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Objective: Response surface methodology was used to optimize the extraction process of steroidal glycosides from Cynanchum auriculatum Royle ex Wight by complex enzymatic method, and its effects on alcohol dehydrogenase activity and human hepatoma cell HepG2 were analyzed. Methods: Four experimental factors; enzymolysis duration, temperature, compound enzyme dose and pH were used as responses to a single-factor experiment of the Response Surface Methodology on the steroidal glycoside yields, using perennial C. auriculatum as the target material. The alcohol-induced hepatocyte damage model of HepG2 was used to investigate the contents of ALT, LDH, and GSH and changes in cell shape. Results: The results show that the optimum extraction conditions of steroidal glycoside enzyme were obtained at an enzymolysis duration of 100 min, a temperature of 46 ℃, enzyme dose of 1.30% and pH of 5.0. Consequently, the actual extraction rate of （2.80±0.04）% was achieved using the optimized process conditions, which was close to the expected value. Compared with the model group, it significantly suppresses the growth of ALT and LDH while increasing the amount of intracellular GSH, and the cell damage was restored. Conclusion: The compound enzyme method can effectively extract the steroidal glycosides of Cynanchum auriculatum Royle ex Wight; steroidal glycosides of C. auriculatum have hepatoprotective effect.

Introduction: Atherosclerotic complications represent the leading cause of cardiovascular mortality globally. Dysfunction of endothelial cells (ECs) often initiates the pathological events in atherosclerosis. Objectives: In this study, we sought to investigate the transcriptional profile of atherosclerotic aortae, identify novel regulator in dysfunctional ECs and hence provide mechanistic insights into atherosclerotic progression. Methods: We applied single-cell RNA sequencing (scRNA-seq) on aortic cells from Western diet-fed apolipoprotein E-deficient (ApoE−/−) mice to explore the transcriptional landscape and heterogeneity of dysfunctional ECs. In vivo validation of SOX4 upregulation in ECs were performed in atherosclerotic tissues, including mouse aortic tissues, human coronary arteries, and human renal arteries. Single-cell analysis on human aortic aneurysmal tissue was also performed. Downstream vascular abnormalities induced by EC-specific SOX4 overexpression, and upstream modulators of SOX4 were revealed by biochemical assays, immunostaining, and wire myography. Effects of shear stress on endothelial SOX4 expression was investigated by in vitro hemodynamic study. Results: Among the compendium of aortic cells, mesenchymal markers in ECs were significantly enriched. Two EC subsets were subsequently distinguished, as the ‘endothelial-like’ and ‘mesenchymal-like’ subsets. Conventional assays consistently identified SOX4 as a novel atherosclerotic marker in mouse and different human arteries, additional to a cancer marker. EC-specific SOX4 overexpression promoted atherogenesis and endothelial-to-mesenchymal transition (EndoMT). Importantly, hyperlipidemia-associated cytokines and oscillatory blood flow upregulated, whereas the anti-diabetic drug metformin pharmacologically suppressed SOX4 level in ECs. Conclusion: Our study unravels SOX4 as a novel phenotypic regulator during endothelial dysfunction, which exacerbates atherogenesis. Our study also pinpoints hyperlipidemia-associated cytokines and oscillatory blood flow as endogenous SOX4 inducers, providing more therapeutic insights against atherosclerotic diseases.

Tricuspid regurgitation (TR) may occur late after left-sided valve surgery (LSVS). Isolated tricuspid regurgitation after left-sided valve surgery (iTR-LSVS) refers to isolated TR without significant lesions in the mitral and/or aortic position late after mitral and/or aortic replacement or repair. Severe TR has a negative impact on long-term prognosis and requires surgical or transcatheter treatment. However, there is no clear recommendation on when and how intervention should be performed for patients with iTR-LSVS in the current guidelines for the management of valvular heart disease. The historically high operative mortality may be reduced by current minimally invasive techniques and transcatheter therapy. To further understand iTR-LSVS, standardize the treatment, improve the prognosis, and promote the collaboration, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) wrote this expert consensus on the management of iTR-LSVS from the aspects of etiology, preoperative evaluation, indications for intervention, surgical treatment, transcatheter therapy, and postoperative management.

Abstract Background Hepatitis B virus (HBV) infection is difficult to cure. HBV-specific immune tolerance plays a key role in HBV persistence, and enhancing cellular and humoral immunity will improve the control of HBV infection. The purpose of the study was to explore the anti-HBV and immunostimulatory effects of msiRNAs that introduce unpaired uridine bulges in the passenger strand. Methods msiRNAs targeting the HBV S and X genes were designed and named msiHBs and msiHBx, respectively. HepG2 cells were cotransfected with siRNA or msiRNA and the HBV replication-competent plasmid pHY106-wta or pHY106-X15. HepG2.215 cells were transfected with siRNA or msiRNA. The levels of HBsAg, HBeAg, and the cytokines TNF-α, IFN-α, IFN-β, IL-1α, and IL-6 in the culture supernatant was detected by ELISA. The levels of intracellular HBV RNA, nuclear HBV replication intermediates, and HBV DNA in the supernatant were measured by quantitative RT-PCR and PCR. The levels of HBV replication intermediates were detected by Southern blotting. Peripheral blood mononuclear cells were transfected with siRNA or msiRNA, and the levels of secreted cytokines IFN-α and IFN-β were detected by ELISA. The bioactivity of type I interferons in the supernatants was detected by the virus protection assay. Results msiHBx treatment led to a significant decrease in HBsAg (to a negative level) and HBV DNA (95.5%) in the supernatant and intrahepatocellular HBV replication intermediates (89.8%) in HepG2 cells with transient HBV replication and in HepG2.2.15 cells. There was no significant difference between msiHBx and siHBx in terms of the reduction in HBV proteins and HBV replication (P > 0.05). Compared with siHBx, msiHBx treatment of HepG2 cells transfected with the HBV replication-competent plasmid led to a significant increase in the levels of the antiviral cytokines TNF-α (3.3-fold), IFN-α (1.4-fold), and IFN-β (2.5-fold) (P

The effect of cold temperature on Electric Vehicle (EV) was investigated on an A class sedan through theoretical and experimental tests. Under cold weather, the drive range was reduced by 42.8% due to reasons such as the energy consumption of cabin heating, the reduction of electric energy capacity of battery and a reduction of efficiency of Electric Drive System (EDS). The cabin heating system is the biggest contributor for the reduction of drive range under cold temperature. Unlike the conventional vehicle where the engine waste heat is recycled, a Positive Temperature Coefficient (PTC) heater which directly withdraws electric energy from battery is used as the heat source for EV. This results in a reduction of EV range. Two approaches that can reduce the energy consumption of cabin heating system were investigated, namely the adoption of Intelligent Air Recirculation (IAR) and Heat Pump (HP). IAR and HP brought an increase of EV range under −7°C NEDC by 7.1%–7.9%, respectively. Another factor that causes range reduction is the deterioration of electric energy capacity of battery. To mitigate this adverse influence, research was conducted on two approaches: Motor Heat Recycle System (MHRS) and Active Motor Heat Control (AMHC). The adoption of MHRS system could improve the EV range by 7.9% while AMHC yielded an improvement of range by 2.1%. When the temperature decreases, the system efficiency of EDS decreases. One reason is the increase of oil splash loss as the oil viscosity increases under cold temperature. Hence, one type of oil with lower viscosity was tested and the results showed that the EDS efficiency could be improved by 1.5% which accounted for a 2.2% increase in driving range. With these measures implemented onto the test vehicle, the EV range under cold temperature −7°C NEDC could be improved by 26.5%.

Background: Accumulating lines of evidence demonstrated that diabetic retinopathy (DR) patients trigger abnormalities in brain’s functional connectivity (FC), whereas the alterations of interhemispheric coordination pattern occurring in DR are not well understood. Our study was to investigate alterations of interhemispheric coordination in DR patients.Methods: Thirty-four DR individuals (19 males and 15 females: mean age: 52.97 ± 8.35 years) and 37 healthy controls (HCs) (16 males and 21 females; mean age: 53.78 ± 7.24 years) were enrolled in the study. The voxel-mirrored homotopic connectivity (VMHC) method was conducted to investigate the different interhemispheric FC between two groups. Then, the seed-based FC method was applied to assess the different FCs with region of interest (ROI) in the brain regions of decreased VMHC between two groups.Results: Compared with HC groups, DR groups showed decreased VMHC values in the bilateral middle temporal gyrus (MTG), lingual/calcarine/middle occipital gyrus (LING/CAL/MOG), superior temporal gyrus (STG), angular (ANG), postcentral gyrus (PosCG), inferior parietal lobule (IPL), and precentral gyrus (PreCG). Meanwhile, altered FC includes the regions of auditory network, visual network, default mode network, salience network, and sensorimotor network. Moreover, a significant positive correlation was observed between the visual acuity-oculus dexter (OD) and zVMHC values in the bilateral LING/CAL/MOG (r = 0.551, p = 0.001), STG (r = 0.426, p = 0.012), PosCG (r = 0.494, p = 0.003), and IPL (r = 0.459, p = 0.006) in DR patients.Conclusion: Our results highlighted that DR patients were associated with substantial impairment of interhemispheric coordination in auditory network, visual network, default mode network, and sensorimotor network. The VMHC might be a promising therapeutic target in the intervention of brain functional dysfunction in DR patients.

In this paper, we propose a novel mechanism for QR code security anti-counterfeit based on the fusion of visual secret sharing (VSS) and QR code (called VSSQR scheme), which can greatly improve the security of QR code payment. Due to different application scenarios, the background security anti-counterfeit application and the prospects security anti-counterfeit application are shown for QR code payment authentication. The basic idea of the two applications can be characterized as follows. First, two QR code shares that contain the information of the merchant can be generated based on VSSQR scheme with an original secret image. Second, the secret image can be revealed by stacking two QR code shares to obtain the original information. Finally, whether the stacking result is the same as the original secret image or not can determine the authenticity of QR code share used for payment. The analyses show the security of our method. The applications are conducted to show the effectiveness and practicability.

This article elaborates on cardioprotective action of hypothermia related long noncoding RNA against myocardial infarction through improving mitochondrial function, which preset by J Zhang. Herein, we provide the materials and methods used in that study. And provided the detail of dysregulation of lncRNAs under the treatment of hypothermia. Furthermore, we found that lnc-UIHTC (lncRNA upregulated in hypothermia treated cardiomyocyte, NONHSAT094064) attenuated cardiomyocytes apoptosis in vitro.

The master DNA damage repair histone protein, H2AX, is essential for orchestrating the recruitment of downstream mediator and effector proteins at damaged chromatin. The phosphorylation of H2AX at S139, γH2AX, is well-studied for its DNA repair function. However, the extended C-terminal tail is not characterized. Here, we define the minimal motif on H2AX for the canonical function in activating the MDC1-RNF8-RNF168 phosphorylation-ubiquitination pathway that is important for recruiting repair proteins, such as 53BP1 and BRCA1. Interestingly, H2AX recruits 53BP1 independently from the MDC1-RNF8-RNF168 pathway through its evolved C-terminal linker region with S139 phosphorylation. Mechanistically, 53BP1 recruitment to damaged chromatin is mediated by the interaction between the H2AX C-terminal tail and the 53BP1 Oligomerization-Tudor domains. Moreover, γH2AX-linker mediated 53BP1 recruitment leads to camptothecin resistance in H2AX knockout cells. Overall, our study uncovers an evolved mechanism within the H2AX C-terminal tail for regulating DNA repair proteins at damaged chromatin.

The basic theories of load forecasting on the power system are summarized. Fractal theory, which is a new algorithm applied to load forecasting, is introduced. Based on the fractal dimension and fractal interpolation function theories, the correlation algorithms are applied to the model of short-term load forecasting. According to the process of load forecasting, the steps of every process are designed, including load data preprocessing, similar day selecting, short-term load forecasting, and load curve drawing. The attractor is obtained using an improved deterministic algorithm based on the fractal interpolation function, a day’s load is predicted by three days’ historical loads, the maximum relative error is within 3.7%, and the average relative error is within 1.6%. The experimental result shows the accuracy of this prediction method, which has a certain application reference value in the field of short-term load prediction.

The proven safety and efficacy of minimal access video-assisted thoracic surgery has changed the way that spontaneous pneumothorax is managed. This review presents some of the experiences of the decade, discusses the controversies and reviews the current video-assisted thoracic surgical management of spontaneous pneumothorax.

BackgroundStatins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.MethodsPig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca(2+)]i, [ATP]i and [glucose]o uptake measurements.ResultsThe cromakalim (10 nM to 10 µM)- and pinacidil (10 nM to 10 µM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM). Simvastatin (1, 3 and 10 µM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 µM)- and pinacidil (10 µM)-mediated opening of whole-cell KATP channels of arterial myocytes. Simvastatin (10 µM) and AICAR (1 mM) elicited a time-dependent, compound C (1 µM)-sensitive [(3)H]-2-deoxy-glucose uptake and an increase in [ATP]i levels. A time (2-30 min)- and concentration (0.1-10 µM)-dependent increase by simvastatin of p-AMPKα-Thr(172) and p-PP2A-Tyr(307) expression was observed. The enhanced p-AMPKα-Thr(172) expression was inhibited by compound C, ryanodine (100 µM) and KN93 (10 µM). Simvastatin-induced p-PP2A-Tyr(307) expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 µM), and in [glucose]o-free or [Na(+)]o-free conditions.ConclusionsSimvastatin causes ryanodine-sensitive Ca(2+) release which is important for AMPKα-Thr(172) phosphorylation via Ca(2+)/CaMK II. AMPKα-Thr(172) phosphorylation causes [glucose]o uptake (and an [ATP]i increase), closure of KATP channels, and phosphorylation of AMPKα-Thr(172) and PP2A-Tyr(307) resulted. Phosphorylation of PP2A-Tyr(307) occurs at a site downstream of AMPKα-Thr(172) phosphorylation.

Background. Angiogenic factors following oncological surgery is important in tumor recurrence. Vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang-1), Ang-2, soluble VEGF-receptor 1 (sVEGFR1) and sVEGFR2 may influence angiogenesis. This prospective study examined the influence of open and video-assisted thoracic surgery (VATS) lung resections for early stage non-small cell lung cancer (NSCLC) on postoperative circulating angiogenic factors. Methods. Forty-three consecutive patients underwent major lung resection through either VATS (𝑛=23) or Open thoracotomy (𝑛=20) over an 8-month period. Blood samples were collected preoperatively and postoperatively on days (POD) 1 and 3 for enzyme linked immunosorbent assay determination of angiogenic factors. Results. Patient demographics were comparable. For all patients undergoing major lung resection, postoperative Ang-1 and sVEGFR2 levels were significantly decreased, while Ang-2 and sVEGFR1 levels markedly increased. No significant peri-operative changes in VEGF levels were observed. Compared with open group, VATS had significantly lower plasma levels of VEGF (VATS 170±93 pg/mL; Open 486±641 pg/mL; 𝑃=0.04) and Ang-2 (VATS 2484±1119 pg/mL; Open 3379±1287 pg/mL; 𝑃=0.026) on POD3. Conclusions. Major lung resection for early stage NSCLC leads to a pro-angiogenic status, with increased Ang-2 and decreased Ang-1 productions. VATS is associated with an attenuated angiogenic response with lower circulating VEGF and Ang-2 levels compared with open. Such differences in angiogenic factors may be important in lung cancer biology and recurrence following surgery.

Pulmonary infection caused by the opportunistic organisms Penicillium marneffei and Stenotrophomonas maltophilia in patients with Job’s syndrome is rare and not well documented. The case of a 30-year-old man with Job’s syndrome who developed recurrent pneumonia and lung abscesses caused by P marneffei and S maltophilia, complicated by massive hemoptysis, is described. Bronchial artery embolization was successful in controlling the hemoptysis; however, the infection proved fatal despite appropriate antimicrobial therapy. A brief review of the literature on Job’s syndrome and its associated infective pulmonary manifestations is also presented.