Clinical effect of astragaloside IV on breast carcinoma cells based on MDR1: A randomised trial

Purpose: To study the clinical effect of astragaloside IV on breast carcinoma cells (BCCs), and its potential mechanisms with respect to multiple drug resistance-1 (MDR1)Methods: The cytotoxicity of astragaloside IV to BCCs was determined using CCK-8 test, and values of its half inhibitory concentration (IC50) were determined. Transwell assay and flow cytometry were performed to determine the effect of astragaloside (13 μg/mL) on cell invasion and apoptosis. The contents of MDR1 mRNA in BC tissues and cells were determined using real-time quantitative polymerase chain reaction (qRT-PCR), while the protein expression levels of MDR1 in BC cells were determined using western blot assay.Results: The IC50 of astragaloside IV for MCF-7 and MDA-MB-231 BCCs were 12.57 μg/mL and 13.91 μg/mL, respectively. Transwell experiment showed significantly inhibited invasive capacity and enhanced apoptotic potential of the BCCs after astragaloside IV intervention. However, invasive capacities of the BCCs were markedly enhanced, while their apoptotic capacities were inhibited after transfection with si-MDR1, when compared with controls (p < 0.05). Results of qRT-PCR revealed that the mRNA content of MDR1 in BC tissues and cells (0.42±0.11) was significantly lower than that in normal tissues (0.95±0.18; p < 0.05). Results from western blot assay revealed that the relative expression levels of MDR1 protein were decreased, with values of 0.21±0.05, 0.32±0.07 and 0.74±0.15 for MCF-10A, MCF-7, MAD-MB-231 and MCF-10A, respectively (p < 0.05).Conclusion: Astragaloside IV regulates the metastasis and apoptosis of BCCs through regulation of MDR1. It also inhibits cell invasion but enhances the apoptosis of BC cells transfected with si-MDR1. These results highlight the prospects of the compound for the treatment of BC

Highly Efficient CRISPR-Mediated Base Editing in Sinorhizobium meliloti

Rhizobia are widespread gram-negative soil bacteria and indispensable symbiotic partners of leguminous plants that facilitate the most highly efficient biological nitrogen fixation in nature. Although genetic studies in Sinorhizobium meliloti have advanced our understanding of symbiotic nitrogen fixation (SNF), the current methods used for genetic manipulations in Sinorhizobium meliloti are time-consuming and labor-intensive. In this study, we report the development of a few precise gene modification tools that utilize the CRISPR/Cas9 system and various deaminases. By fusing the Cas9 nickase to an adenine deaminase, we developed an adenine base editor (ABE) system that facilitated adenine-to-guanine transitions at one-nucleotide resolution without forming double-strand breaks (DSB). We also engineered a cytidine base editor (CBE) and a guanine base editor (GBE) that catalyze cytidine-to-thymine substitutions and cytidine-to-guanine transversions, respectively, by replacing adenine deaminase with cytidine deaminase and other auxiliary enzymes. All of these base editors are amenable to the assembly of multiple synthetic guide RNA (sgRNA) cassettes using Golden Gate Assembly to simultaneously achieve multigene mutations or disruptions. These CRISPR-mediated base editing tools will accelerate the functional genomics study and genome manipulation of rhizobia

Reduction of satellite flywheel microvibration using rubber shock absorbers

Microvibration of flywheels strongly affects the imaging quality of space cameras. A passive vibration method is used in this study to reduce the effect of microvibration. A rubber shock absorber was designed and installed on a satellite. The angular displacement of the second mirror was measured via a fiber optic gyroscopic method. The measured data were imported into MATLAB and analyzed by different methods. The data was plotted as a root-mean-square graph of angular displacement at different speeds along the x-axis, a waterfall plot of the attenuation of force in the x direction, the vibration spectrum between the frequency and displacement amplitude, and the time domain response of the inverse Fourier transform of the spectrum. The results show that the microvibration of the flywheel causes significant vibration of the imaging system, and that adding a rubber shock absorber can reduce the vibration. The proposed method is a new attempt to analyze microvibration, and can be applied to the engineering design of flywheels

Reduction of satellite flywheel microvibration using rubber shock absorbers

Microvibration of flywheels strongly affects the imaging quality of space cameras. A passive vibration method is used in this study to reduce the effect of microvibration. A rubber shock absorber was designed and installed on a satellite. The angular displacement of the second mirror was measured via a fiber optic gyroscopic method. The measured data were imported into MATLAB and analyzed by different methods. The data was plotted as a root-mean-square graph of angular displacement at different speeds along the x-axis, a waterfall plot of the attenuation of force in the x direction, the vibration spectrum between the frequency and displacement amplitude, and the time domain response of the inverse Fourier transform of the spectrum. The results show that the microvibration of the flywheel causes significant vibration of the imaging system, and that adding a rubber shock absorber can reduce the vibration. The proposed method is a new attempt to analyze microvibration, and can be applied to the engineering design of flywheels

Disability transitions and health expectancies among elderly people aged 65 years and over in China: A nationwide longitudinal study

Disability has become a critical issue among elderly populations, yet limited large-scale research related to this issue has been conducted in China, an aging society. This study explored sex and urban-rural differences in disability transitions and life expectancies among older adults in China. Data were collected from the Chinese Longitudinal Health Longevity Survey (CLHLS), which enrolled people aged 65 and older and was conducted in randomly selected counties and cities across 22 provinces in China. Disability was diagnosed based on basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). Several individual characteristics were assessed, including sociodemographic factors (age, sex and region, etc.) and health behaviors (currently smoking, currently drinking, etc.). Multistate models were applied to analyze the transition rates among 4 states: no disability, mild disability, severe disability and death. The transition rates from disabled states to the no-disability state were found to decrease markedly with age. The rates of recovery from mild disability in rural areas were higher than those in urban areas. Rural elderly individuals lived shorter lives than their urban counterparts, but they tended to live with better functional status, spending a larger fraction of their remaining life with less severe disability. Based on these findings, devoting more attention and resources to rural areas may help less severely disabled people recuperate and prevent severe disability. The study provides insights into health plan strategies to help guide the allocation of limited resources

Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis

Homocysteine (Hcy) is an intermediate amino acid formed during the conversion from methionine to cysteine. When the fasting plasma Hcy level is higher than 15 μmol/L, it is considered as hyperhomocysteinemia (HHcy). The vascular endothelium is an important barrier to vascular homeostasis, and its impairment is the initiation of atherosclerosis (AS). HHcy is an important risk factor for AS, which can promote the development of AS and the occurrence of cardiovascular events, and Hcy damage to the endothelium is considered to play a very important role. However, the mechanism by which Hcy damages the endothelium is still not fully understood. This review summarizes the mechanism of Hcy-induced endothelial injury and the treatment methods to alleviate the Hcy induced endothelial dysfunction, in order to provide new thoughts for the diagnosis and treatment of Hcy-induced endothelial injury and subsequent AS-related diseases

Critical Roles of STAT3 in β-Adrenergic Functions in the Heart

BACKGROUND: β-Adrenergic receptors (βARs) play paradoxical roles in the heart. On one hand, βARs augment cardiac performance to fulfill the physiological demands, but on the other hand, prolonged activations of βARs exert deleterious effects that result in heart failure. The signal transducer and activator of transcription 3 (STAT3) plays a dynamic role in integrating multiple cytokine signaling pathways in a number of tissues. Altered activation of STAT3 has been observed in failing hearts in both human patients and animal models. Our objective is to determine the potential regulatory roles of STAT3 in cardiac βAR-mediated signaling and function. METHODS AND RESULTS: We observed that STAT3 can be directly activated in cardiomyocytes by β-adrenergic agonists. To follow up this finding, we analyzed βAR function in cardiomyocyte-restricted STAT3 knockouts and discovered that the conditional loss of STAT3 in cardiomyocytes markedly reduced the cardiac contractile response to acute βAR stimulation, and caused disengagement of calcium coupling and muscle contraction. Under chronic β-adrenergic stimulation, Stat3cKO hearts exhibited pronounced cardiomyocyte hypertrophy, cell death, and subsequent cardiac fibrosis. Biochemical and genetic data supported that Gαs and Src kinases are required for βAR-mediated activation of STAT3. Finally, we demonstrated that STAT3 transcriptionally regulates several key components of βAR pathway, including β1AR, protein kinase A, and T-type Ca(2+) channels. CONCLUSIONS: Our data demonstrate for the first time that STAT3 has a fundamental role in βAR signaling and functions in the heart. STAT3 serves as a critical transcriptional regulator for βAR-mediated cardiac stress adaption, pathological remodeling, and heart failure

A low‐profile wide‐angle scanning ultrawideband tightly coupled dipole array without any wide‐angle impedance matching layer

Abstract The present is a low‐profile, wide‐angle scanning, ultrawideband, tightly coupled dipole array that lacks a wide‐angle impedance matching layer and lossy materials. Impedance matching will deteriorate at the lower end of the operating bandwidth due to the influence of the ground plane. A well‐designed perforated balun is used to achieve better impedance matching. Moreover, parasitic metallic strips are attached to the dipole's side to add additional reactive components. According to the results of simulations, the impedance bandwidth of the array, which ranges from 0.67 to 2.83 GHz, and its wide‐angle scanning capability, which scans 75° in the E‐plane and 45° in the H‐plane, both achieve good performance when the voltage standing wave ratio is less than 3. The profile of the array is only 0.0581λlow above the ground plane, where λlow is the wavelength at the lowest operating frequency. The proposed array's simulated results are validated by fabricating and measuring an 8 × 8 prototype array