Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p><it>CALM1 </it>gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca²⁺-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the <it>CALM1 </it>core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.</p> <p>Methods</p> <p>A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.</p> <p>Results</p> <p>No significant difference was detected in genotype or allele distribution between knee OA and control groups (all <it>P </it>> 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.</p> <p>Conclusion</p> <p>The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.</p

The Ginger-shaped Asteroid 4179 Toutatis: New Observations from a Successful Flyby of Chang'e-2

On 13 December 2012, Chang'e-2 conducted a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 $\pm$ 120 meters from the asteroid's surface. The highest-resolution image, with a resolution of better than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at the big end, a sharply perpendicular silhouette near the neck region, and direct evidence of boulders and regolith, which suggests that Toutatis may bear a rubble-pile structure. Toutatis' maximum physical length and width are (4.75 $\times$ 1.95 km) $\pm$10$\%$, respectively, and the direction of the +$z$ axis is estimated to be (250$\pm$5$^\circ$, 63$\pm$5$^\circ$) with respect to the J2000 ecliptic coordinate system. The bifurcated configuration is indicative of a contact binary origin for Toutatis, which is composed of two lobes (head and body). Chang'e-2 observations have significantly improved our understanding of the characteristics, formation, and evolution of asteroids in general.Comment: 21 pages, 3 figures, 1 tabl

Safety, tolerance, and pharmacokinetics of salvianolic acid B in healthy Chinese volunteers: A randomized, double-blind, placebo-controlled phase 1 clinical trial

Background: Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza Bunge. In China, many traditional Chinese medicines have been modified into injections for higher bioavailability and better efficacy. Salvianolic acid injection has been widely used in the clinic.Objective: This phase 1, randomized, double-blind, placebo-controlled, single-center study aimed to evaluate the safety, tolerance, and pharmacokinetics of Sal B injection in healthy Chinese volunteers.Methods: For the single-ascending-dose study, forty-seven healthy volunteers were randomly divided into 25, 75, 150, 200, 250, and 300 mg groups. For the multiple-ascending-dose study, sixteen healthy volunteers were randomly divided into 150 and 300 mg groups. In each group, volunteers were treated with Sal B or placebo randomly. Their safety was evaluated by a skin test, physical examination, vital sign, laboratory examination, 12-lead electrocardiogram, Holter, and clinical symptoms and signs. Blood samples were collected in 75, 150, and 300 mg single-ascending-dose study groups and 150 mg multiple-ascending-dose study groups to determine the concentration of salvianolic acid B.Results: In single-ascending-dose study groups, there were 41 adverse events in 24 cases (51.1%, 24/47). In multiple-ascending-dose study groups, there were 13 adverse events in eight cases (50.0%, 8/16). Sixty-six volunteers received the skin test, and three of them were excluded because of the positive result. Adverse events related to the treatment included increased alanine aminotransferase (4.0%), increased bilirubin (2.0%), increased creatinine kinase-MB (2.0%), increased brain natriuretic peptide (8.0%), increased urine N-acetyl-β-D-glucosidase (4.0%), dizziness (2.0%), and chest discomfort (2.0%). No serious adverse events occurred. No volunteers withdrew from the trial. Peak plasma concentration and the area under the plasma concentration–time curve of salvianolic acid B progressively increased in a dose-dependent manner in 75, 150, and 300 mg single-ascending-dose study groups. There was no accumulation after 5 consecutive days of administration of 150 mg salvianolic acid B.Conclusion: Salvianolic acid B injections administered up to 300 mg in a single dose and 250 mg for 5 consecutive days showed excellent safety and tolerability in healthy Chinese volunteers.Clinical Trial Registration:www.chinadrugtrials.org.cn, identifier CTR2019223

CHES: a space-borne astrometric mission for the detection of habitable planets of the nearby solar-type stars

The Closeby Habitable Exoplanet Survey (CHES) mission is proposed to discover habitable-zone Earth-like planets of the nearby solar-type stars ($\sim 10~\mathrm{pc}$ away from our solar system) via micro-arcsecond relative astrometry. The major scientific objectives of CHES are: to search for Earth Twins or terrestrial planets in habitable zones orbiting 100 FGK nearby stars; further to conduct a comprehensive survey and extensively characterize the nearby planetary systems. The primary payload is a high-quality, low-distortion, high-stability telescope. The optical subsystem is a coaxial three-mirror anastigmat (TMA) with a $1.2 \mathrm{~m}$-aperture, $0.44^{\circ} \times 0.44^{\circ}$ field of view and $500 \mathrm{~nm}-900 \mathrm{~nm}$ working waveband. The camera focal plane is composed of 81 MOSAIC scientific CMOS detectors each with $4 \mathrm{~K} \times 4 \mathrm{~K}$ pixels. The heterodyne laser interferometric calibration technology is employed to ensure micro-arcsecond level (1 $\mu$as) relative astrometry precision to meet the requirements for detection of Earth-like planets. CHES satellite operates at the Sun-Earth L2 point and observes the entire target stars for 5 years. CHES will offer the first direct measurements of true masses and inclinations of Earth Twins and super-Earths orbiting our neighbor stars based on micro-arcsecond astrometry from space. This will definitely enhance our understanding of the formation of diverse nearby planetary systems and the emergence of other worlds for solar-type stars, and finally to reflect the evolution of our own solar system.Comment: 39 pages, 37 figures, Invited Review, accepted to Research in Astronomy and Astrophysic

Association between mobile phone addiction, sleep disorder and the gut microbiota: a short-term prospective observational study

Bidirectional communication between the gut microbiota and the brain has sparked interest in exploring the link between mobile phone addiction (MPA) and sleep disorders (SD) in microbiome research. However, investigating the role of gut microbiota in this relationship using animal models presents challenges due to the unique nature of MPA, and human research in this area is scarce. We recruited 99 healthy college students to evaluate the gut microbiome using 16S rRNA gene amplicon sequencing and assess MPA and SD at baseline and after a two-month follow-up. Multiple covariate-adjusted statistical models, including linear regression, permutational multivariate analysis of variance and so on, were employed to determine microbiome associations with MPA at baseline and changes in SD at follow-up. Our findings revealed negative associations between MPA and three alpha diversity metrics, along with alterations in bacterial composition. MPA showed negative associations with the relative abundance of Bacteroidetes, while displaying positive associations with Actinobacteria and Bifidobacteriales. Conversely, Actinobacteria exhibited a negative association with increased SD. This study has established a significant link between MPA and a decrease in the alpha diversity of the gut microbiota. Actinobacteria was associated with MPA and SD, respectively. Additional investigation is needed to fully comprehend the relationship between comorbid behavioral disorders and the gut microbiota

Research on support mode of Medium Altitude Long Endurance UAS based on the mode of military trade

The Unmanned Aerial System (UAS) is more and more widely used in modern warfare, and its problem of support mode is becoming more and more prominent. The support mode of UAS refers to the standard mode to ensure the operation and maintenance of UAS which mainly composed of maintenance level, organization structure and contractor logistical support system. In most cases the support mode of UAS draws lesson from manned vehicles’. For the research and application of support model of UAS is relatively lagging, for example, the division of maintenance level is not clear; the allocation of support resources is redundant; military force lacks maintenance support capability; logistical support professional setting is not reasonable; the contractor logistics support system is not normative. So, there is no a set of effective, reasonable and normative support mode to support the operation and maintenance of UAS, resulting in the operational readiness of UAS is not high and maintenance process wastes a lot of manpower and material and money, which greatly restricts the operation and development of UAS. Combined with the UAS support requirements and features under the military trade, this paper analyses the status of the redundant and inefficient support mode. Aiming at these problem, a new support model of UAS will be researched from three aspects including the allocation of maintenance level, the adjustment of military maintenance organization structure, and the establishment of contractor logistical support system. By applying the new support mode to user, the operation and support of UAS will be more effective and reasonable which will greatly promote the development of UAS