Branched-chain amino acid catabolic defect in vascular smooth muscle cells drives thoracic aortic dissection via mTOR hyperactivation.

Metabolic reprogramming of vascular smooth muscle cell (VSMC) plays a critical role in the pathogenesis of thoracic aortic dissection (TAD). Previous researches have mainly focused on dysregulation of fatty acid or glucose metabolism, while the impact of amino acids catabolic disorder in VSMCs during the development of TAD remains elusive. Here, we identified branched-chain amino acid (BCAA) catabolic defect as a metabolic hallmark of TAD. The bioinformatics analysis and data from human aorta revealed impaired BCAA catabolism in TAD individuals. This was accompanied by upregulated branched-chain α-ketoacid dehydrogenase kinase (BCKDK) expression and BCKD E1 subunit alpha (BCKDHA) phosphorylation, enhanced vascular inflammation, and hyperactivation of mTOR signaling. Further in vivo experiments demonstrated that inhibition of BCKDK with BT2 (a BCKDK allosteric inhibitor) treatment dephosphorylated BCKDHA and re-activated BCAA catabolism, attenuated VSMCs phenotypic switching, alleviated aortic remodeling, mitochondrial reactive oxygen species (ROS) damage and vascular inflammation. Additionally, the beneficial actions of BT2 were validated in a TNF-α challenged murine VSMC cell line. Meanwhile, rapamycin conferred similar beneficial effects against VSMC phenotypic switching, cellular ROS damage as well as inflammatory response. However, co-treatment with MHY1485 (a classic mTOR activator) reversed the beneficial effects of BT2 by reactivating mTOR signaling. Taken together, the in vivo and in vitro evidence showed that impairment of BCAA catabolism resulted in aortic accumulation of BCAA and further caused VSMC phenotypic switching, mitochondrial ROS damage and inflammatory response via mTOR hyperactivation. BCKDK and mTOR signaling may serve as the potential drug targets for the prevention and treatment of TAD.

Epidemiology of Hand, Foot, and Mouth Disease and Genetic Evolutionary Characteristics of Coxsackievirus A10 in Taiyuan City, Shanxi Province from 2016 to 2020.

In recent years, the prevalence of hand, foot, and mouth disease (HFMD) caused by enteroviruses other than enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) has gradually increased. The throat swab specimens of 2701 HFMD cases were tested, the VP1 regions of CVA10 RNA were amplified using RT-PCR, and phylogenetic analysis of CVA10 was performed. Children aged 1-5 years accounted for the majority (81.65%) and boys were more than girls. The positivity rates of EV-A71, CVA16, and other EVs were 15.22% (219/1439), 28.77% (414/1439), and 56.01% (806/1439), respectively. CVA10 is one of the important viruses of other EVs. A total of 52 CVA10 strains were used for phylogenetic analysis based on the VP1 region, 31 were from this study, and 21 were downloaded from GenBank. All CVA10 sequences could be assigned to seven genotypes (A, B, C, D, E, F, and G), and genotype C was further divided into C1 and C2 subtypes, only one belonged to subtype C1 and the remaining 30 belonged to C2 in this study. This study emphasized the importance of strengthening the surveillance of HFMD to understand the mechanisms of pathogen variation and evolution, and to provide a scientific basis for HFMD prevention, control, and vaccine development.

Epidemiology of hand, foot, and mouth disease and the genetic characteristics of Coxsackievirus A16 in Taiyuan, Shanxi, China from 2010 to 2021.

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by human enteroviruses (EV). This study aimed to describe the epidemiological features of HFMD and the genetic characteristics of Coxsackievirus A16 (CVA16) in Taiyuan, Shanxi, China, from 2010 to 2021. Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD and the genetic characteristics of CVA16. Except being affected by the COVID-19 epidemic in 2020, HFMD epidemics were sporadic from January to March each year, and began to increase in April, with a major epidemic peak from May to August, which declined in September, followed by a secondary peak from October to December. The prevalence of EV infection was the highest in children aged one to five years (84.42%), whereas its incidence was very low in children under one year of age (5.48%). Enterovirus nucleic acid was detected by real-time reverse transcription polymerase chain reaction in 6641 clinical specimens collected from patients with HFMD from 2010 to 2021, and 4236 EV-positive specimens were detected, including 988 enterovirus A71 (EV-A71), 1488 CVA16, and 1760 other enteroviruses. CVA16 remains prevalent and has co-circulated with other EVs in Taiyuan from 2010 to 2021. A phylogenetic tree constructed based on the VP1 region showed that all CVA16 strains belonged to two different clades of the B1 genotype, B1a and B1b. They showed a nucleotide similarity of 86.5-100%, and an amino acid similarity of 96.9-100%. Overall, these findings add to the global genetic resources of CVA16, demonstrate the epidemiological characteristics of HFMD as well as the genetic features of CVA16 in Taiyuan City during 2010-2021, and provide supporting evidence for the prevention and control of HFMD.

Characteristics of Plantar Pressure Distribution in Diabetes with or without Diabetic Peripheral Neuropathy and Peripheral Arterial Disease.

Background: Excessive plantar pressure leads to increased risk of diabetic foot ulcers. Diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) have been considered to be associated with alterations in gait and plantar pressure in diabetic patients. However, few studies have differentiated the effects with each of them. Objective: To investigate the plantar pressure distribution in diabetic patients, with DPN and PAD as independent or combined factors. Methods: 112 subjects were recruited: 24 diabetic patients with both DPN and PAD (DPN-PAD group), 12 diabetic patients with DPN without PAD (DPN group), 10 diabetic patients with PAD without DPN (PAD group), 23 diabetic patients without DPN or PAD, and 43 nondiabetic healthy controls (HC group). The in-shoe plantar pressure during natural walking was measured. Differences in peak pressure, contact area, proportion of high pressure area (%HP), and anterior/posterior position of centre of pressure (COP) were analysed. Results: Compared with HC group, in DPN-PAD group and DPN group, the peak pressures in all three forefoot regions increased significantly; in PAD group, the peak pressure in lateral forefoot increased significantly. The contact area of midfoot in the DPN-PAD group decreased significantly. PAD group had larger HP% of lateral forefoot, DPN group had larger HP% of inner forefoot, and DPN-PAD group had larger HP% of total plantar area. There was a significant tendency of the anterior displacement of COP in the DPN-PAD group and DPN group. No significant differences were observed between the D group and HC group. Conclusion: DPN or PAD could affect the plantar pressure distribution in diabetic patients independently or synergistically, resulting in increased forefoot pressure and the area at risk of ulcers. DPN has a more pronounced effect on peak pressure than PAD. The synergistic effect of them could significantly reduce the plantar contact area of midfoot.

Suitability evaluation on material specifications and edible methods of Dendrobii Officinalis Caulis based on holistic polysaccharide marker.

BACKGROUND: Dendrobii Officinalis Caulis (DC) is a well-known tonic herbal medicine worldwide and has favorable immunomodulatory activity. Various material specifications of DC are available in herbal markets, and DC is ingested by different edible methods. However, whether these specifications and edible methods are suitable or not remains unknown. METHODS: In this study, we evaluated the suitability of four material specifications (fresh stem, dried stem, fengdou and powder) and three edible methods (making tea, soup and medicinal liquor) based on holistic polysaccharide marker (HPM), the major polysaccharide components in DC. First, the HPMs were extracted from the four specifications of DC by the three edible methods in different conditions. Second, qualitative and quantitative characterization of the extracted HPMs was performed using high performance gel permeation chromatography (HPGPC). Third, immunomodulatory activities of the extracted HPMs were evaluated in vivo. RESULTS: The results showed that the HPMs were found to be quantitatively different from various specification of DC and edible methods. In vivo analysis indicated that the HPMs exerted positive effects on innate immune responses by increment in proliferation of splenocytes, secretion of IL-2 and cytotoxicity activity of NK cells. Moreover, the dosage amount of HPM should be defined as a certain range, but not the larger the better, for exerting strong immunological activities. CONCLUSION: According to the both chemical and biological results, fengdou by boiling with water for 4 h is the most recommended specification and edible method for DC.

[Finite element analysis on biomechanical properties of medial collateral ligament of elbow joint under different flexion angles].

Three-dimensional finite element model of elbow was established to study the effect of medial collateral ligament (MCL) in maintaining the stability of elbow joint. In the present study a three-dimensional geometric model of elbow joint was established by reverse engineering method based on the computed tomography (CT) image of healthy human elbow. In the finite element pre-processing software, the ligament and articular cartilage were constructed according to the anatomical structure, and the materials and contacts properties were given to the model. In the neutral forearm rotation position and 0° flexion angle, by comparing the simulation data of the elbow joint with the experimental data, the validity of the model is verified. The stress value and stress distribution of medial collateral ligaments were calculated at the flexion angles of elbow position in 15°, 30°, 45°, 60°, 75°, 90°, 105°, 120°, 135°, respectively. The result shows that when the elbow joint loaded at different flexion angles, the anterior bundle has the largest stress, followed by the posterior bundle, transverse bundle has the least, and the stress value of transverse bundle is trending to 0. Therefore, the anterior bundle plays leading role in maintaining the stability of the elbow, the posterior bundle plays supplementary role, and the transverse bundle does little. Furthermore, the present study will provide theoretical basis for clinical recognizing and therapy of elbow instability caused by medial collateral ligament injury.

Serum irisin associates with breast cancer to spinal metastasis.

The aim of this study was to determine whether the serum level of irisin can be a candidate to predict the spinal metastasis in patients with breast cancer.In a cross-sectional study, 148 patients were recruited. Of those, 53 (35.8%) had spinal metastasis. The baseline characteristics were compared by status of spinal metastasis. Multiple logistic regression analysis was used to determine whether the serum irisin can be a candidate for predicting breast cancer to spinal metastasis. The correlation coefficient analysis was used to confirm the correlation between the serum irisin and lipid metabolic parameters and body mass index (BMI), respectively.The serum irisin was higher in patients without spinal metastasis (7.60 ±â€Š3.80). Multivariable analysis showed that the serum irisin was protective to the presence of spinal metastasis in patients with breast cancer after adjustments of age and BMI (odds ratio, 0.873; 95% confidence interval, 0.764-0.999). Furthermore, there was a positive correlation between the serum irisin and BMI (r = 0.263). The patients with metabolisc syndrome (MetS) had a higher level in serum irisin. In addition, the higher numbers of MetS components were associated with higher serum irisin.Higher serum irisin can be a protective factor of spinal metastasis in patients with breast cancer. The BMI is positively associated with the serum level of irisin. Furthermore, patients with MetS tended to have a higher level of serum irisin.

Oolong tea: A critical review of processing methods, chemical composition, health effects, and risk.

Oolong tea (OT) is a traditional Chinese tea (Camellia sinensis) and is especially popular in south China. This review is to comprehensively summarize the miscellaneous research that has been done towards to the processing, phytochemistry, health benefit, and risk of OT. These literatures were carried out not only from different electronic databases but also from text books written in English, Japanese, and Chinese, including those traditional records tracing back to the Tang Dynasty (A.D. 618-907). The full process OT producing is depicted below in this review. The phytochemistry of OT has been comprehensively investigated. More than 100 chemical compositions have been isolated and identified. In health benefit, OT performs outstandingly in reducing obesity and controlling diabetes explained by modern pharmacological studies. (-)-Epigallocatechin-3-gallate (6) in OT prevention of cancerous cells developing. OT can also improve and reduce on heart and vascular disease, protect teeth and bone, function as anti-oxidative and antibacterial agents. This review also mentioned the risk, summarized briefly on various forms of toxicity and harmful associated with OT. In short, this review can provided a natural product library of OT, gave inspirations for further new garden systems, designed idea on quality, bioactivity-oriented screening. In addition, it is suggested more scientists and education is necessary to guarantee the stability and safety of drinking OT.