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This letter proposes a behavioral model to estimate the statistical photon arrival time for time-of-flight (TOF) measurement circuit simulation. A theoretical model is derived to calculate the photon arrival rate by full consideration of a variety of properties of a TOF measurement system, such as laser source, optics, single-photon avalanche diode detector, target distance, and ambient illumination. For the first time, the newly developed model is implemented in behavioral Verilog-A hardware description language and successfully operated on Cadence Spectre simulator for TOF circuit simulation. It is capable of accurately predicting the statistical performance parameters such as photon arrival time and achievable distance, providing a new candidate tool for the ease of design and simulation of various high-performance TOF measurement circuits.

Timing jitter as a key performance of single-photon avalanche diode (SPAD) detectors plays a significant role in determining the fast temporal response behavior of the SPAD device. Nevertheless, few analytic models are developed to directly calculate the characteristic of timing jitter for its modeling difficulty. In this paper, we propose a simple analytic modeling method, which can predict the temporal response of SPADs, without using time-consuming Monte Carlo simulation. Model investigation incorporates avalanche current, avalanche buildup time, and jitter tail under different conditions. Furthermore, the key model parameters provided by Geiger mode technology computer-aided design simulation allow an accurate prediction on timing jitter. Analytical results indicate that for an SPAD device structure with a shallow P+/N-well junction in a 0.18-μm CMOS technology, the Gaussian peak response with about 110-ps full-width at half-maximum and the exponential jitter tail are in good agreement with the measured data, validating the accuracy, and feasibility of this modeling method.

In most of resolver-to-digital converters, it is necessary to detect the sinusoidal and cosinusoidal envelopes of rotor angle position from the amplitude-modulated signals the resolver outputs. Conventional synchronous envelope detection methods usually adopt a microprocessor to generate excitation signal and sample resolver signals, which is easy to ensure the synchronization of sampling. However, these methods may result in too large consumption of microprocessor resources, especially when the excitation frequency is very high. In order to reduce the burden of the microprocessor, external excitation can be used instead, and the synchronization pulse for sampling trigger can usually be generated by comparing the externally generated carrier with a reference through comparison circuit. However, the unexpected factors in hardware may cause deviations of the synchronization pulse instants and thus affect the accuracy of the detected envelopes. In order to solve this problem, a novel strategy of synchronous envelope detection by using hardware circuits is proposed in this paper. First, error propagation of the unexpected factors to the synchronization pulse is minimized by optimizing the reference voltage for the comparison circuit. Second, the effects of the synchronization pulse instant deviations on the accuracy of the detected envelopes are minimized by optimizing the sampling phase of the resolver signals. Theoretical analysis indicates that high-accuracy synchronous envelope detection can be realized since the minimum effects of unexpected factors. Experimental results support the conclusion of theoretical analysis, and prove the effectiveness and feasibility of the proposed strategy.

The attitude stabilization of flexible spacecraft is significantly affected by environmental disturbances, elastic vibration of flexible appendages, and model uncertainties. These disturbances and uncertainties can be accurately estimated by the extended disturbance observer (EDO). However, the EDO is sensitive to measurement noise when high-order and large bandwidth are chosen. Thus, the output of the EDO will contain too much high-frequency noise which can degrade the attitude stability of the spacecraft and cause heavier chattering of the actuators. In order to suppress the effect of measurement noise, a noise reduction EDO (NREDO) is proposed in this paper. First, a dynamical model of disturbance is reconstructed by augmenting the integral of the virtual measurement of the lumped disturbance as a new state. Second, the NREDO is designed by utilizing the estimation error of the augmented state to update the observer estimates. Thereafter, the disturbance estimation accuracy is analyzed for the EDO and NREDO in the frequency domain in the presence of measurement noises. Finally, the simulations are conducted to verify the effectiveness of the proposed controller. The theoretical analysis and simulation results demonstrated that the NREDO can not only effectively suppress the effect of measurement noise, but also inherit the advantages of the EDO in avoiding redundant estimation of the system states and dealing with the nonlinear item of the spacecraft model. Improved attitude control performance can be achieved under the proposed NREDO-based controller.

Atrial fibrillation (AF) is a common clinical arrhythmia with a lifetime risk and has become an attractive topic of clinical research and health management. Although the 12-lead classical ECG configuration is adequate for the detection of AF, its configuration is suboptimal for constructing surface potential mapping or extracting other diagnostic features during AF. Body surface potential mapping (BSPM) has a broad application prospect in AF study, but the electrode wiring is complicated and the hardware cost is high. This paper proposes a method to improve the performance of leads selection algorithm from a 128-lead BSPM system with equidistantly spaced electrodes. 128-lead BSPM data obtained from 8 AF patients were used in the study. Leads selection was performed by a sequential selection based on an adapted Botteron's approach and multiple linear regression. The result showed that the proposed method has significant improvement on the performance of the accurate reconstruction of dominant frequency on the patient-specific dataset. The proposed method may not only improve the performance on the spectrum characteristic but also effectively improve the performance of time domain criteria when the number of selected leads is above 12.

Summary: Background: Billroth Ⅰ (BⅠ) reconstruction and Roux-en-Y (RY) reconstruction are both commonly performed after distal gastrectomy (DG). We conducted a retrospective study to evaluate which is the better option. Methods: Included in our study were 162 patients who, between April 2011 and October 2015, underwent DG followed by BⅠ reconstruction (n = 93) or RY reconstruction (n = 69). All patients were followed up for at least 1 year. We compared perioperative outcomes, postoperative complications, gastrointestinal (GI) symptoms, endoscopic findings, and nutritional status between the 2 groups of patients. Results: Patient characteristics did not differ between the 2 groups, with the exception of the incidence of gastric body tumors, which was significantly higher in the RY group (73.9% vs. 19.4%; p

The aim of this study was to obtain accurate angular positions and velocities from resolver signals; resolver-to-digital conversion (RDC) often adopts a phase-locked loop (PLL) as a demodulation algorithm. However, resolver signals often come with quadrature errors and harmonics, which lead to a severe reduction in PLL accuracy. The conventional PLL does not consider the impact of the quadrature error, and the bandwidth of the PLL is much larger than the fundamental frequency of resolver signals for pursuing a low dynamic error. These reasons render the retention of resolver harmonics in the demodulation results. In this paper, a disturbance-compensated PLL (DC-PLL) is proposed, which consists of a phase detector for suppressing quadrature error and harmonics (SQEH-PD) and a second-order observer. Firstly, since the quadrature error does not change with the angle velocity, the pre-estimated quadrature error is used in the SQEH-PD to compensate for the quadrature error in resolver signals. Secondly, although the frequency of the harmonics changes with the velocity, the amplitudes of the harmonics do not change. Therefore, the pre-estimated amplitudes of harmonics and estimated angular position are used in the SQEH-PD to compensate for the harmonics in resolver signals. Thirdly, a second-order observer is designed to estimate the angular position and velocity by regulating the phase detector error. Compared with the conventional PLL, the proposed DC-PLL has a stronger anti-disturbance ability against the quadrature error and harmonics by configurating the phase detector error and the estimated position error, which have a linear relation. Simulation and experimental results prove the effectiveness of the proposed method.

Inhomogeneous structures with carbon nanotubes (CNTs), reinforced with Cu composite foams as the reinforcing skeletons (CNTs/Cuf®Cu), have been designed to overcome the paradox between strength and ductility or conductivity in copper matrix composites. The interface between CNTs and the copper matrix is usually weak, due to poor wettability and interaction. In this study, nickel nanoparticles are decorated onto CNTs to improve interfacial bonding. The broader interface transition area between CNTs and copper with Ni3C interfacial products formed, and a combination of improved electrical conductivity (95.6% IACS), tensile strength (364.9 MPa), and elongation (40.6%) was achieved for the Ni-decorated CNTs/Cuf®Cu (Ni-CNTs/Cuf®Cu). In addition, the strengthening mechanisms are discussed in this study.

Hierarchically ordered porous silica materials (HSMs) with a micro/mesoporous structure were successfully prepared with the sol-gel method using dextran, dextran/CTAB, and CTAB as templates. The obtained hierarchically structured silica was successfully modified with amine groups through post-grafting and one-pot methods. Their architectural features and texture parameters were characterized by XRD, N2 adsorption–desorption isotherms, SEM, TEM, FTIR, and TGA techniques. The results demonstrated that the pore structure depended on the reaction temperature and the amount of CTAB added in the synthesis procedure. A series of porous silica with hierarchical pore structures possessed abundant micropores, ordered mesopores, and a tunable surface area and pore volume. After modification, the ordered structure of the hierarchical porous silica almost disappeared due to the presence of amine groups in the pore channel. Furthermore, to explore the effect of pore structures and amine groups on CO2 adsorption performance, before and after amine modification of HSMs, adsorbents were evaluated regarding the capacity of collecting CO2 for comparison. According to these results, the varying microporous content, pore size distribution, and density of the amine groups were important factors determining the capacity of CO2 capture.

Thyroid cancer is the most common type of endocrine malignancy. Although the general prognosis is good, the treatment of advanced disease is still challenging. Exosomes are vesicle units containing specific components that transmit information between cells. In order to explore its role in papillary thyroid cancer (PTC), our study screened exosome enriched lncRNA SNHG9 by lncRNA chip and explored its biological function. We used lncRNA chips combined with bioinformatics analysis to screen lncRNA SNHG9 enriched in exosomes. GO analysis suggested its relationship with autophagy and apoptosis. Quantitative PCR showed SNHG9 was highly expressed in PTC cells and exosomes and its correlation with PTC tumor size was analyzed by clinical characteristics. SNHG9 could inhibit the protective cell autophagy induced by starvation of human normal thyroid epithelial cell line Nthy-ori-3 and promote its apoptosis through PTC cell exosomes. RNA-pull down combined with protein spectrum showed that SNHG9 could interact with YBOX3. Western blot and RNA immunoprecipitation further confirmed their interaction. Western blot showed that SNHG9 could induce degradation of YBOX3, thus interfering with the stability of P21 mRNA and inducing cell apoptosis. In conclusion, our study identified SNHG9 as a PTC cell exosome-enriched lncRNA. SNHG9 could inhibit cell autophagy and promote apoptosis of Nthy-ori-3 cell through YBOX3/P21 pathway.

Right heart thrombus accompanied by chronic thromboembolic pulmonary hypertension is a rare entity. Right heart thrombus may develop in the peripheral veins or in situ within the right heart chambers. The diagnosis of right heart thrombus is challenging, since its symptoms are typically non-specific and its imaging features resemble those of cardiac masses. Here, we report two cases of right heart thrombus with chronic thromboembolic pulmonary hypertension that presented as right ventricular masses initially. Both patients underwent simultaneous pulmonary endarterectomy and resection of the ventricular thrombi. Thus, when mass-like features are confirmed by imaging, right heart thrombus should be suspected in patients with chronic thromboembolic pulmonary hypertension, and simultaneous right heart thrombus resection is required along with pulmonary endarterectomy.

NiMn layered double hydroxide (Ni3Mn-LDH) has been found to be an efficient catalyst for the oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) using molecular oxygen as the sole oxidant. Various reaction conditions on the oxidation have been investigated, and impressive catalytic performance, good stability and recyclability have been observed for Ni3Mn-LDH. Both of Ni2+ and Mn3+ species in the structure were proposed to be the catalytically active site for the aerobic oxidation of HMF, and the two species in the transformation exhibited synergistic effect.

The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (DRP1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking Dnm1l in adult AgRP neurons (Drp1 cKO) show decreased fasting- or ghrelin-induced AgRP neuronal activity and feeding and exhibited a significant decrease in body weight, fat mass, and feeding accompanied by a significant increase in energy expenditure. In support of the role for mitochondrial fission and fatty acids oxidation, Drp1 cKO mice showed attenuated palmitic acid-induced mitochondrial respiration. Altogether, our data revealed that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons is a critical mechanism for AgRP neuronal function and body-weight regulation.

The metal tolerance mechanism of plants is of great importance to explore the plant-based clean-up of environmental substrata contaminated by heavy metals. Indoor experiment of tobacco (Nicotiana tabacum L.) seedlings growing hydroponically in nutrient solution containing 0, 0.1, 0.5, 2.0, and 4.0 mg L−1 V was conducted. The results indicated that plant overall growth performance was significantly affected at ≥ 2.0 mg L−1 V. Oxidative stress degree as indicated by foliar O2−· and H2O2 content intensified markedly at ≥ 0.5 mg L−1 V treatments. In response, the plant activated its enzyme and non-enzyme protecting mechanism to cope with oxidative stress inflicted by vanadium. The activities of antioxidant enzymes, including SOD, POD, CAT, APX, and the concentration of non-enzyme antioxidants, e.g., AsA and GSH were all conspicuously (p

The interruption of supply chain caused by unexpected events results in great economic losses. In this paper, we consider that the supply chain risk management consists of a manufacturer and a retailer faced with demand and supply uncertainties caused by the interruption of supply chain. We consider that the manufacturer transfers the disruption risk by purchasing BI (business interruption) insurance. Three models are established to illustrate the impact of insurance on supply chain decision-making under risk. It is observed that business interruption insurance can increase the retailer’s order quantity and supply chain profit. The higher the interrupt probability is, the more obvious the value of the business interruption insurance is. Furthermore, the retailer helps the manufacturer to share the premium, and the manufacture shares the proceeds of insurance with the retailer, which can stimulate retailer to order more and increase the profit of manufacturer and retailer.

Sustainable development is an everlasting theme and lasting strategy in today’s era. Low-carbon economy is an inevitable approach to the implementation of sustainable development. Cold chain logistics has become one of the main sources of carbon emissions. However, in the research on location planning of cold chain logistics, the costs of carbon emissions have not been taken into consideration in previous studies. The two-stage stochastic optimization (TSSO) model was established based on the comprehensive consideration of transportation costs, time penalty costs, and carbon emission costs. In this case, it is extremely difficult to deal with uncertainty in TSSO model. Therefore, this paper constructs a two-stage robust optimization (TSRO) model using data-driven method and robust optimization theory and verifies the validity of this model through an actual case. The application of this method to a cold chain logistics enterprise showed that the service level of logistics cannot be guaranteed by stochastic optimization model. In the TSRO model, the costs increase by 2.18% at the price of robustness, whereas logistics service level shows an upward trend (from 85.83% to 92.75%). In the TSRO model, enterprises are forced to choose a better distribution path when carbon tax increases, which not only helps enterprises save costs but also achieves low-carbon environmental benefits.

It is of great significance to study the spatial network of the new energy vehicle (NEV) industry innovation efficiency and its factors to promote the rational allocation of innovative resources and the coordinated development of Chinese NEV industry. First, the Super Efficiency Data Envelope Analysis model is used to measure innovation efficiency in the NEV industry in Chinese provinces, and based on the results, the improved gravity model is applied to construct a spatial correlation network. Then, by applying social network analysis (SNA) to study NEV industry development node spatial correlations, we conclude that there is no overall hierarchical structure. The SNA are applied to examine spatial correlations with respect to NEV industry innovation efficiency in each province, and to analyze the role and position of each province in the spatial correlation network. Finally, the influencing factors of spatial correlation of the innovation efficiency of China's NEV industry has been discussed. The result shows that the difference in spatial distance and R&D investment has a significant impact on the spatial correlation of the NEV industry.

Investment portfolio can provide investors with a more robust financial management plan, but the uncertainty of its parameters is a key factor affecting performance. This paper conducts research on investment portfolios and constructs a two-stage mixed integer programming (TS-MIP) model, which comprehensively considers the five dimensions of profit, diversity, skewness, information entropy, and conditional value at risk. But the deterministic TS-MIP model cannot cope with the uncertainty. Therefore, this paper constructs a two-stage robust optimization (TS-RO) model by introducing robust optimization theory. In case experiments, data crawler technology is used to obtain actual data from real websites, and a variety of methods are used to verify the effectiveness of the proposed model in dealing with uncertainty. The comparison of models found that, compared with the traditional equal weight model, the investment benefits of the TS-MIP model and the TS-RO model proposed have been improved. Among them, the Sharpe ratio, Sortino ratio, and Treynor ratio have the largest increase of 19.30%, 8.25%, and 7.34%, respectively.

Insomnia, one of the most common sleep disorders, is thought to have an adverse effect on cognitive function. At the same time, people with cognitive dysfunction are more prone to insomnia. At present, pharmacotherapy is the main treatment for insomnia, but there are some shortcomings such as poor long-term efficacy and potential dependence. There is some evidence that acupuncture has some advantages in alleviating insomnia and improving cognitive function. This study is aimed at investigating the effects of acupuncture and drugs on cognitive function in patients with insomnia and evaluating the efficacy and safety of these two interventions, providing strong evidence for clinical decision-making. The study will retrieve eight major databases: China National Knowledge Infrastructure, Wanfang Database, VIP Database for Chinese Technical Periodicals, SinoMed, PubMed, Web of Science, Embase, and Cochrane Library. Dissertations, conference papers, and ongoing experiments will also be retrieved for supplement. Literature screening and data extraction will be completed by two authors independently (JJ and X-QW). If there were any disagreements, they would be discussed or referred to a third person for adjudication (W-ZW). Authors will use Cochrane risk of bias tool to assess the included studies. The Review Manager Statistical (RevMan) software is used to conduct the statistical process of meta-analysis, and funnel plot is used to evaluate reporting biases. The Grading of Recommendations Assessment Development and Evaluation (GRADE) Profiler can be used to be aware of the quality of evidence.

Logistics distribution plays an important role in the operation of e-commerce firms. This paper considers two logistics distribution modes with service competition: the e-commerce platform self-distribution (SDL) mode and third-party logistics (TPL) mode. By introducing consumer behavior into the model, we examine the competition between two firms with the same functionalities in the context of e-commerce. According to the real scene, we build the corresponding mathematical optimization model. Each firm needs to decide a logistics distribution mode and a corresponding price for the selected logistics mode. We first analyze the two firms chosen logistics modes and prices simultaneously and then extend it to Stackelberg game situation. We find out the optimal strategy for two firms. Finally, we propose numerical analysis to identify our models and provide a series of managerial insights.

Demagnetization in permanent magnet synchronous motor (PMSM), caused by high temperature or inverse magnetic field, may increase loss and torque ripple, and even degrade the system stability in severe cases. On-line detection can identify the incipient demagnetization of permanent magnets (PMs), as well as providing reference for subsequent fault-tolerant control, so as to avoid further demagnetization. Therefore, an on-line demagnetization detection method is proposed in this paper by using flux observer. First, an observer is established in the three-phase stationary reference frame by taking the stator currents and the amplitudes of the fundamental and harmonic components of flux as state variables. Then, three demagnetization indexes are presented to evaluate the properties of PMs based on the observed flux information. The proposed method can directly track the amplitude of harmonic flux and evaluate the severity of the demagnetization more comprehensively. Simulation and experimental results demonstrate the effectiveness of the proposed method.

The application of NaCl-based aluminum-air batteries is limited due to the passivation of the aluminum anode. In an effort to solve this problem, this work studied the influence of different concentrations of Ga3+ additives on the discharge behavior of Al in the NaCl electrolyte. The results of both experiments and theoretical calculations have shown that commercial purity aluminum could be significantly activated by Ga3+. Based on microstructure observations and electrochemical impedance spectroscopy, the influence activation mechanism of Ga3+ on the discharge behavior of commercial purity Al is clarified. The addition of Ga3+ biased the surface charge of aluminum along the activation direction, forming activation sites, and then destroyed the surface passivation film. Due to the formation of a gallium–aluminum amalgam, the Al-air battery had the best discharge characteristics in the electrolyte with 0.2 M Ga3+, and its discharge voltage reached 0.9734 V with a remarkable increase compared with that of NaCl solution (0.4228 V). Therefore, Ga3+ additive is a promising choice for NaCl-based Al-air batteries to improve their discharge voltage.

Background Clinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.Methods We isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.Results We documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.Conclusions Our results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.

This study focused on the expression of mitochondrial serine hydroxymethyltransferase (SHMT2) in oral squamous cell carcinoma (OSCC) and its correlation with clinical traits and the prognosis of OSCC patients. Immunochemical staining and Western blotting were used to quantify the expression of SHMT2 and related immune markers in OSCC. Using OSCC microarrays and The Cancer Genome Atlas (TCGA) database, we evaluated the association between SHMT2 and various clinical traits. We found that increased expression of SHMT2 was detected in OSCC and correlated with advanced pathological grade and recurrence of OSCC. By a multivariate Cox proportional hazard model, high expression of SHMT2 was shown to indicate a negative prognosis. In addition, in the OSCC microenvironment, increasing the expression of SHMT2 was associated with high expression levels of programmed cell death-ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain containing 6 (CMTM6), V-type immunoglobulin domain-containing suppressor (VISTA), B7-H4, Slug, and CD317. In the future, more effort will be required to investigate the role of SHMT2 in the OSCC microenvironment.

A bioactive acidic tea polysaccharide from yellow leaves of Wuyi rock tea was successively prepared via DEAE-52 and Superdex-200 columns. Nuclear magnetic resonance (NMR) analysis showed that the main glycosidic bonds were composed of α-l-Araf-(1→, →5)-α-l-Araf-(1→, →4)-α-d-Glcp-(1→, Arap-(1→, →6)-α-d-Glcp-(1→, →2,4)-α-l-Rhap-(1→, →3,4)-α-d-Glcp-(1→, →4)-α-d-GalAp-(1→, →4)-α-d-GalAp-(1→, α-d-Galp-(1→, →6)-β-d-Galp-(1→ and →4)-β-d-Galp-(1→. The molecular weight was 3.9285 × 104 Da. The hypoglycemic effect of acidic tea polysaccharides on streptozotocin-induced type 2 diabetes mellitus rats was evaluated through histopathology and biochemistry analysis. The acidic tea polysaccharide could improve plasma and liver lipid metabolism. Moreover, 16S rRNA gene sequencing revealed that the composition of the intestinal flora changed drastically after treatment, namely, blooms of Bifidobacterium, Blautia, Dorea, and Oscillospira, and a strong reduction in Desulfovibrio and Lactobacillus. The above results illustrated that tea polysaccharides might serve as an effective ingredient to ameliorate glucose metabolism disorders and intestinal flora in hyperglycemic rats.

Abstract Background Accumulation of evidence indicates that miRNAs have crucial roles in the regulation of EMT-associated properties, such as proliferation, migration and invasion. However, the underlying molecular mechanisms are not entirely illustrated. Here, we investigated the role of miR-296-5p in hepatocellular carcinoma (HCC) progression. Methods In vitro cell morphology, proliferation, migration and invasion were compared between HCC cell lines with up- or down-regulation of miR-296-5p. Immunofluorescence and Western blot immunofluorescence assays were used to detect the expression of EMT markers. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-296-5p. Xenograft nude mouse models were established to observe tumor growth and metastasis. Immunohistochemical assays were conducted to study the relationships between miR-296-5p expression and Neuregulin-1 (NRG1)/EMT markers in human HCC samples and mice. Results miR-296-5p was prominently downregulated in HCC tissues relative to adjacent normal liver tissues and associated with favorable prognosis. Overexpression of miR-296-5p inhibited EMT along with migration and invasion of HCC cells via suppressing NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling in vitro. More importantly, miR-296-5p disrupted intrahepatic and pulmonary metastasis in vivo. NRG1, as a direct target of miR-296-5p, mediates downstream biological responses. In HCC tissues from patients and mice, the levels of miR-296-5p and NRG1 also showed an inverse relationship. Conclusions miR-296-5p inhibited EMT-related metastasis of HCC through NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling.

NaoShuanTong capsule (NSTC) has been commonly used to treat blood circulation disorders and neurological dysfunction against cerebral ischemia in China. In this study, using an acute blood stasis rat model, canonical correlation analysis between chemical high performance liquid chromatography (HPLC) fingerprint and in vivo biotests was conducted to discover and identify the bioactive compounds responsible for NSTC’s protective effects on hemorheological disorders. Four independent effect components were extracted from the 12 originally detected parameters. Three bioactive compounds were found to have significant contribution in two or more effect components against hemorheological disorders. Typhaneoside could influence the erythrocyte aggregation and coagulation function. Isorhamnetin-3-O-neohesperidoside had impacts on the erythrocyte aggregation, erythrocyte deformability and platelet aggregation. Benzoyl-oxypaeoniflorin was associated with erythrocyte aggregation, coagulation function and platelet aggregation. The findings could offer useful references for NSTC’s quality control and clinical practice. Abbreviations Adradrenaline ASPaspirin APTTactivated partial thromboplastin time CCAcanonical correlation analysis EAIerythrocyte aggregation index EDIerythrocyte deformability index EEIerythrocyte electrophoresis index HCThaematokrit HPLChigh performance liquid chromatography MPARmaximum platelet aggregation rate NSTCNaoShuanTong Capsule PCAprincipal component analysis PTPollen Typhae PTprothrombin time PVplasma viscosity RCRadix Curcumae RGRhizome Gastrodiae RPRRadix Paeoniae Rubra RRRadix Rhapontici TCMtraditional Chinese medicine WBVwhole blood viscosit

Background/Aims: microRNAs are of vital importance in neural development. As a brain-specific miRNA, miR-132 has been well studied in mature neurons. However, its role in neural stem cells (NSCs) remains unclear. In this study, we investigated the role of miR-132 in regulating NSCs proliferation, differentiation and neuronal maturation. Methods: NSCs were obtained from fetal mice spinal cord. Proliferation, cell cycle, cell apoptosis, cell motility were measured through CCK-8, BrdU, AnnexinV-FITC/PI and migration assay respectively. The expression of synaptic proteins and ERK1/2 pathway were detected by western blot. The inactivation of Notch pathway was checked using qPCR. The neurite outgrowth was recorded using Image J software and Neuron J software. Dendritic length was further analyzed through sholl analysis. Fate determination of NSCs, developmental synapse formation was assessed by immunostaining. Results: miR-132 negatively regulated NSCs proliferation by affecting the cell cycle and promoting apoptosis. Inactivated Notch-Hes1pathway was observed in miR-132 overexpression cells. miR-132 was significantly increased in differentiating NSCs following activation of ERK1/2 pathway. miR-132 could impair neuronal differentiation but promote glial cell differentiation by regulating Mecp2 expression. miR-132 was implicated in neurite outgrowth but slightly inhibited postsynaptic PSD-95 expression. The differentiated neurons exhibited normal electrophysiological characteristics, and already interacted with other neurons to form synaptic-like structures. Conclusion: miR-132 was demonstrated as a negative regulator for NSCs self-renewal, neuronal differentiation but promoted glial cell differentiation and neurite outgrowth.

In control moment gyroscopes (CMGs), the gimbal is expected to rotate at a low speed with high precision so that high-precision gyroscopic torque can be generated to realize high-precision spacecraft attitude control. However, there are complex and multiple disturbances in the gimbal servo systems, which may deteriorate the gimbal control performance to a great extent. In this paper, an extended harmonic disturbance observer (EHDO)-based composite controller is proposed to reject the effects of multiple disturbances on the control performance of gimbal servo systems. Firstly, an EHDO is developed for an mth-order model describing disturbance dynamics in which the rotor dynamic imbalance torque along gimbal axis is modeled as a harmonic, and the others are approximated as a polynomial. Compared with conventional extended disturbance observers, EHDO can estimate multiple disturbances with high precision even with a lower bandwidth. Secondly, a backstepping-based composite controller is designed to achieve high-performance gimbal control for CMGs. Finally, simulation and experimental results are presented to demonstrate the effectiveness of the proposed method.

Wind disturbance may significantly degrade the attitude control performance during the flight of quadrotor vehicles. In order to meet the requirement of high-precision attitude control, a generalized extend state observer (GESO)-based disturbance and uncertainty estimation and attenuation control strategy is proposed in this paper. First, the disturbances are considered as a time polynomial function, and the nth order model of disturbances are augmented into the quadrotor dynamics. According to the reconstructed model, a GESO is designed and its stability is proved by the Lyapunov theory. Then, we analyze the influences of the observer order and bandwidth on the estimation accuracy in detail and give the gain tuning guidelines for GESO. Second, we design an attitude tracking controller based on the backstepping method and discuss the stability of the entire system. Finally, the numerical simulations and real-time experiments are carried out to evaluate the performance of the proposed controller with the GESO of different orders. Our results show that the proposed method can achieve precise attitude tracking for a quadrotor subject to wind disturbance. Furthermore, when the bandwidth of the GESO is fixed, the performance of the proposed controller improves with the increases of the GESO order.

Background/Aims: Serine/threonine kinase 35 (STK35) may be associated with Parkinson disease and human colorectal cancer, but there have been no reports on the expression levels or roles of STK35 in osteosarcoma. Methods: STK35 mRNA expression was determined in osteosarcoma and bone cyst tissues by real-time PCR. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. Results: STK35 was up-regulated in osteosarcoma tissues as indicated by analyzing publicly available expression data (GEO dataset E-MEXP-3628) and real-time PCR analysis on our own cohort. We subsequently investigated the effects of STK35 knockdown on two osteosarcoma cell lines, MG63 and U2OS. STK35 knockdown inhibited the growth of osteosarcoma cells in vitro and in xenograft tumors. Meanwhile, STK35 knockdown enhanced apoptosis. Expression of the active forms and the activity of two major executioner caspases, caspase 3 and caspase 7, were also increased in osteosarcoma cells with STK35 silenced. Additionally, Gene Set Enrichment Analysis (GSEA) identified that the JAK/STAT signaling pathway was positively correlated with STK35 expression. The mRNA expression of STK35 was repressed by STAT3 small interfering RNA (siRNA), but not by siRNA of STAT4, STAT5A or STAT6. A luciferase reporter assay further demonstrated that STAT3 transcriptionally regulated STK35 expression. A chromatin immunoprecipitation (ChIP) assay confirmed the direct recruitment of STAT3 to the STK35 promoter. The promotion effects of STAT3 knockdown on cell apoptosis were partially abolished by STK35 overexpression. Furthermore, STK35 mRNA expression was positively correlated with STAT3 mRNA expression in osteosarcoma tissues by Pearson correlation analysis. Conclusions: These results collectively reveal that STAT3 regulates the transcription of STK35 in osteosarcoma. STK35 may exert an oncogenic role in osteosarcoma.