Realizing asynchronous finite-time robust tracking control of switched flight vehicles by using nonfragile deep reinforcement learning.

In this study, a novel nonfragile deep reinforcement learning (DRL) method was proposed to realize the finite-time control of switched unmanned flight vehicles. Control accuracy, robustness, and intelligence were enhanced in the proposed control scheme by combining conventional robust control and DRL characteristics. In the proposed control strategy, the tracking controller consists of a dynamics-based controller and a learning-based controller. The conventional robust control approach for the nominal system was used for realizing a dynamics-based baseline tracking controller. The learning-based controller based on DRL was developed to compensate model uncertainties and enhance transient control accuracy. The multiple Lyapunov function approach and mode-dependent average dwell time approach were combined to analyze the finite-time stability of flight vehicles with asynchronous switching. The linear matrix inequalities technique was used to determine the solutions of dynamics-based controllers. Online optimization was formulated as a Markov decision process. The adaptive deep deterministic policy gradient algorithm was adopted to improve efficiency and convergence. In this algorithm, the actor-critic structure was used and adaptive hyperparameters were introduced. Unlike the conventional DRL algorithm, nonfragile control theory and adaptive reward function were used in the proposed algorithm to achieve excellent stability and training efficiency. We demonstrated the effectiveness of the presented algorithm through comparative simulations.

The clinical outcome of balloon-assisted maturation procedure between autogenous radiocephalic fistula and brachiocephalic fistula in a single-center experience.

OBJECTIVE: Balloon-assisted maturation (BAM) by an endovascular method plays an important role in treating an immature arteriovenous fistula. However, the results between radiocephalic fistula and brachiocephalic fistula were rarely reported. This retrospective study aimed to investigate the effectiveness and outcome of BAM in different sites of autogenous arteriovenous fistulas. METHODS: This single-center retrospective study included patients who underwent BAM procedures from January 2015 to December 2016. Of 148 patients, 117 and 31 patients had a radiocephalic fistula (RC) and a brachiocephalic fistula (BC), respectively. The primary outcome was BAM success. Data regarding fistula lesions, balloon types and size, frequency of procedures, and maturation time were collected for BAMs. The secondary outcome was the patency of a fistula in the follow-up period. RESULTS: No difference was observed in procedure of BAM frequency between the RC and BC groups. The total success rate was 77.7%, without significant difference between the RC and BC groups (81.20% vs 64.50%; P = .055). Within the procedures, the culprit lesion of juxta-anastomosis segment (73.5% vs 25.5%; P < .001) and arterial inlet (21.2% vs 7.8%; P = .04) were more common in the RC group, whereas the venous outlet was more common in the BC group (88.2% vs 57.7%; P < .001). Both groups had an equivalent patency rate after the BAM within the follow-up period (P = .272). CONCLUSIONS: BAM was an effective procedure for immature fistulas, without significant difference between RCs and BCs. Through the procedure, the culprit lesions causing non-maturation were found to be different between the two groups. The patency rate between the two groups after surgery seems to be equivalent within the follow-up period.

Diterpenoid Vinigrol specifically activates ATF4/DDIT3-mediated PERK arm of unfolded protein response to drive non-apoptotic death of breast cancer cells.

Vinigrol is a natural diterpenoid with unprecedented chemical structure, driving great efforts into its total synthesis in the past decades. Despite anti-hypertension and anti-clot ever reported, comprehensive investigations on bioactions and molecular mechanisms of Vinigrol are entirely missing. Here we firstly carried out a complete functional prediction of Vinigrol using a transcriptome-based strategy coupled with multiple bioinformatic analyses and identified "anti-cancer" as the most prominent biofunction ahead of anti-hypertension and anti-depression/psychosis. Broad cytotoxicity was subsequently confirmed on multiple cancer types. Further mechanistic investigation on several breast cancer cells revealed that its anti-cancer effect was mainly through activating PERK/eIF2α arm of unfolded protein response (UPR) and subsequent non-apoptotic cell death independent of caspase activities. The other two branches of UPR, IRE1α and ATF6, were functionally irrelevant to Vinigrol-induced cell death. Using CRISPR/Cas9-based gene activation, repression, and knockout systems, we identified the essential contribution of ATF4 and DDIT3, not ATF6, to the death process. This study unraveled a broad anti-cancer function of Vinigrol and its underlying targets and regulatory mechanisms. It paved the way for further inspection on the structure-efficacy relationship of the whole compound family, making them a novel cluster of PERK-specific stress activators for experimental and clinical uses.

Clinical outcomes of AngioJet rheolytic thrombectomy in the treatment of May-Thurner syndrome-related deep venous thrombosis.

OBJECTIVE: May-Thurner syndrome (MTS) is an anatomic stenotic variation associated with deep vein thrombosis (DVT) of the left leg. The classical DVT treatment strategy is medical treatment without thrombus removal. This study was performed to assess the clinical outcomes of the combination of AngioJet™ rheolytic thrombectomy and stenting for treatment of MTS-related DVT. METHODS: We conducted a retrospective cohort study of patients treated for MTS-related DVT from January 2017 to June 2020 at a single institution. RESULTS: Fourteen patients (nine women) underwent AngioJet™ rheolytic thrombectomy for MTS-related DVT during the study period. The median DVT onset time was 8 days (interquartile range (IQR), 3-21 days). The median procedure time was 130 minutes (IQR, 91-189 minutes), and the median hospital stay was 7 days (IQR, 5-26 days). One patient had a residual thrombus and occluded iliac stent and underwent adjuvant catheter-directed thrombolysis for revascularization. The primary patency rate for the iliac stent was 92.9% at 12 months. CONCLUSION: Concomitant AngioJet™ rheolytic thrombectomy and stenting of MTS-induced lesions may be beneficial for patients with MTS-related DVT.

The immunomodulatory effects of ginsenoside derivative Rh2-O on splenic lymphocytes in H22 tumor-bearing mice is partially mediated by TLR4.

PURPOSE: Previously, we reported the octyl ester derivative of ginsenoside Rh2 (Rh2-O) had better antitumor and immunomodulatory effects than Rh2 in H22 tumor-bearing mice. Therefore, this study further explored the effects of Rh2-O on splenic lymphocytes in H22 tumor-bearing mice and the underlying mechanism. METHODS: Wild type and Tlr4-/- mice were selected to establish the H22 tumor-bearing mice model. After the treatment of Rh2-O (10 mg/kg by gavage) for 15 days, the sizes of tumor were measured. Subsequently, the splenic lymphocytes were isolated and the activities (eg. cell proliferation, cytotoxicity and cytokine secretion) were evaluated. Then, the proteins and mRNA expression levels of TRAF6 and NF-ĸB p65 in splenic lymphocytes were examined. RESULTS: The results showed that Rh2-O administration enhanced the proliferative capacity and cytotoxicity of splenic lymphocytes, and the effects were Tlr4-associated. Compared to WT mice, the up-regulation of cytokines secretion (eg. IFN-γ, IL-2 and IL-4) in isolated splenic lymphocytes after Rh2-O administration was lower in Tlr4-/- mice. Moreover, the results showed Rh2-O increased the expression of TRAF6 and the level of endonuclear NF-ĸB p65, which was inhibited in Tlr4-/- mice (P < 0.05). CONCLUSION: Rh2-O could exert immunomodulatory effects on splenic lymphocytes with the partial participation of TLR4 in H22 tumor-bearing mice.

CASB: a concanavalin A-based sample barcoding strategy for single-cell sequencing.

Sample multiplexing facilitates single-cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost-effective strategies are rather limited. Here, we reported a concanavalin A-based sample barcoding strategy (CASB), which could be followed by both single-cell mRNA and ATAC (assay for transposase-accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, and high sensitivity in detecting doublets by three applications: 1) CASB followed by scRNA-seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound-specific heterogeneous response; 2) CASB together with both snATAC-seq and scRNA-seq to illustrate the IFN-γ-mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN-γ response; and 3) combinatorial indexing by CASB, which demonstrated its high scalability.

Comparison between Totally Percutaneous Approach and Femoral Artery Cut-Down in Endovascular Aortic Repair of Ruptured Abdominal Aortic Aneurysms in a Single Hospital.

PURPOSE: To evaluate the short-term outcome of totally percutaneous endovascular aortic repair (pEVAR) of ruptured abdominal aortic aneurysms (AAAs) compared with femoral cut-down endovascular aortic repair (cEVAR). MATERIALS AND METHODS: The medical records of patients with ruptured AAAs that underwent EVAR between March 2010 and April 2017 were retrospectively reviewed. Demographic information, preoperative vital signs, preoperative laboratory data, method of anesthesia, procedure duration, aneurysm morphology, brand of device used, length of hospital stay, access complications, and short-term outcomes were recorded. Univariate as well as multivariate logistic regression was used to identify predictors of 30-day mortality. RESULTS: Among 77 patients with ruptured AAAs, 17 (22.1%) received cEVAR and 60 (77.9%) received pEVAR. Significant differences in the procedure time (P = 0.004), method of anesthesia (P = 0.040), and 30-day mortality (P = 0.037) were detected between the cEVAR and pEVAR groups. Local anesthesia plus intravenous general anesthesia (odds ratio = 0.141, P = 0.018) was an independent factor associated with 30-day mortality and local anesthesia was better than general anesthesia for 24-hr mortality (P = 0.001) and 30-day mortality (P = 0.003). CONCLUSION: In patients with ruptured AAAs, pEVAR procedures took less time than cEVAR procedures, but the length of hospital stay did not differ significantly. The 30-day mortality rate was lower with pEVAR than with cEVAR. Local anesthesia may be the key factor in EVAR to improved technical and clinical success.

Total Resection of Infected Peripheral Hemodialysis Grafts Has a Favorable Impact on Outcomes.

BACKGROUND: Surgical resection could be an eradication treatment for patients with infected hemodialysis arteriovenous grafts (AVGs). This study aimed to investigate the outcomes of 3 surgical methods, including total resection, subtotal resection, and revision. METHODS: The patients who underwent surgical excision of infected AVGs performed at a single center from August 2012 to March 2019 were retrospectively analyzed. The following 3 surgical methods were used in our study: revision, subtotal resection, and total resection. Patients' demographics, medical history, perioperative details, reconstruction time, and follow-up data were collected. The outcomes including perioperative complications (within 30 days), mortality, reinfection rate of AVGs, with new access reconstruction or not, and the outcomes between reconstruction and nonreconstruction in the follow-up period were evaluated. RESULTS: Forty-one patients had infected AVGs in our study. Patients' mean age was 62 years, and 65.9% of the patients were female. The mean duration from the time of diagnosis to the operation was 14.4 days. Signs and symptoms at presentation included fever (51.2 %), swelling (43.9%), pain (58.5%), erythematous change (92.7%), and more severe features, such as altered consciousness (14.6%) and hypotension (12.2%). The pathological changes in the infected grafts included bleeding (29.3%), pus formation (73.2%), pseudoaneurysm (26.8%), and graft exposure (17.1%). Wound and graft cultures revealed an infectious etiology with fungi (7.3%), Pseudomonas aeruginosa (12.2%), Enterococcus spp. (2.4%), and Staphylococcus spp. (58.5%), with methicillin-resistant Staphylococcus aureus accounting for only 7.3%. Total resection, subtotal resection, and revision surgery were performed in 17.1%, 63.4%, and 19.5% of patients, respectively. Seven patients with complications required reoperation (17.1%), and adhesion ileus and hospital-acquired pneumonia occurred in only 2.4% and 7.3% of patients, respectively. During follow-up, most patients (82.9%) had reconstruction of the peripheral hemodialysis access with mean time of 64.3 (range: 21-92) days; mean time of use of new access was 90.5 days; and mean time of removal of catheter was about 106.3 days. Mortality rates in patients without and with reconstructed AV access during follow-up were 50% and 18%, respectively (P < 0.004). Eight cases (19.5%) had recurrence of AV access infections during follow-up; of these, 2 had revision surgery and 6 had subtotal resection. However, no patient with total resection had recurrent infections. CONCLUSIONS: The total resection group had no recurrent infection compared to the subtotal and revision groups. In addition, patients with reconstruction of peripheral hemodialysis access had a low mortality rate during the follow-up period.

Proximity labeling to detect RNA-protein interactions in live cells.

RNA biology is orchestrated by the dynamic interactions of RNAs and RNA-binding proteins (RBPs). In the present study, we describe a new method of proximity-dependent protein labeling to detect RNA-protein interactions [RNA-bound protein proximity labeling (RBPL)]. We selected the well-studied RNA-binding protein PUF to examine the current proximity labeling enzymes birA* and APEX2. A new version of birA*, BASU, was used to validate that the PUF protein binds its RNA motif. We further optimized the RBPL labeling system using an inducible expression system. The RBPL (λN-BASU) labeling experiments exhibited high signal-to-noise ratios. We subsequently determined that RBPL (λN-BASU) is more suitable than RBPL (λN-APEX2) for the detection of RNA-protein interactions in live cells. Interestingly, our results also reveal that proximity labeling is probably capable of biotinylating proximate nascent peptide.

Protective effects of wedelolactone on dextran sodium sulfate induced murine colitis partly through inhibiting the NLRP3 inflammasome activation via AMPK signaling.

It has been reported that the ethanol extract of Wedelia chinensis attenuates murine colitis. Wedelolactone (WEL), a coumestane-type compound with many pharmacological activities, was isolated from W. chinensis. The present study aims to investigate the beneficial effects and underlying mechanisms of WEL on ulcerative colitis. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of WEL (50mg/kg) significantly attenuated pathological colonic damage and inhibited inflammatory infiltration, myeloperoxidase and alkaline phosphatase activities through MAPKs and NF-κB signaling pathways, while activating AMPK in colons treated with DSS. Further study revealed that WEL treatment dramatically inhibited NLRP3 inflammasome activation and caspase-1 phosphorylation to decrease IL-1ß release in colons treated with DSS. In addition, WEL effectively regulates the disorder of skeleton proteins in colonic epithelial cells NCM460 exposed to TNF-α and protects the intestinal barrier function by activating AMPK in vivo. In summary, the AMPK-NLRP3-IL-1ß signaling axis plays an important role in colitis following WEL treatments. These findings provide new insights into the pharmacological actions of WEL as a potential therapeutic agent for colitis.

Protective role of rhapontin in experimental pulmonary fibrosis in vitro and in vivo.

BACKGROUND: Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated. METHODS: The effect of rhapontin on TGF-ß1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-ß1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo. Fibrotic mice were induced by intratracheal instillation of bleomycin, and then treated with rhapontin (25, 50, or 100mg/kg/day) or prednisone (6.5mg/kg/day, positive drug) for 2weeks. RESULTS: In TGF-ß1 stimulated PLFs, treatment with rhapontin resulted in a reduction of ECM with a decrease in Lox2 and p-Smad2/3. In LPS activated macrophages, treatment with rhapontin reduced TGF-ß1 production. However, in vitro the attenuated ECM deposition and inflammatory response by rhapontin were closely associated with AMPK activation, and these suppression of rhapontin were significantly abolished by the AMPK inhibitor. Treatment with rhapontin for 2weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower Lox2, whereas a higher AMPK expression, with reductions of the pathological score, collagen deposition, TGF-ß1, α-SMA, Lox2, and HIF-1α expressions in lung tissues at fibrotic stage at 100mg/kg. CONCLUSION: In summary, rhapontin reversed ECM, as well as Lox2 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating AMPK activation and suppressing the TGF-ß/Smad pathway.

Rhapontin ameliorates colonic epithelial dysfunction in experimental colitis through SIRT1 signaling.

Rhapontin (3, 3', 5-trihydroxy-4'-methoxystilbene-3-O-glucoside) has anti-thrombotic, anti-allergic and anti-diabetic activities. This study aimed to assess the protective effects of rhapontin on intestinal damage in vivo and in vitro. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of rhapontin (100mg/kg) significantly attenuated colonic pathological damage and remarkably inhibited infiltration by inflammatory cells, myeloperoxidase (MPO) activity, NLRP3 inflammasome activation and SIRT1 expression in the colon. Moreover, rhapontin prevented DSS-induced impairment in the colon epithelium barrier by increasing the expression of tight junction proteins, such as zonula occludens-1(ZO-1) and occludin, and reduced apoptosis-associated protein (cyt-c, the ratio of bcl-2/bax and cleaved-capase9) expression in the colon. The in vitro results showed that rhapontin significantly reduced NLRP3 inflammasome activation and cleaved caspase-1 expression as well as lowered IL-1ß secretion in LPS-stimulated human-THP-1-derived macrophages. Further study revealed that compound EX257 (an SIRT1 inhibitor) blocked the inhibitory effects of rhapontin on NLRP3-dependent caspase-1 activation and IL-ß production in activated macrophages. In addition, in TNF-α-stimulated intestinal epithelial NCM460 cells, rhapontin significantly increased the expressions of occludin and ZO-1 and notably reduced the ratio of bcl-2/bax and cleaved-capase9 expression through SRIT1 signaling. In sum, the protective effect of rhapontin is from blocking the NLRP3 priming cascade reaction and is dependent on SIRT1 activation. Our findings demonstrate that rhapontin might be a potential agent for the treatment of colitis by targeting SIRT1.

Synthesis and Study on Ionic Conductive (Bi1-x,Vx)O1.5-δ Materials with a Dual-Phase Microstructure.

Homogeneous Bi2O3-V2O5 powder mixtures with different amounts of V2O5 content (≤15 mol%) were prepared by colloidal dispersion and sintering to high density. The sintered and annealed samples were studied by thermal analysis, quantitative X-ray diffraction and scanning electron microscopy. The electrical and ionic conductivities of the conductors were also measured by a four-probe direct current (DC) method. The results of the samples prepared at 600-800 °C and annealed for as long as 100 h show that the sintered samples consisting of a pure γ phase or δ + γ binary phase perform differently in conductivity. The highly conductive δ phase in the composition of Bi0.92V0.08O1.5-δ enhances the electric conductivity 10-times better than that of the pure γ-sample (Bi0.94V0.06O1.5-δ) between 400 and 600 °C. The compatible regions of the γ phase with the α- or δ phase are also reported and discussed, so a part of the previously published Bi2O3-V2O5 phase diagram below 800 °C is revised.

(Bi,Sr) (Fe1-x,Mx)O3-δ (M = Co, Ni and Mn) Cathode Materials with Mixed Electro-Ionic Conductivity.

(Bi,Sr)FeO3-δ (BSF) cathode materials doped with either Co, Ni or Mn are synthesized by an ethylene diamine tetra-acetic acid (EDTA)-citrate complexing method, and the effects of the doping level on the mixed electronic-ionic conductivity at various temperatures are studied up to 800 °C. The phase purity and solid solution limit are investigated by X-ray diffraction (XRD). The ionic conductivity is measured by the four-probe direct current (DC) method, the valence state of Fe and Mn by X-ray photoelectron spectroscopy (XPS), and the oxygen non-stoichiometry by differential thermo-gravimetric analysis (TGA). The doped ferrites show interesting electronic conductivity dependent on the testing temperature, implying two conductive mechanisms, either controlled by double exchange at lower temperatures or small polaron (electron-oxygen vacancy) conduction at temperatures greater than 400 °C. The results of Co-doped BSF (S50C20) show the best mixed conductivity among the ferrites, and this is used to assemble cells. The cell with a S50C20 cathode in the region of 600-800 °C is improved by 15% in maximum power density greater than the cell with La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) due to the balanced contribution from oxygen ions, vacancies and electrons.

The Treatment Results of a Standard Algorithm for Choosing the Best Entry Vessel for Intravenous Port Implantation.

Vascular cutdown and echo guide puncture methods have its own limitations under certain conditions. There was no available algorithm for choosing entry vessel. A standard algorithm was introduced to help choose the entry vessel location according to our clinical experience and review of the literature. The goal of this study is to analyze the treatment results of the standard algorithm used to choose the entry vessel for intravenous port implantation.During the period between March 2012 and March 2013, 507 patients who received intravenous port implantation due to advanced chemotherapy were included into this study. Choice of entry vessel was according to standard algorithm. All clinical characteristic factors were collected and complication rate and incidence were further analyzed.Compared with our clinical experience in 2006, procedure-related complication rate declined from 1.09% to 0.4%, whereas the late complication rate decreased from 19.97% to 3.55%. No more pneumothorax, hematoma, catheter kinking, fractures, and pocket erosion were identified after using the standard algorithm. In alive oncology patients, 98% implanted port could serve a functional vascular access to fit therapeutic needs.This standard algorithm for choosing the best entry vessel is a simple guideline that is easy to follow. The algorithm has excellent efficiency and can minimize complication rates and incidence.