The causal relationship of human blood metabolites with the components of Sarcopenia: a two-sample Mendelian randomization analysis.

BACKGROUND: Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia. METHODS: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed. RESULTS: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10- 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses. CONCLUSION: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

Volcanic history of the Imbrium basin: A close-up view from the lunar rover Yutu.

We report the surface exploration by the lunar rover Yutu that landed on the young lava flow in the northeastern part of the Mare Imbrium, which is the largest basin on the nearside of the Moon and is filled with several basalt units estimated to date from 3.5 to 2.0 Ga. The onboard lunar penetrating radar conducted a 114-m-long profile, which measured a thickness of ∼5 m of the lunar regolith layer and detected three underlying basalt units at depths of 195, 215, and 345 m. The radar measurements suggest underestimation of the global lunar regolith thickness by other methods and reveal a vast volume of the last volcano eruption. The in situ spectral reflectance and elemental analysis of the lunar soil at the landing site suggest that the young basalt could be derived from an ilmenite-rich mantle reservoir and then assimilated by 10-20% of the last residual melt of the lunar magma ocean.

[Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

[Temperature effect correction for Chang'E-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover of China's Lunar Exploration Project. The present paper introduces briefly the components of APXS, how it works and its working environment on the lunar surface. The environmental temperature effect has been studied with simulations and experiments, and the results show that the temperature of the APXS sensor will be varying during the measuring on the lunar surface. And another experiment reveals that the energy resolution becomes worse if the sensor's temperature is varying. In this paper, a correction method based on Pearson's chi-squared test is presented. The method can improve the energy resolution when the sensor's temperature is varying. We have tested the method with the spectra acquired by APXS in the temperature varying period of Temperature Cycling Test, and the results show that the method is efficient and reliable.

Mitochondrial Dysfunction in Atherosclerosis.

Mitochondria are highly dynamic organelles beyond powerhouses of a cell. These components also play important roles in cell homeostasis by regulating cell function and phenotypic modulation. Atherosclerosis is the leading cause of morbidity and mortality in developed and developing countries. Mitochondrial dysfunction has been increasingly associated with the initiation and progression of atherosclerosis by elevating the production of reactive oxygen species and mitochondrial oxidative stress damage, mitochondrial dynamics dysfunction, and energy supply. In this review, we describe the progression of the link between mitochondrial dysfunction and atherosclerosis and its potential regulation mechanisms.

[Application of direct demodulation technique in analysis of ground verification test of x-ray spectrometer for Chang'e mission].

An X-ray fluorescence imaging spectrometer based on silicon PIN photodiodes was designed and constructed for the Chang'E mission, the first lunar spacecraft, and will be in operation at a 200 km circular lunar orbit with one year lifetime. The X-ray fluorescence spectrometer consists of two silicon PIN photodiodes modules, each holds two low energy detector units to analyze the distribution of useful elements and to estimate the abundance on the moon, which is one of the objectives of the X-ray fluorescence spectrometer experiment. The low energy detector unit is 25 mm2, 500 microm thick, with the energy band of 1-10 keV, and energy resolution of: approximately 5% at 5.9 keV. The ground verification tests of the X-ray spectrometer for Chang' E mission were introduced in the present paper. Taking the energy response matrix of the spectrometer as the foundation and using the direct demodulation technique and fundamental parameter method, the authors performed some quantitative and qualitative analysis of these scientific data which came from the ground verification tests, especially for Mg, Al and Si elements.

Endothelial-to-Mesenchymal Transition: A Potential Mechanism for Atherosclerosis Plaque Progression and Destabilization.

Endothelial-to-mesenchymal transition (EndMT) is a cellular reprogramming mechanism by which endothelial cells acquire a mesenchymal phenotype. EndMT is associated with fibroproliferative diseases, such as cancer progression and metastasis and cardiac and kidney fibrosis, and this condition has been extensively investigated over the past decade. Recently, studies showed that EndMT contributes to the initiation and progression of atherosclerotic lesion and plaque destabilization. Unstable atherosclerotic plaque rupture and subsequent thrombosis are the main pathological causes of acute cardiovascular events. EndMT is plastic and reversible. Therefore, our enhanced understanding on the mechanisms controlling EndMT and its roles in the atherosclerosis plaque progression and instability may provide a basis for the development of novel therapeutic strategies to stabilize and reverse atherosclerotic plaques.

Correlated compositional and mineralogical investigations at the Chang'e-3 landing site.

The chemical compositions of relatively young mare lava flows have implications for the late volcanism on the Moon. Here we report the composition of soil along the rim of a 450-m diameter fresh crater at the Chang'e-3 (CE-3) landing site, investigated by the Yutu rover with in situ APXS (Active Particle-induced X-ray Spectrometer) and VNIS (Visible and Near-infrared Imaging Spectrometer) measurements. Results indicate that this region's composition differs from other mare sample-return sites and is a new type of mare basalt not previously sampled, but consistent with remote sensing. The CE-3 regolith derived from olivine-normative basaltic rocks with high FeO/(FeO+MgO). Deconvolution of the VNIS data indicates abundant high-Ca ferropyroxene (augite and pigeonite) plus Fe-rich olivine. We infer from the regolith composition that the basaltic source rocks formed during late-stage magma-ocean differentiation when dense ferropyroxene-ilmenite cumulates sank and mixed with deeper, relatively ferroan olivine and orthopyroxene in a hybridized mantle source.