Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus

Anion-induced robust ferroelectricity in sulfurized pseudo-rhombohedral epitaxial BiFeO3 thin films via polarization rotation

Polarization rotation caused by various strains, such as substrate and/or chemical strain, is essential to control the electronic structure and properties of ferroelectric materials. This study proposes anion-induced polarization rotation with chemical strain, which effectively improves ferroelectricity. A method for the sulfurization of BiFeO3 thin films by introducing sulfur anions is presented. The sulfurized films exhibited substantial enhancement in room-temperature ferroelectric polarization through polarization rotation and distortion, with a 170% increase in the remnant polarization from 58 to 100.7 μC cm−2. According to first-principles calculations and the results of X-ray absorption spectroscopy and high-angle annular dark-field scanning transmission electron microscopy, this enhancement arose from the introduction of S atoms driving the re-distribution of the lone-pair electrons of Bi, resulting in the rotation of the polarization state from the [001] direction to the [110] or [111] one. The presented method of anion-driven polarization rotation might enable the improvement of the properties of oxide materials.This work was supported by the National Key Research and Development Program of China (2018YFA0703700, 2017YFE0119700, 2021YFA1400300 and 2018YFA0305700), the National Natural Science Foundation of China (21801013, 51774034, 22271309, 11721404, 11934017, 12261131499, and 51961135107), the Fundamental Research Funds for the Central Universities (FRF-IDRY-19-007 and FRF-TP-19-055A2Z), the National Program for Support of Top-notch Young Professionals, the Young Elite Scientists Sponsorship Program by CAST (2019-2021QNRC), the Beijing Natural Science Foundation (Z200007), and the Chinese Academy of Sciences (XDB33000000). This research used the resources of the Beijing Synchrotron Radiation Facility (1W1A and 4B9B beamlines) of the Chinese Academy of Science.Peer reviewe

Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization

ObjectivesOur aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.MethodsWe extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.ResultsTwo taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.ConclusionsGut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases

Smart Sensor and Sensor Node Design Based on WGSN Data Interface Standard

The standardized configuration methods of sensors and sensor nodes were presented based on the basis of the sensor signal and data interface standardization efforts of China Standardization Working Group on Sensor Networks (WGSN). The self-descriptive digital communication sensors that can be configured by the sensor nodes were designed and developed. And the sensor nodes could automatically identify the docking sensors. The application demo indicates that sensor node can automatically identify the accessing sensors and completes the corresponding configuration, which can also calibrate these sensors

Study on the Impact Resistance of Metal Flexible Net to Rock fall

Based on experiments and finite element analysis, the impact resistance of metal flexible net was studied, which can provide reference for the application of metal flexible net in rock fall protection. The oblique (30 degrees) impact experiment of metal flexible net was carried out, the corresponding finite element (FE) to the experiment was established, and the FE model was verified by simulation results to the experimental tests from three aspects: the deformation characteristics of metal flexible net, the time history curves of impact force on supporting ropes, and the maximum instantaneous impact force on supporting ropes. The FE models of metal flexible nets with inclination angles of 0, 15, 30, 45, 60, and 75 degrees were established, and the impact resistance of metal flexible nets with different inclination angles was analyzed. The research shows that the metal flexible net with proper inclination can bounce the impact rock fall out of the safe area and prevent rock fall falling on the metal flexible net, thus realizing the self-cleaning function. When the inclination angle of the metal flexible net is 15, 30, and 45 degrees, respectively, the bounce effect after impact is better, the remaining height is improved, the protection width is improved obviously, and the impact force is reduced. Herein, the impact force of rock fall decreases most obviously at 45 degrees inclination, and the protective performance is relatively good