Traditional Chinese medicine improves myasthenia gravis by regulating the symbiotic homeostasis of the intestinal microbiota and host

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies that is dependent on T-cell immunity and complement participation and mainly involves neuromuscular junctions. In this study, 30 patients with myasthenia gravis were selected and divided into pretreatment (Case group) and posttreatment (Treatment group) and 30 healthy volunteers (CON group) were included. Among them, the treatment group was treated with Modified Buzhong Yiqi Decoction (MBZYQD), and the levels of antibodies such as AChR, Musk and Titin in blood and intestinal microbiota were compared before treatment (Case group), after treatment (Treatment group) and in healthy volunteers (CON group). The results showed that after treatment with MBZYQD, the antibody levels of AChR, MuSK, and Titin and the inflammatory factor level of IL-6, IL-1β, and IL-22 in MG patients decreased significantly and nearly returned to a healthy level. In addition, after treatment with MBZYQD, the diversity, structure and function of intestinal microorganisms in MG patients also recovered to a healthy level. At the phylum level, the relative abundance of Proteobacteria in the Case group increased significantly, accompanied by a significant decrease in the relative abundance of Bacteroides compared with that in the CON group, the relative abundance of Proteobacteria and Bacteroides in the Treatment group was similar to that in the CON group. At the genus level, the relative abundance of Shigella in the Case group was significantly increased, accompanied by a significant decrease in the relative abundance of Prevotella, and the relative abundance of Shigella and Prevotella in Treatment group was similar to that in the CON group. Moreover, the fluorobenzoate degradation pathway (KO00364) was significantly increased in the Case group, while this pathway was significantly decreased in the Treatment group. In conclusion, MBZYQD can improve the immune function of the host by regulating the diversity, structure and function of the intestinal microbiota to treat myasthenia gravis

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

Recent Advances in and New Perspectives on Crystalline Silicon Solar Cells with Carrier-Selective Passivation Contacts

Crystalline silicon (c-Si) is the dominating photovoltaic technology today, with a global market share of about 90%. Therefore, it is crucial for further improving the performance of c-Si solar cells and reducing their cost. Since 2014, continuous breakthroughs have been achieved in the conversion efficiencies of c-Si solar cells, with a current record of 26.6%. The great efficiency boosts originate not only from the materials, including Si wafers, emitters, passivation layers, and other functional thin films, but also from novel device structures and an understanding of the physics of solar cells. Among these achievements, the carrier-selective passivation contacts are undoubtedly crucial. Current carrier-selective passivation contacts can be realized either by silicon-based thin films or by elemental and/or compound thin films with extreme work functions. The current research and development status, as well as the future trends of these passivation contact materials, structures, and corresponding high-efficiency c-Si solar cells will be summarized

Optimal Orientation and Tilt Angle for Maximizing in-Plane Solar Irradiation for PV Applications in Japan

To maximize the direct insolation received by flat-plate photovoltaic (PV) modules, the tilt angle is usually the site’s latitude and the modules are oriented towards the equator. However, this may not be the optimal placement, as the local climatic conditions will influence the optimal orientation and tilt angle. Transposition models can be used to simulate the insolation on planes with various tilts and azimuths, using a single set of (horizontal) global and diffuse irradiance measurements. Following this method, five maps including optimal orientations, tilt angles, maximum annual tilted irradiations, percentage improvements of the optimally-tilted PV installation versus the conventional latitude-tilted PV installation, and annual diffuse fraction were plotted over the geographical area of Japan. Spatial patterns in these maps were observed and analyzed. The key contribution of this work is to establish a database of optimal PV installations in Japan. Compared to the conventional rule of thumb of tilting the module at latitude facing south, it is shown that the optimally tilted surface receives up to 2% additional annual solar irradiation

MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K.

The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3'-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells

A Novel Adeno-Associated Virus-Based Genetic Vaccine Encoding the Hepatitis C Virus NS3/4 Protein Exhibits Immunogenic Properties in Mice Superior to Those of an NS3-Protein-Based Vaccine.

More than 170 million individuals worldwide are infected with hepatitis C virus (HCV), and up to an estimated 30% of chronically infected individuals will go on to develop progressive liver disease. Despite the recent advances in antiviral treatment of HCV infection, it remains a major public health problem. Thus, development of an effective vaccine is urgently required. In this study, we constructed novel adeno-associated virus (AAV) vectors expressing the full-length NS3 or NS3/4 protein of HCV genotype 1b. The expression of the NS3 or NS3/4 protein in HepG2 cells was confirmed by western blotting. C57BL/6 mice were intramuscularly immunised with a single injection of AAV vectors, and the resultant immune response was investigated. The AAV2/rh32.33.NS3/4 vaccine induced stronger humoral and cellular responses than did the AAV2/rh32.33.NS3 vaccine. Our results demonstrate that AAV-based vaccines exhibit considerable potential for the development of an effective anti-HCV vaccine

Serum estradiol to testosterone ratio as a novel predictor of severe preeclampsia in the first trimester

Abstract Preeclampsia (PE) is the most common medical complication during pregnancy and the second leading cause of maternal death worldwide. However, a better predictive model of PE remains to be explored. A total of 15 severe preeclampsia (sPE) and 75 healthy control patients were included in this study. Patient data was obtained from September 2019 to September 2021. Nuchal translucency (NT) and crown‐rump length (CRL) of the fetus were acquired by ultrasound. Maternal blood samples were collected at 11+0 to 13+6 weeks of gestation. Chemiluminescent immunoassays were used to detect serum testosterone (T) and estradiol (E2) levels. Time‐resolved fluorescence analysis was used to examine the levels of serum pregnancy‐associated plasma protein A (PAPPA) and β‐human chorionic gonadotrophin (β‐HCG) protein. The sPE group exhibited increased T levels, and decreased E2 levels and E2/T ratios from 11 to 14 weeks of gestation, compared with the control group. E2 and the E2/T ratio showed positive linear correlation with CRL in pregnant women. Body‐mass‐index (BMI), T, and E2 were determined to be the main factors that affected the occurrence of sPE at the 12‐week gestation period time point. The receiver operating characteristic (ROC) curve revealed that the AUC of the E2/T ratio was .717. The imbalanced T and E2 levels in the patients had a specific intrinsic relevance with sPE, which suggests them as novel predictors of the sPE

Overexpression of miR-27a in nucleus pulposus cells, and its function in the regulation of target proteins

<p>(A) Comparison of cell proliferation in various NP cell groups (*P<0.05). Data are representative of three experiments; error bars represent SEM. (B) Increased expression of cleaved caspase 3 and decreased expression of PIK3CD in the group overexpressing miR-27a compared to the control group (magnification ×200), respectively. Black arrows indicate positive-stained cells. (C) Contour diagram of FITC-Annexin V/PI FCM of human NP cells. The graphs represent typical results of cellular apoptosis; values represent the means of three experiments. Error bars represent SEM. (D) Results of cellular apoptosis was expressed as a fold change. Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05, ***P<0.001). (E) Increased numbers of nucleus pulposus cells were observed to undergo apoptosis in the group overexpressing miR-27a compared to the control group (magnification ×200). (F) (G) After 36 h, cellular protein lysates were prepared and PIK3CD expression was assessed by Western blot. GAPDH was used as an internal loading standard. Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05, **P<0.01).</p

MiR-27a can inhibit PIK3CD by targeting the 3’-UTRs of PIK3CD.

<p>(A) Complementarity between miR-27a and the putative PIK3CD 3’-UTR target site. PIK3CD 3’-mut indicates the PIK3CD 3’-UTRs with three mutation sites (underlined) in miR-27a binding sites. (B) The relative luciferase activities of three independent experiments are shown. Error bars represent SEM; (**P<0.01).</p