Association of suboptimal health status with intestinal microbiota in Chinese youths

Suboptimal health status (SHS), a physical state between health and disease, is a subclinical and reversible stage of chronic disease. Previous studies have shown alterations in the intestinal microbiota in patients with some chronic diseases. This study aimed to investigate the association between SHS and intestinal microbiota in a case‐control study with 50 SHS individuals and 50 matched healthy controls. Intestinal microbiota was analysed by MiSeq 250PE. Alpha diversity of intestinal microbiota in SHS individuals was higher compared with that of healthy controls (Simpson index, W = 2238, P = .048). Beta diversity was different between SHS and healthy controls (P = .018). At the phylum level, the relative abundance of Verrucomicrobia was higher in the SHS group than that in the controls (W = 2201, P = .049). Compared with that of the control group, nine genera were significantly higher and five genera were lower in abundance in the SHS group (all P < .05). The intestinal microbiota, analysed by a random forest model, was able to distinguish individuals with SHS from the controls, with an area under the curve of 0.79 (95% confidence interval: 0.77‐0.81). We demonstrated that the alteration of intestinal microbiota occurs with SHS, an early stage of disease, which might shed light on the importance of intestinal microbiota in the primary prevention of noncommunicable chronic diseases.     

Reduction of SOST gene promotes bone formation through the Wnt/β-catenin signalling pathway and compensates particle-induced osteolysis

The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO-Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase- (ALP) and osterix-positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3-E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased β-catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased β-catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/β-catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis.     

Loganin alleviates testicular damage and germ cell apoptosis induced by AGEs upon diabetes mellitus by suppressing the RAGE/p38MAPK/NF-κB pathway

Diabetes mellitus (DM) damages male reproduction at multiple levels, such as endocrine secretion, spermatogenesis and penile erection. We herein investigated the protective effects and mechanism of loganin targeting the advanced glycation end products (AGEs)/receptor for AGEs (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/NF-κB signalling pathway. Loganin relieved the general DM symptoms and decreased the blood glucose level of KK-Ay DM mice. Haematoxylin-eosin staining demonstrated that loganin ameliorated testicular histology and function and enhanced the activities of testis-specific markers lactate dehydrogenase (LDH), acid phosphatase (ACP) and gamma-glutamyl transferase (γ-GT). Loganin also showed evident anti-oxidative stress, anti-apoptotic and anti-inflammatory effects on DM-induced reproductive damage by restoring glutathione (GSH) level and superoxide dismutase (SOD) activity, as well as reducing reactive oxygen species (ROS) level and Bax/Bcl-2 ratio in vivo and in vitro. Western blotting exhibited that loganin significantly inhibited the AGEs/RAGE/p38MAPK/NF-κB signalling pathway. Acridine orange and ethidium bromide staining (AOEB) and Western blotting showed that loganin in combination with inhibitors of RAGE, p38MAPK and NF-κB exerted stronger anti-apoptotic effects on AGE-induced GC-2 cell damage compared with loganin alone. In conclusion, loganin can protect against DM-induced reproductive damage, probably by suppressing the AGEs/RAGE/p38MAPK/NF-κB pathway.     

ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARα/LDHB/ERK‐glycolysis signalling axis

Acute myeloid leukaemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. 4‐Amino‐2‐trifluoromethyl‐phenyl retinate (ATPR), a novel all‐trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show superior anticancer effect compared with ATRA on various cancers. However, its potential effect on AML remains largely unknown. Lactate dehydrogenase B (LDHB) is the key glycolytic enzyme that catalyses the interconversion between pyruvate and lactate. Currently, little is known about the role of LDHB in AML. In this study, we found that ATPR showed antileukaemic effects with RARα dependent in AML cells. LDHB was aberrantly overexpressed in human AML peripheral blood mononuclear cell (PBMC) and AML cell lines. A lentiviral vector expressing LDHB‐targeting shRNA was constructed to generate a stable AML cells with low expression of LDHB. The effect of LDHB knockdown on differentiation and cycle arrest of AML cells was assessed in vitro and vivo, including involvement of Raf/MEK/ERK signalling. Finally, these data suggested that ATPR showed antileukaemic effects by RARα/LDHB/ ERK‐glycolysis signalling axis. Further studies should focus on the underlying leukaemia‐promoting mechanisms and investigate LDHB as a therapeutic target.     

Cardioprotective effect of isorhamnetin against myocardial ischemia reperfusion (I/R) injury in isolated rat heart through attenuation of apoptosis

In this study, we investigated the effects of isorhamnetin on myocardial ischaemia reperfusion (I/R) injury in Langendorff-perfused rat hearts. Isorhamnetin treatment (5, 10 and 20 μg/mL) significantly alleviated cardiac morphological injury, reduced myocardial infarct size, decreased the levels of marker enzymes (LDH and CK) and improved the haemodynamic parameters, reflected by the elevated levels of the left ventricular developed pressure (LVDP), coronary flow (CF) and the maximum up/down velocity of left ventricular pressure (+dp/dt_max). Moreover, isorhamnetin reperfusion inhibited apoptosis of cardiomyocytes in the rats subjected to cardiac I/R in a dose-dependent manner concomitant with decreased protein expression of Bax and cleaved-caspase-3, as well as increased protein expression of Bcl-2. In addition, I/R-induced oxidative stress was manifestly mitigated by isorhamnetin treatment, as showed by the decreased malondialdehyde (MDA) level and increased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). These results indicated that isorhamnetin exerts a protective effect against I/R-induced myocardial injury through the attenuation of apoptosis and oxidative stress.     

Circulating exosome‐derived bona fide long non‐coding RNAs predicting the occurrence and metastasis of hepatocellular carcinoma

Although the diagnosis and therapy approach developed, techniques for the early diagnosis of HCC remain insufficient which results in poor prognosis of patients. The traditional biomarker AFP, however, has been proved with low specificity. Circulating exosomal ncRNAs revealed different profiles reflecting the characteristics of tumour. In this study, we mainly focused on circulating exosomal ncRNAs which might be the fingerprint for HCC, especially for the diagnosis or metastasis prediction. A high throughput lncRNA microarray in exosomes extracted from cell‐free plasma was applied. The risk score analysis was employed to screen the potential exosome‐derived lncRNAs in two independent sets based on different clinical parameters in 200 paired HCC patients. After a multi‐stage validation, we finally revealed three lncRNAs, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, increased in HCC comparing with the both chronic hepatitis (CH) patients and cancer‐free controls. ROC curve revealed a higher sensitivity and specificity in predicting the occurrence of HCC from cancer‐free controls and CH patients with the area under curve (AUC) of 0.905 and 0.879 by combining AFP. The three lncRNA panel combined with AFP also indicted a fingerprint function in predicting the metastasis of HCC with the AUC of 0.870. In conclusion, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2 might be the potential biomarker for the tumorigenesis prediction from CH patients or healthy controls and may also be applied for dynamic monitoring the metastasis of HCC.     

Efficient Organic Solar Cell with 16.88% Efficiency Enabled by Refined Acceptor Crystallization and Morphology with Improved Charge Transfer and Transport Properties

Single‐layered organic solar cells (OSCs) using nonfullerene acceptors have reached 16% efficiency. Such a breakthrough has inspired new sparks for the development of the next generation of OSC materials. In addition to the optimization of electronic structure, it is important to investigate the essential solid‐state structure that guides the high efficiency of bulk heterojunction blends, which provides insight in understanding how to pair an efficient donor–acceptor mixture and refine film morphology. In this study, a thorough analysis is executed to reveal morphology details, and the results demonstrate that Y6 can form a unique 2D packing with a polymer‐like conjugated backbone oriented normal to the substrate, controlled by the processing solvent and thermal annealing conditions. Such morphology provides improved carrier transport and ultrafast hole and electron transfer, leading to improved device performance, and the best optimized device shows a power conversion efficiency of 16.88% (16.4% certified). This work reveals the importance of film morphology and the mechanism by which it affects device performance. A full set of analytical methods and processing conditions are executed to achieve high efficiency solar cells from materials design to device optimization, which will be useful in future OSC technology development.     

Hollow CuS Nanoboxes as Li‐Free Cathode for High‐Rate and Long‐Life Lithium Metal Batteries

Transition metal sulfides hold promising potentials as Li‐free conversion‐type cathode materials for high energy density lithium metal batteries. However, the practical deployment of these materials is hampered by their poor rate capability and short cycling life. In this work, the authors take the advantage of hollow structure of CuS nanoboxes to accommodate the volume expansion and facilitate the ion diffusion during discharge–charge processes. As a result, the hollow CuS nanoboxes achieve excellent rate performance (≈371 mAh g^?1 at 20 C) and ultra‐long cycle life (>1000 cycles). The structure and valence evolution of the CuS nanobox cathode are identified by scanning electron microscopy, transmission electron microscopy, and X‐ray photoelectron spectroscopy. Furthermore, the lithium storage mechanism is revealed by galvanostatic intermittent titration technique and operando Raman spectroscopy for the initial charge–discharge process and the following reversible processes. These results suggest that the hollow CuS nanobox material is a promising candidate as a low‐cost Li‐free cathode material for high‐rate and long‐life lithium metal batteries.