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Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-β network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF-1α network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF-1α and its three targets SNAIL, TWIST, and miR-210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT.

Liver fibrosis (LF) is the result of a vicious cycle between inflammation‐induced chronic hepatocyte injury and persistent activation of hepatic stellate cells (HSCs). Mesenchymal stem cell (MSC)‐based therapy may represent a potential remedy for treatment of LF. However, the fate of transplanted MSCs in LF remains largely unknown. In the present study, the fate and antifibrotic effect of MSCs were explored in a LF model induced by CCl4 in mouse. Additionally, MSCs were stimulated in vitro with LF‐associated factors, tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), and transforming growth factor‐β1 (TGF‐β1), to mimic the LF microenvironment. We unveiled that MSCs exhibited autophagy in response to the LF microenvironment through Becn1 upregulation both in vivo and in vitro. However, autophagy suppression induced by Becn1 knockdown in MSCs resulted in enhanced antifibrotic effects on LF. The improved antifibrotic potential of MSCs may be attributable to their inhibitory effects on T lymphocyte infiltration, HSCs proliferation, as well as production of TNF‐α, IFN‐γ, and TGF‐β1, which may be partially mediated by elevated paracrine secretion of PTGS2/PGE2. Thus, autophagy manipulation in MSCs may be a novel strategy to promote their antifibrotic efficacy., We found that mesenchymal stem cells (MSCs) underwent autophagy in response to liver fibrosis (LF) microenvironment by upregulating BECN1 expression. Inhibition of autophagy induced by Becn1 knockdown in MSCs promoted their antifibrotic efficacy on CCl4‐induced LF. The improved antifibrotic potential of MSCs might be attributed to their inhibitory effects on T lymphocyte infiltration, hepatic stellate cell proliferation, as well as production of TNF‐α, IFN‐γ, and TGF‐β1, which might be partially mediated by elevated paracrine secretion of PTGS2/PGE2.

Two new ingol-type diterpenes, euphoresins A-B (

Periostracum Cicadae, the cast-off shell of the cicada Cryptotympana pustulata Fabricius, is used in traditional Chinese medicine for its diaphoretic, anticonvulsive, sedative, antipyretic, and antiallergic effects. Five new N - acetyldopamine dimers were isolated from Periostracum Cicadae, and their structures were elucidated as (2 R ,3 S )-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-7-( N- acetyl-2′′-aminoethyl)-1,4-benzodioxane 3′- O -β- d -glucopyranoside ( 1 ), (2 S ,3 R )-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-7-( N -acetyl-2′′-amino-1′′-hydroxylethyl)-1,4-benzodioxane ( 2 ), (2 R ,3 S )-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-6-( N -acetyl-2′′-amino-1′′-hydroxylethyl)-1,4-benzodioxane ( 3 ), (2 S, 3 S )-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-6-( N -acetyl-2′′-aminoethyl)-1,4-benzodioxane (4) , and (2 S ,3 S )-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-7-( N -acetyl-2′′-aminoethylene)-1,4-benzodioxane (5) by analysis of one-dimensional NMR, two-dimensional NMR, mass spectrometry, CD spectroscopy, and chemical evidence. We showed that treatment with 2 , 4 , or 5 at a concentration of 400 μM significantly inhibited LPS-induced increases in NO content in RAW264.7 cells. Our results suggest that newly isolated compounds 2 , 4 , and 5 might mediate the biological effects of Periostracum Cicadae, and future in vivo studies will determine their therapeutic potential.

Based on the quasi-boson approach, a model of a Λ-type three-level atom coupled to a X-shaped coupled cavity arrays (CCAs) is used to study the transport properties of a single-photon in the dissipative case, and a classical field is introduced to motivate the one transition of the Λ-type three-level atom (ΛTLA). The analytical expressions of transmission and transfer rate are obtained. Our results show that the cavity dissipation will obviously weaken the single-photon transfer rate where the incident energy of the single photon is resonant with the excited energy of the atom. Whether the cavity dissipation exists or not, the single photon can be almost confined in the incident channel at large detuning, and we can regulate the intensity of the classical field to control the total transmission of the single-photon.

Ten triterpenes compounds were isolated from the methanol extraction of the latex of Euphorbia resinifera by means of various chromatographic methods such as silica gel, ODS and semi-preparative HPLC, Their structures were identified by spectroscopic methods and physicochemical properties. These isolated compounds were identified as 3

The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4‑induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4‑induced liver fibrosis; group 3, CCl4+Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P

Five new N-acetyldopamine (NADA) derivatives (1–5) and one known NADA quinone methide (6) were isolated from Periostracum Cicadae (the cast-off shell of the cicada Cryptotympana pustulata Fabricius), which is known as chantui in China and is used in traditional Chinese medicine to treat soreness of the throat, hoarseness, itching, and spasms. By combined analysis of one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, CD spectra, and chemical evidence, the structures of the isolated compounds were established as (R)-N-(2-(3,4-dihydroxyphenyl)-1-ethoxy-2-oxoethyl)acetamide (1), (1R,2R)-N-(1,2-diethoxy-2-(3,4-dihydroxyphenyl)-ethyl)acetamide (2), (R)-N-(1-acetamido-2-ethoxy-2-(3,4-dihydroxyphenyl)-ethyl)acetamide (3), (1R,2R)-N-(2-(3,4-dihydroxyphenyl)-2-ethoxy-1-methoxyethyl)acetamide (4), (1S,2S)-N-(2-(3,4-dihydroxyphenyl)-2-ethoxy-1-methoxyethyl)acetamide (5), and (R)-N-(2-(3,4-dihydroxyphenyl)-2-methoxyethyl)acetamide (6).

Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin ( α-SMA), TGF-β1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-β1 were measured by real-time PCR. Collagen I and transforming growth factor β1 (TGF-β1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups ( P 4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

Traditional platform-centric command mode has been unable to meet the needs of modern war. In this paper, a new command mode for ship formation cooperative engagement based on networked condition has been discussed. First, the characteristics of ship formation cooperative engagement are elaborated. Then, the command relationships of ship formation are researched. On the basis, a self-adaptive command mode is proposed to adapt ship formation cooperative engagement under the network condition. Command authority distribution and self-synchronization of this command mode are described, which is important to enhance the adaptability and timeliness of combat command of ship formation cooperative engagement.

In order to better adapt to the change from platform-centric warfare to network-centric warfare, the cooperation and key technologies in command and control are researched. Firstly the concept and connotation on cooperation and cooperative engagement are described. Then, the hierarchy, content and pattern of cooperation in command and control of maritime formation combat under informationization are expounded. Finally the crucial technologies supporting for cooperation in command and control are pointed out. This research provides new ideas and methods for command and control technologies of maritime integrated cooperative engagement.

Multiple Rounds Simultaneous Impact shooting method (MRSI) improved the hit projectiles greatly.It will effect the shooting effectiveness of Large Caliber Naval Gun weapon system.Based on the analysis of the priciple of Monte Carlo method,the consistent of shooting errors was given.Then built the configuration rules of aiming points,and given the Optimal configuration.Also the Monte Carlo method was adopt to calculate the shooting effectiveness of Large Caliber Naval Gun weapon system.The simulation results showes that MRSI shooting method could attack the moving targets effectively.

Path planning has always being one of the most significant study fields in Small UAV researching. And Model Predictive Control (MPC) is a special strategy in obtaining the control actions which were achieved by solving a finite horizon optimal control problem at each instant. The paper advanced a novel method which was called Model Predictive Path Planning Strategy (MPPS) based on MPC to deal with the SUAV path planning problem and a responding predictive planner was put forward to generate an effective path for SUAV in simulative urban environment. The results of the simulation show that the advanced method can be used to plan path for SUAV.

In order to eliminate the influence of sensor system errors on detecting precision, the intersection of sensor locating globes is modeled with Earth-Center Earth-Fixed coordinates as transitional characters and to be eliminated, and a self-adaptive filter is presented to register sensor system errors for multi-platform, which identifies model characters and error characters on line by innovation correlation function sequence based on real-time mutual observation of platforms. Contrastive simulations against traditional registration algorithm show that the registration algorithm based on innovation correlation can converge quickly with high precision.

Aiming at time and sensor system errors which are influential on detecting precision of sensors, the transfer relation of time and sensor system errors is modeled and a least square estimation algorithm is presented, based on navigation data with high precision and real-time observation of an aerial platform. Contrast among true value, observation and registered value by simulations show that the registration algorithm of time and sensor system errors for multi-platform can converge quickly with high precision.

Based on Crammer-Rao Lower Bound (CRLB), this paper adopts Geometric Dilution of Precision (GDOP) as the optimizing performance index to analyze the localization precision in Bearing-only localization for single observer. And the genetic algorithm is employed to calculate the optimal course sequence. The movement straight with constant velocity and movement with constant prefix angles are analyzed. Simulations show that maneuvering trajectory is propitious to improve localization precision.

To establish the uniform situation map, the platforms’ low-precision navigation information and the location information measured mutually are used to carry out the sensor data alignment for martime multi-platforms. This method can avoid the dependences on high-precision navigation equipments and the errors introduced by assuming the earth’s surface to be the plane. The models of coordinate conversion for aligning are presented. Then the measure equations and the state equations with regard to navigation systematic error and sensor systematic error are built respectively, and a registration algorithm based on Unscented Kalman filtering is designed for estimating online and compensating those two systematic errors. Consequently, the error registration for martime multi-platforms is achieved, and the higher precision information can be provided for the subsequent data association and data fusion. The simulation results demonstrate the correctness and validity of the algorithm.

Autophagy is an evolutionarily conserved lysosomal mechanism implicated in a wide variety of pathological processes, such as cancer. Autophagy can be regulated by a limited number of autophagy‐related genes (Atgs) such as oncogenic Bcl‐2/Bcl‐X (L), mTORC1, Akt and PI3KCI, and tumour suppressive proteins PI3KCIII, Beclin‐1, Bif‐1, p53, DAPKs, PTEN and UVRAG, which play their crucial roles in regulating autophagy‐related cancer. As autophagy has a dual role in cancer cells, with tumour‐promoting and tumour‐suppressing properties, it has become an attractive target for a series of emerging small molecule drugs. In this review, we reveal new discoveries of related small molecules or chemical compounds that can regulate autophagic pathways and lead to pro‐death or pro‐survival autophagy, in different types of cancer. We discuss the knots between autophagic targets and candidate drugs, in the hope of shedding new light on exploiting new anti‐tumour small molecule drugs for future cancer therapy.

In order to eliminate the influences of time wrap and sensor system errors on precision of multi-sensor data fusion in maritime cooperation of multi-platform, the transfer relation between Earth-Center Earth-Fixed coordinate system and Cartesian coordinate frame described by navigation information is modeled, in which Earth-Center Earth-Fixed coordinates are transitional characters and to be eliminated. Combined with innovation correlation function sequence, a self-adaptive filter is presented to register time and sensor system errors for multi-platform, which identifies model characters and error characters on line. Contrastive simulations show that the registration algorithm based on high-precision navigation equipments can converge quickly with high precision.

The handoff model of missile trajectory from midcourse guidance to terminal guidance is studied for antiaircraft missile using radar updated inertial midcourse guidance combined with active radar homing terminal guidance. Based on the interspersing rule of missile and target, the probability of successful handoff of missile trajectory is calculated by introducing the guiding rule to handoff model. Factors influencing the probability of successful handoff of missile trajectory are analyzed by simulation and appropriate trajectory parameters for guiding and controlling missile can be calculated.

The energy consumption problem is always a critical issue in the research of WSNs. The sleep mechanism, an effective energy-saving technique, is widely studied and employed. The Energy Map describing the information of the remaining energy in each part of the network is useful to prolong the lifetime of the network. In this paper, a GSPN-based model to predict the energy consumption of a WSN with the sleep mechanism is proposed for constructing the energy map, and the model provides the theoretical basis and numerical foundation for making efficient use of energy.

To solve data alignment problem of multi-platform multi-sensor on the sea, a multi-sensor data alignment method based on relative bearing and range is proposed. Using the measurements of relative bearing and range among the maritime platforms, the targets' positions measured are transformed in the sensor relative bearing cordinates of a platform, and the sensor alignment is achieved. The method above can be implemented by means of two coordinate transformation approachs. The alignment mechanisms and mathematical models of both approachs are discussed. Through several simulation scenarios, the precision of two transformation approachs are analysed and campared. Simulation results are employed to decide two approachs' applicable environment according to the precision requirements of establishing the fire-control-level situation.

An anytime algorithm based on modified genetic algorithm (GA) for dynamic WTA problem, subject to temporal constraints, is developed in the paper. In the algorithm the weapons are assigned to targets one by one before the deadline of each target comes. After a target is assigned with some weapon, the target is replaced by a new one in all chromosomes in the population while the optimization process will not undergo any restart. The algorithm has three main advantages: 1) a new target can be dynamically accommodated in the allocation process without losing previous optimizing information, 2) the quality of the pairing decisions may be improved in the evolving process with a prolonged computation time, and 3) it optimally deploys weapons to targets where a weapon can be assigned to more than one target asynchronously without missing any deadline of the targets, under the precondition that the weapon can be allocated to only one target at one time. The feasibility and the validity of the modified GA are verified in simulations.