 ). Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D‐NMR and HR‐ESI‐MS. Spliceostatin J ( 1 ) represented the first example of spliceostatins bearing an unusual hexahydrofuro[3,4‐b]furan moiety. Biological assay showed all the isolated compounds except 1 displayed potent cytotoxic activities against two cancer cell lines (MDA‐MB‐231 and A‐549). Structure‐activity‐relationship studies revealed that the tetrahydropyran ring in spliceostatin analogs was necessary for their bioactive retention.     

A Desolvated Solid–Solid Interface for a High‐Capacitance Electric Double Layer

Understanding the electric double layer is essential for achieving efficient electrochemical energy storage technologies. A conventional solid–liquid electrode interface suffers from serious self‐discharge and a narrow voltage window, which makes the development of a solid–solid interface imperative. However, an in‐depth understanding of the electric double layer with a solid–solid interface is lacking. Here, a solid–solid interfacial electric double layer is proposed with excellent electrochemical performance. The solid layer is constructed by the electrochemical decomposition of lithium difluoro(oxalate)borate, which provides a desolvated environment for the establishment of a electric double layer. This makes a stronger interaction between the electrode surface and the ions. Based on this unique property, it is found that the solid–solid interfacial electric double layer has an increased capacitance, which suggests a way to develop high‐energy electrochemical capacitors.     

New Immunomodulating Polyhydroxypregnane Glycosides from the Roots of Cynanchum otophyllum C.K.Schneid.

Seven new polyhydroxypregnane glycosides, named cynotophyllosides P–V, together with three known analogs were isolated from the roots of Cynanchum otophyllum C.K.Schneid . Their structures were elucidated by a variety of spectroscopic techniques, as well as acid‐catalyzed hydrolysis. All isolates were tested for their immunological activities in vitro against Con A‐ and LPS‐induced proliferation of mice splenocytes. Immunoenhancing (for 1 , 9 ) and immunosuppressive (for 2 ) activities were observed. Furthermore, cynotophylloside R ( 3 ) showed immunomodulatory as it enhanced the proliferation of splenocytes in low concentration and suppressed immune cells in concentration more than 1.0 μg/ml.     

Biphenyl Derivatives from the Aerial Parts of Oenanthe javanica and Their COX‐2 Inhibitory Activities

Four new biphenyl derivatives ( 1 – 4 ), along with six known biphenyl derivatives ( 5 – 10 ) were isolated and elucidated by their detailed analyses of spectroscopic data and references from the aerial parts of Oenanthe javanica for the first time. Compounds ( 1 – 10 ) were assayed for their activities about the inhibition of COX‐2 enzyme in vitro for the first time. Compounds 1 , 2 , 4 , and 6 showed inhibitory activities against COX‐2 with IC₅₀ values ranging from 22.18±0.29 to 108.54±0.42 μm .