Identifying sm22 as a key player in arterial diseases

Background : Expression of vascular smooth muscle cell (VSMC) cytoskeleton markers including SM22 is down-regulated in arterial diseases including atherosclerosis where inflammation and osteochondrogenesis are present. However, the role of this downregulation in arterial pathogenesis is unknown. Hypothesis : Downregulation of SM22 may actively contribute to arterial pathogenesis. Methods : Five Sm22 knockout (Sm22-/-) mice and their wild type littermates were subjected to carotid artery denudation, an artery injury model. Analyses were conducted on carotid arteries 2 weeks after injury. Primary VSMCs were isolated from mouse aortas and investigated individually at passage 2 to 4. Sm22 knockdown was performed in triplicate using siRNA in a VSMC line, PAC1, followed by downstream experiments 3 days after transfection. Results : Sm22-/- mice developed both enhanced arterial inflammatory response and prominent medial chondrogenesis along with remarkable NF-ΚB activation compared to their wild-type littermates. The inflammation was evidenced by excessive artery swelling, macrophage infiltration and high induction of pro-inflammatory molecules including Vcam1, Icam1, Cx3cl1, Ptgs2 and Ccl2. The medial chondrogenesis was characterized by augmented expression of type II collagen, aggrecan, osteopontin, Bmp2 and the key osteochondrogenic transcription factors Sox9. In accordance with the in vivo findings, expression of the aforementioned pro-inflammatory genes and Sox9 was up-regulated in Sm22-/- primary VSMCs and after Sm22 knockdown in PAC1 cells. Interestingly, Sm22 knockdown also led to NF-ΚB activation, and inhibition of NF-ΚB pathway reversed the up-regulation of both pro-inflammatory genes and Sox9. As an initiator of NF-ΚB activation, reactive oxygen species (ROS) production was boosted in Sm22-/- primary VSMCs and after Sm22 knockdown. ROS scavengers effectively blocked NF-ΚB activation and induction of both pro-inflammatory genes and Sox9 after Sm22 knockdown. Further, the altered cell morphology and increased actin dynamics after Sm22 knockdown might contribute to the elevated ROS. Conclusions : These findings suggest that loss of Sm22 in VSMCs coupled injury induced arterial inflammation with chondrogenesis in part via ROS induced NF-ΚB activation and that Sm22 plays both anti-inflammatory and anti-osteochondrogenic roles in arterial diseases partly by maintaining actin cytoskeleton integrity

Structure Analysis for Tunnel Longitudinal Deformation Based on Segment Dislocation Mode

AbstractAccording to tunnel structure around joints, tunnel longitudinal deformation is analyzed and a three-dimensional finite element model is built based on segment dislocation mode. Tunnel structure stress analysis is conducted from two aspects of segment in the shear and bolt in the tension. The analysis results show: (1) Segment shear model. When segment dislocation reaches 0.03mm, the principal stressσ1 exceeds 3.0Mpa which is over concrete's tensile strength. Therefore, when convex tenon and concave tenon generate shear, there must be horizontal slipping and bolt is tensioned. (2) Bolt tension model. When joint opening value reaches 2mm, bolt stress exceeds 640Mpa, which is bolt's yield strength. When joint opening value reaches 6mm, which is the waterproof control standard for tunnel, bolt stress reaches 688.7Mpa, which is less than bolt's failure strength. The subway tunnel's structure safety should be controlled from the perspective of waterproof

General ranked set sampling for efficient treatment comparisons

In treatment comparison experiments, the treatment responses are often correlated with some concomitant variables which can be measured before or at the beginning of the experiments. In this article, we propose schemes for the assignment of experimental units that may greatly improve the efficiency of the comparison in such situations. The proposed schemes are based on general ranked set sampling. The relative efficiency and cost-effectiveness of the proposed schemes are studied and compared. It is found that some proposed schemes are always more efficient than the traditional simple random assignment scheme when the total cost is the same. Numerical studies show promising results using the proposed schemes

AI Assistant in Online Pharmacy

Artificial intelligence (AI) has been increasingly popular in diagnosing diseases and recommending drugs in digital healthcare platforms. Leveraging the introduction of an AI-powered medical assistant to one drug category in an online pharmacy platform, we investigate how the adoption of AI affects users’ purchase behaviors using a difference-in-differences design. We find that the adoption of the AI assistant significantly increases users’ purchases in the platform, even for drugs not recommended by the AI assistant. Furthermore, we find that the positive effect of the AI assistant adoption is stronger for early technology adopters, inexperienced users, and users with higher privacy concerns, likely because these users tend to perceive higher value from AI. Finally, our mediation analysis shows that the AI feature increases users’ purchases by increasing their engagement levels in the platform. Our results have important implications for designing and evaluating AI features in online platforms

Knowledge Collaboration Evolution Mechanisms of IT Service Outsourcing Enterprises: An Analysis Based on a Complex Network

The purpose of this study is to explore the self-organization evolution mechanisms of IT service outsourcing enterprise knowledge systems. First, this paper conducts a microanalysis of knowledge activities and discusses the macro characteristics of different evolution phases of enterprise knowledge collaboration networks. Second, it proposes the dominant factors of knowledge collaboration phases. Finally, it builds a network model of enterprise knowledge systems, calculates network structure parameters to reflect the phase changes in knowledge collaboration, and analyses the evolution path of knowledge systems driven by different dominant factors. This paper uses a knowledge network model based on self-organization theory to study structural problems of enterprise knowledge system evolution, and this model provides practical and theoretical value for solving the problem of knowledge collaboration among IT service outsourcing enterprises

Effects of the manufacturing process on the reliability of the multilayer structure in MetalMUMPs actuators: Residual stresses and variation of design parameters

© 2017 by the authors. Potential problems induced by the multilayered manufacturing process pose a serious threat to the long-term reliability of MEMSCAP® actuators under in-service thermal cycling. Damage would initiate and propagate in different material layers because of a large mismatch of their thermal expansions. In this research, residual stresses and variations of design parameters induced by metal multi-user micro electromechanical system processes (MetalMUMPs) were examined to evaluate their effects on the thermal fatigue lifetime of the multilayer structure and, thus, to improve MEMSCAP® design. Since testing in such micro internal structure is difficult to conduct and traditional testing schemes are destructive, a numerical subdomain method based on a finite element technique was employed. Thermomechanical deformation from metal to insulator layers under in-service temperature cycling (obtained from the multiphysics model of the entire actuator, which was validated by experimental and specified analytical solutions) was accurately estimated to define failures with a significant efficiency and feasibility. Simulation results showed that critical failure modes included interface delamination, plastic deformation, micro cracking, and thermal fatigue, similarly to what was concluded in the MEMSCAP® technical report

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQ™ quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway Analysis™ (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death

Transmission Roles of Symptomatic and Asymptomatic COVID-19 Cases: A Modelling Study

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9–80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0–34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks