DHCR24 Insufficiency Promotes Vascular Endothelial Cell Senescence and Endothelial Dysfunction via Inhibition of Caveolin-1/ERK Signaling.

Endothelial cells (ECs) senescence is critical for vascular dysfunction, which leads to age-related disease. DHCR24, a 3ß-hydroxysterol δ 24 reductase with multiple functions other than enzymatic activity, has been involved in age-related disease. However, little is known about the relationship between DHCR24 and vascular ECs senescence. We revealed that DHCR24 expression is chronologically decreased in senescent human umbilical vein endothelial cells (HUVECs) and the aortas of aged mice. ECs senescence in endothelium-specific DHCR24 knockout mice was characterized by increased P16 and senescence-associated secretory phenotype, decreased SIRT1 and cell proliferation, impaired endothelium-dependent relaxation, and elevated blood pressure. In vitro, DHCR24 knockdown in young HUVECs resulted in a similar senescence phenotype. DHCR24 deficiency impaired endothelial migration and tube formation and reduced nitric oxide (NO) levels. DHCR24 suppression also inhibited the caveolin-1/ERK signaling, probably responsible for increased reactive oxygen species production and decreased eNOS/NO. Conversely, DHCR24 overexpression enhanced this signaling pathway, blunted the senescence phenotype, and improved cellular function in senescent cells, effectively blocked by the ERK inhibitor U0126. Moreover, desmosterol accumulation induced by DHCR24 deficiency promoted HUVECs senescence and inhibited caveolin-1/ERK signaling. Our findings demonstrate that DHCR24 is essential in ECs senescence.

Fibulin 1, targeted by microRNA-24-3p, promotes cell proliferation and migration in vascular smooth muscle cells, contributing to the development of atherosclerosis in APOE-/- mice.

Extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) are the main components of atherosclerosis (AS) plaque. VSMCs participate in plaque formation through phenotypic transformation. The complex interplay between ECM and VSMCs plays vital roles in the progression of AS throughout the disease. An in-depth investigation into the functions of ECM-related molecules in VSMC development might contribute to deciphering the complexity of AS pathogenesis. In this study, the roles and molecular mechanisms of the ECM-related molecule Fibulin-1 (FBLN1) in the development of AS and VSMCs were explored using RNA sequencing, bioinformatics analysis, and cell experiments. Furthermore, the expression of FBLN1, as determined by western blot analysis, immunohistochemistry, and real-time quantitative PCR, was significantly increased in AS vascular samples compared to normal vascular samples. Silencing the FBLN1 through AAV viral injection in mice revealed an improvement in AS. Functional analyses revealed that FBLN1 promoted VSMC proliferation, migration, and wound healing. Combined with RNA sequencing and TargetScan7.2 prediction data, 22 microRNAs (miRNAs) were found to have the potential for direct interaction with the FBLN1 3'UTR in VSMCs. Among these 22 miRNAs, it was demonstrated that microRNA-24-3p (miR-24-3p) could negatively regulate FBLN1 expression by directly binding to the FBLN1 3'UTR. Moreover, miR-24-3p inhibited cell proliferation, migration, and wound healing, and suppressed the expression of Ki67, matrix metalloproteinase-2 and -9 (MMP2/9) by targeting FBLN1 in VSMCs. Meanwhile, inhibition of FBLN1 expression could restrain VSMC phenotypic transformation. In conclusion, miR-24-3p inhibited VSMC proliferation and migration by targeting FBLN1. Additionally, multiple miRNAs with the potential to interact with the FBLN1 3'UTR were identified. These findings might deepen our understanding of ECM gene regulatory networks and the complex etiology of AS.

Scalable multi-dimensional topological deformation actuators for active object identification.

Rarely are bionic robots capable of rapid multi-dimensional deformation and object identification in the same way as animals and plants. This study proposes a topological deformation actuator for bionic robots based on pre-expanded polyethylene and large flake MXene, inspired by the octopus predation behavior. This unusual, large-area topological deformation actuator (easily reaching 800 cm2 but is not constrained to this size) prepared by large-scale blow molding and continuous scrape coating exhibits different distribution states of molecular chains at low and high temperatures, causing the actuator's deformation direction to change axially. With its multi-dimensional topological deformation and self-powered active object identification capabilities, the actuator can capture objects like an octopus. The contact electrification effect assists the actuator to identify the type and size of the target object during this multi-dimensional topological deformation that is controllable and designable. This work demonstrates the direct conversion of light energy into contact electrical signals, introducing a new route for the practicality and scaling of bionic robots.

Thermopressure Coupling Effect Mimicking Natural Graphite Formation to Enhance the Storage K-Ion Performance of Carbonaceous Heterostructures.

Borrowing from natural mechanisms for material design can lead to functional mimicry and improvement. Inspired by graphite formation, a thermopressure coupling strategy under micropressure (<400 Pa) is applied to prepare carbon anodes. A thermopressure response is discovered based on the cellulose precursor. Here, homologous graphene quantum dot/hard carbon (GQD/HC) heterostructures are synthesized. Under 181.4 Pa and 1,200 °C, the product shows a capacity of 310 mAh g-1, while the capacity of the direct carbonization product is only 120 mAh g-1. Prominently, the GQD/HC heterostructure displays marked mechanical strength and flexibility. The experimental and theoretical results illustrate the ion and electron transfer, coordination environment, and electronic states in the GQD/HC heterostructure and elaborate on the origin of the enhanced performance. The thermopressure coupling under micropressure mimics graphite formation, but the heterostructure has better properties than traditional carbon materials. Additionally, micropressure injects new vitality into material research.

Anatomical segmentectomy under uniportal video-assisted thoracoscopic surgery for early staged non-small cell lung cancer: a case report.

Background: Anatomical segmentectomy has become more and more universal in thoracic surgery because of the increasing detection of pulmonary nodules with ground-glass opacity (GGO), most of which proved early staged non-small cell lung cancer (NSCLC) postoperative. With the advantage of preservation of normal lung tissues, segmentectomy may be performed by surgeons when computed tomography (CT) scan shows pure GGO or multiple GGOs appearing. Especially when the patients with poor cardiopulmonary function or severe comorbidities or in the circumstance of bilateral pulmonary GGOs, segmentectomy can provide opportunities to radically resect all lesions. With the development of minimally invasive surgery technology, uniportal video-assisted thoracoscopic surgery (VATS) has become the regular operative route in many medical centers because it can provide less access trauma, less stress response, less pain, shorter hospital stays, and a lower postoperative complication rate and corresponds well with the idea of "minimally invasive". However, all of the procedures must be performed in one tiny portal, so uniportal VATS anatomical segmentectomy not only needs the skill and patience of surgeons but the effective cooperation of assistants, nurses and anesthetists, and plenty of details must be paid special attention. Case Description: Here we present a video of a patient undergoing S1 segmentectomy of right upper lobectomy (RUL) under uniportal VATS. The chief complaints of the patients was that two pure GGOs in the bilateral upper lobe were found by physical examination for 26 months and he had no symptoms. We performed S1 segmentectomy of RUL under uniportal first time and performed trisegmentectomy of left upper lobectomy (LUL) 3 months later. With routinely follow-up, no evidence of relapse and metastasis disease was found. Conclusions: We think anatomical segmentectomy under uniportal VATS can be a feasible and safe procedure that reduces trauma and has equivalent oncology outcomes to lobectomy in early-stage lung cancer but need a more experienced medical center to perform. Keywords: Uniportal video-assisted thoracoscopic surgery (uniportal VATS); segmentectomy; non-small cell lung cancer (NSCLC); case report.

An old unicondylar tibial plateau fracture (Schatzker type III) with tibial shaft fracture: A case report.

Introduction: and importance: Unicondylar tibial plateau fractures with tibial shaft fractures are extremely rare among the elderly group of people. The traditional treatment method is to apply double plates to fix unicondylar tibial plateau fractures combined with tibial shaft fractures respectively, but this fixation method can disrupt the blood supply around the soft tissues and increase the rate of postoperative infection and fracture non-union. In this paper, we would analyse an old unicondylar tibial plateau fracture (Schatzker type III) with tibial shaft fracture which admitted to our department and discussed the efficacy of using intramedullary nails and plates in the treatment of these fractures. Case presentation: A 78-year-old woman with an old unicondylar tibial plateau fracture combined with tibial shaft fracture was presented in this case. Using an intramedullary nail combined with a plate to achieve good results. Clinical discussion: This case represents a rare case of an unicondylar tibial plateau fracture with a tibial shaft fracture. In this case, the tibial plateau fracture was first incised and internally fixed with a 9-hole plate across the fracture line of the tibial shaft, followed by fixing the tibial shaft fracture with an intramedullary nail. This treatment helped us successfully reset the unicondylar tibial plateau fracture with tibial shaft fracture and provided a satisfactory outcome for the patient. Conclusion: Using intramedullary nails combined with plates to treat unicondylar tibial plateau fractures with tibial shaft fractures allowed for a predictable healing result.

JAK-STAT signaling mediates the senescence of cartilage-derived stem/progenitor cells.

Aging is a major risk factor for degenerative joint diseases, such as osteoarthritis (OA). Previous studies have confirmed the link between senescent mesenchymal stem cells (MSCs) and OA. Cartilage-derived stem/progenitor cells (CSPCs) with MSCs properties have been extracted from a variety of species. We inferred that the senescence of CSPCs may promote the development of osteoarthritis. However, the cellular and molecular mechanisms of CSPCs senescence remains unknown. In this study, we investigated the role of JAK-STAT signaling pathway in a replicative senescence model of CSPCs. We showed that the late CSPCs (> 15th passage) exhibited distinct senescent phenotypes, including increased proportion of ß-gal positive senescent cells and F-actin content, as well as cell cycle arrest. In late CSPCs, the activity of JAK-STAT signaling pathway was significantly increased. Activation of JAK-STAT signaling pathway promoted cell senescence in early CSPCs (< 6th passage). Conversely, pharmacological inhibition or genetic knockdown of JAK-STAT signaling pathway attenuated cell senescence in late CSPCs. In conclusion, our results demonstrated the critical role of JAK-STAT signaling pathway in CSPCs senescence.

Pin1-mediated regulation of articular cartilage stem/progenitor cell aging.

Cartilage stem/progenitor cells (CSPCs) was recently isolated and identified from the cartilage tissue. CSPCs is essential for repair and regeneration of cartilage in osteoarthritis (OA). Aging is a primary risk factor for cartilage damage and joint OA. Although studies have confirmed the link between cell aging and OA, the underlying molecular mechanisms regulating CSPCs aging are not fully understood. In this study, we investigated the role of Pin1 in the aging of rat knee joint CSPCs. We isolated CSPCs from rat knee joints and demonstrated that, in long-term in vitro culture, Pin1 protein levels are significantly reduced. At the same time, expression of the senescence-related ß-galactosidase and the senescence marker p16INK4A were markedly elevated. In addition, Pin1 overexpression reversed the progression of cellular senescence, as evidenced by the down-regulation of senescence-related ß-galactosidase, increased EdU positive cells and diminished levels of p16INK4A. In contrast, Pin1 siRNA incorporation promoted CSPCs senescence. In addition, we also observed the distribution of cell cycles through flow cytometry and revealed that Pin1 deficiency results in cell cycle arrest in the G1 phase, suggesting severe lack of proliferation ability, a sign of cellular senescence. Collectively, these results validated that Pin1 is an essential regulator of CSPCs aging.

Effects of 8-week High-Intensity Interval Training and Moderate-Intensity Continuous Training on Bone Metabolism in Sedentary Young Females.

OBJECTIVE: High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been reported as effective exercise modes on bone metabolism. However, very few studies focused on young women with sedentary behavior. The purpose of this study was to investigate the effects of 8-week HIIT on bone metabolism in sedentary young women. METHODS: 26 healthy, sedentary female participants were randomly assigned to either the HIIT (n = 13, age 23.2 ± 2.9 yr, weight 59.2 ± 7.2 kg, height 162.9 ± 3.3 cm, body mass index 22.3 ± 2.7 kg/m2) or MICT (n = 13, age 21.9 ± 1.7 yr, weight 59.3 ± 6.6 kg, height 160.9 ± 4.4 cm, body mass index 21.6 ± 2.4 kg/m2) group. Both groups completed 8 weeks (3 sessions/week) of training on the treadmill, where the HIIT group were asked to complete 6 × 3-min bouts of running at the intensity of 80-90% maximum oxygen uptake (VO2max) separated by 2-min active recovery at 30-40% VO2max and the MICT group completed 30-min continuous running at the intensity of 60-70% VO2max. The body composition, bone mineral density (BMD), calcaneus quantitative ultrasound, bone turnover markers, and lower limb muscle strength were measured pre and post interventions. RESULTS: After 8-week interventions, 1) The total body BMD (HIIT, +8.5%; MICT, +5.5%) significantly increased (p < 0.05) without difference between the two groups (p > 0.05). The calcaneus broadband ultrasound attenuation (CBUA) (HIIT, +16.0%; MICT, +4.6%) and calcaneus stiffness index (CSI) (HIIT, +16.7%; MICT, +2.5%) significantly increased in HIIT group (p < 0.05), but not in MICT group (p > 0.05). 2) The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (HIIT, +42.8%; MICT, +24.9%) level increased in both groups with significantly higher changes in HIIT (p < 0.05). 3) The score of standing long jump (HIIT, +10.3%; MICT, +3.8%) and vertical jump (HIIT, +5.3%; MICT, +2.0%) increased in both groups with significantly higher changes in HIIT (p < 0.05). CONCLUSIONS: It suggested that 8-week HIIT and MICT interventions could improve bone metabolism. Compared with a similar workload of MICT, HIIT elicited superior benefits on bone metabolism.

Characterization and Evaluation of the Pro-Coagulant and Immunomodulatory Activities of Polysaccharides from Bletilla striata.

Bletilla striata is widely used for stanching bleeding. In this study, polysaccharides from B. striata (BSP) were extracted by hot water. Four polysaccharides named BSP-1-BSP-4 were fractionated using DEAE-52 cellulose. BSP fractions contained sulfate, and the degrees of substitution of BSP-3 and BSP-4 were 1.59 and 1.70, respectively. Analysis of monosaccharide composition showed that four polysaccharides were mainly composed of mannan and glucose. The in vitro results showed that BSP-1-BSP-4 elicited pro-coagulant capacities by shortening the activating partial thromboplastin time, prothrombin time, and thrombin time and elevating the fibrinogen content. Immunomodulatory activity was evaluated by MTT assay, the pinocytic capacity and NO production. Although BSP fractions did not affect RAW 264.7 cell viability, they, especially BSP-2, enhanced the immunomodulatory activity by increasing the pinocytic capacity and NO production. Overall, BSP may be developed as a potential coagulant with immunomodulatory effects.

Leveraging sequence-based faecal microbial community survey data to identify alterations in gut microbiota among patients with Parkinson's disease.

Parkinson's disease is a common degenerative disease of the elderly. Although the majority of studies have focused on the central nervous system (CNS) features of Parkinson's disease, recent findings suggest there is a functional link between the gut microbiome and the hallmarks of the disease. PubMed, Web of Science, EMBASE and other Chinese and English databases were searched for relevant literature. Studies on changes to intestinal microbiota in Parkinson's patients were retrieved and systematically reviewed. Quality filtering, clustering and species annotation were performed on 16s sequencing raw data from retrieved studies to achieve comparability across studies. Alpha-diversity indices and a random effect model were used to analyse significantly altered microbiota. A total of nine studies were included in this retrospective analysis, four of which contained raw data. Alpha diversity was significantly different between control and Parkinson's disease patients in two of the four studies. Using the raw data from four individual studies, we observed differences in the phlya Bacteroidetes and Actinobacteria. Additionally, differences were observed between control and Parkinson's disease patients at the level of family (Prevotellacaea and Lactobacillaceae) and genus (Bifidobacterium and Clostridium). This study confirmed that changes in the microbiome are a consistent feature of Parkinson's disease patients and, therefore, may contribute to the onset of disease.

Morita therapy for schizophrenia: An updated meta-analysis.

Morita therapy was developed for common mental problems, and our aim was to evaluate the clinical effect of Morita therapy on schizophrenia. The literature was searched in 10 databases, namely, PubMed, Chinese National Knowledge Infrastructure (CNKI), Sinomed, Wanfang, Cochrane Library, UpToDate, Web of Science, Medline, PsycINFO and Embase, from inception to September 4, 2019. Random-effects models were used. For continuous results, the standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated to synthesize the effects. Thirty studies were included, with a total of 2651 patients with schizophrenia. Compared to pharmacotherapy alone and standard care alone, Morita therapy plus pharmacotherapy and Morita therapy plus standard care both had significant effects on mental state (pooled effect size = -1.09, 95% CI: -0.35, -0.83), social functioning (pooled effect size = -0.61, 95% CI: -2.30, -0.92) and behavior (pooled effect size = 1.13, 95% CI: 0.75, 1.51). Significant heterogeneity between studies was found for mental state (I2 = 89%, p < 0.05) and social functioning (I2 = 95%, p < 0.05), but no heterogeneity was found for behavior (I2 = 0%, p = 0.84). Morita therapy has positive effects on mental state and social functioning among patients with schizophrenia, but it leads to some problems with behavior among these patients. Most included studies have unclear bias, and the forest plots show high heterogeneity among the results. Thus, Morita therapy cannot be implemented in clinical practice as a feasible strategy, the conclusion has yet to be confirmed, and new trials and future studies are desired.

Effect of high intensity interval training on cardiorespiratory fitness in sedentary female college students / 中国学校卫生

Objective@#The aim of this study was to observe the changes in cardiorespiratory fitness after high intensity interval training(HIIT), and to provide a reference basis for scientific and reasonable sports plans.@*Methods@#A total of 26 female college students with sedentary lifestyle were randomly allocated into MCT group (n=13) and HIIT group(n=13). All the participants undertook a graded exercise test to obtain VO 2max. The MCT group was trained with 60% VO 2max intensity for 30 min, while HIIT group received exercises with 90% VO 2max intensity every 3 min, intermittent 2 min, for 6 sessions three times a week for 8 weeks. Before and after 8 weeks of training, the subjects were tested for body shape, cardiorespiratory function and aerobic exercise capacity.@*Results@#BMI[(22.34±2.73)(21.56±2.39)kg/m2], percentage of body fat [(31.43±5.65)%, (28.85±5.52)%] of HIIT group and BMI [(22.98±3.23)(22.35±3.09)kg/m2], percentage of body fat [(33.15±4.48)%, (31.48±4.73)%] of MCT group showed significant changes before and after training(P<0.01). For cardiorespiratory function, there was a significant change in VC [(3.30±0.60)(3.61±0.54)L], vital capacity index(56.22±10.73, 63.51±10.53), and MVV [(81.44±20.45, 91.17±15.64)L/min] in HIIT group. There was also a significant change in VC [(3.08±0.41)(3.19±0.36)L] and vital capacity index (52.74±8.66, 55.62±7.88) in MCT group, and there was a significant difference between the two groups(P<0.01). In terms of aerobic exercise capacity, maximal oxygen uptake in HIIT group [(2 204.15±232.39)(2 539.23±339.39)mL/min] and MCT group [(2 136.15±240.76)(2 462.00±318.29)mL/min] increased significantly after training(P<0.01).@*Conclusion@#Both HIIT and MCT can significantly improve lung function and aerobic performance of sedentary female college students, but HIIT is found more effective than MCT training.

Effect of C-5 position on the photochemical properties and phototoxicity of antofloxacin and levofloxacin: A stable and transient study.

The photochemistry of two structure-related fluoroquinolones (FQs), antofloxacin (ANT) and levofloxacin (LEV), was studied in aqueous solution using stable and transient methods. The properties for energy transfer and electron transfer of these two FQs were also studied. The transient absorption spectra of FQs were observed, and transient species were assigned. The LEV triplet state ((3)LEV(⁎)) spectra (λmax = 610 nm) were determined, whereas the transient absorption of ANT could not be observed. The decay rate constant of (3)LEV(⁎) via unimolecular attenuation, self-quenching, and quenching by oxygen was 3.2 × 10(5) s(-1), 6.72 × 10(8) M(-1) s(-1), and 1.01 × 10(9) M(-1) s(-1), respectively. A reasonable diagram showing the decay of (1)FQs* consisting of various substituents at the C-5 position was proposed. The phototoxicity of LEV and ANT was investigated and compared. Insertion of an amino group at the C-5 position made ANT relatively photostable and non-phototoxic compared with LEV.

Seasonal variation of polybrominated diphenyl ethers in PM2.5 aerosols over the East China Sea.

PM2.5 aerosol samples were collected from a receptor site in the East China Sea (ECS) to explore the seasonal variation and sources of polybrominated diphenyl ethers (PBDEs). The concentrations of BDE-209 and total 11 PBDEs without BDE-209 (∑11PBDEs) were 7.1±6.8 and 0.97±0.52 pg m(-3), respectively. A distinct seasonal variation was observed for both BDE-209 and ∑11PBDEs, that higher concentrations in winter and spring dominated by the northwesterly winds while lower concentrations in autumn and summer when the southeasterly winds prevailed, suggesting a significant role of continental outflow on the elevated concentrations of PM2.5-bound PBDEs in winter and spring. Besides, the strong dust storm could increase the load of PBDEs in continental outflow to the atmosphere over ECS. Differently, due to the absence of continental outflow in autumn and summer, the good correlations between BDE-209 and ∑11PBDEs implied a potential contribution of the low brominated PBDEs from photoproducts of BDE-209 in high temperature circumstance, while the good correlations of OC with BDE-209 and BDE-99 suggested a significant role of OC in the occurrence of PM2.5-bound PBDEs over ECS.