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The exploration of Mars would heavily rely on Martian rocks mechanics and engineering technology. As the mechanical property of Martian rocks is uncertain, it is of utmost importance to predict the probability distribution of Martian rocks mechanical property for the success of Mars exploration. In this paper, a fast and accurate probability distribution method for predicting the macroscale elastic modulus of Martian rocks was proposed by integrating the microscale rock mechanical experiments (micro-RME), accurate grain-based modeling (AGBM) and upscaling methods based on reliability principles. Firstly, the microstructure of NWA12564 Martian sample and elastic modulus of each mineral were obtained by micro-RME with TESCAN integrated mineral analyzer (TIMA) and nanoindentation. The best probability distribution function of the minerals was determined by Kolmogorov-Smirnov (K-S) test. Secondly, based on best distribution function of each mineral, the Monte Carlo simulations (MCS) and upscaling methods were implemented to obtain the probability distribution of upscaled elastic modulus. Thirdly, the correlation between the upscaled elastic modulus and macroscale elastic modulus obtained by AGBM was established. The accurate probability distribution of the macroscale elastic modulus was obtained by this correlation relationship. The proposed method can predict the probability distribution of Martian rocks mechanical property with any size and shape samples.

As triboelectric nanogenerator (TENG) technology continue to evolve, its application in harsh environments has increasingly captivated the interest of researchers. However, the current research on heat-resistant triboelectric materials remains predominantly focused on the development of tribo-negative materials, with scant attention given to their equally crucial tribo-positive counterparts. In this study, the tribo-positive polyimide (PI) material with enhanced tribo-positivity is developed by integrating amide groups with electron-donating effects into the molecular chain. Furthermore, the TENG devices based on this series of tribo-positive PI materials have demonstrated an open-circuit voltage (VOC) of 242 V, a short-circuit current (ISC) of 8.13 μA, and a transferred charge (QSC) of 117 nC. Notably, these devices also demonstrate the capability to efficiently generate electricity even under elevated temperature conditions. This work not only proposes a potential molecular design strategy for developing high-performance tribo-positive PI materials applicable in TENGs, but also markedly propels the advancement of robust energy-harvesting devices engineered for operation at elevated temperatures.

Biofoam products have attracted considerable attention lately because there is a growing demand for green/sustainable products. To this end, various biobased foams have either been developed or are currently in development, e.g., bio-based polyurethanes (PUs), polylactic acid (PLA), starch, and polyhydroxyalkanotates (PHAs). Indeed, significant progress has been made; however, challenges still persist, for example, biobased foam products have poor processability, inferior compatibility, thermal and strength properties. In this review, we focus on five biofoam products: namely bio-based PUs, PLA, starch, PHAs, and cellulose biofoam products, along with their properties and performance, as well as their manufacturing processes. Further efforts are still needed to unlock the full potential of these bio-based products and meet the goal of complementing and gradually replacing some of their fossil-based counterparts. Finally, the challenges, as well as arising opportunities of future research directions are discussed.

In recent years, jacket foundations have been increasingly employed in offshore wind farms. Their complex design comprising piles and trusses poses challenges for conducting comprehensive flow field measurements using physical experiments. Consequently, the influence of the flow field on local scour around these foundations remains unclear. Therefore, numerical simulation methods are essential to depict the surrounding flow characteristics. This study utilizes large eddy simulation (LES) turbulence models within OpenFOAM to simulate the flow field around jacket foundations on flat-bed and equilibrium scour bathymetry. A flume experiment was conducted for numerical model establishment and validation. The close agreement between experimental and numerical results indicates that the LES model accurately reflects the flow patterns around the jacket foundation. Time-averaged and instantaneous flow characteristics, average kinetic energy (AKE), turbulence structure, and bed shear stress were analyzed. The results indicate that flow intensity is reduced due to the shielding effect and energy dissipation by the truss structure of the jacket foundation. Furthermore, the AKE of the flow upstream of the rear piles decreases by 18.9% in the flat-bed state and 28.0% in the equilibrium state, indicating more energy dissipation and less scour at the rear piles in the equilibrium state. The research findings offer valuable insights into the design and scour protection strategies for jacket foundations.

The semi-circular breakwater (SBW) has been implemented at numerous global locations due to its outstanding wave dissipation effectiveness and high structural performance. This study extends prior research by investigating the seabed dynamic response and hydrodynamic response characteristics around perforated SBWs. A coupled numerical model is developed to integrate waves, a semi-circular breakwater, and a sandy seabed. Wave behavior is simulated using Reynolds-averaged Navier–Stokes equations with a k-ε turbulence closure scheme, and the seabed response is numerically simulated using Biot’s full-dynamic (u-w) equations. After verifying computational accuracy, a series of tests is conducted to explore the effects of marine environments and SBW characteristics. Test results reveal a positive correlation between seabed response and wave height, wave period, and perforation number, while showing a negative correlation between seabed response and water depth and perforation rate. The basic perforation type is more effective than front and rear perforation types in maintaining a stable flow field and seabed response. These findings provide insights for designing SBWs for effective wave dissipation and seabed stability in complex marine environments, offering valuable recommendations for future designs.

The rapid development of internet technology has brought convenience to people’s lives, increasingly making their work and personal activities inseparable from the internet. However, the various types of information data in the Internet are very large, and accurately obtaining useful information from them has become particularly important. Therefore, clustering analysis technology is widely applied in various fields. The elastic network algorithm is vulnerable to noise and other factors in clustering analysis, resulting in low accuracy of clustering results. To solve this problem, this study proposes an elastic network algorithm based on weighted properties for clustering analysis. After comparative experiments, the results showed that the accuracy of the proposed algorithm was 98%. The area under the precision recall curve was 0.86. The maximum F-value was 0.93. The area under the working characteristic curve of the subject was 0.94. The precision ultimately stabilized at 97%. All values were higher than the comparison algorithm. In the experiment, the running time of the algorithm was 11 seconds and the average error was 7%, both of which were lower than the comparison algorithm. When the algorithm was affected by Statistical dispersion and threshold parameters, the accuracy of the proposed algorithm was 71%, 69% and 67% respectively, which were better than the comparison algorithm. In conclusion, the proposed elastic network algorithm based on the weighted characteristics has high accuracy, strong stability and advantages in clustering.

Abstract Background Grain length (GL) that is directly associated with appearance quality is a key target of selection in rice breeding. Although abundant quantitative trait locus (QTL) associated with GL have been identified, it was still relatively weak to identify QTL for GL from japonica genetic background, as the shortage of japonica germplasms with long grains. We performed QTLs analysis for GL using a recombinant inbred lines (RILs) population derived from the cross between japonica variety GY8 (short grains) and LX1 (long grains) in four environments. Results A total of 197 RILs were genotyped with 285 polymorphic SNP markers. Three QTLs qGL5.3, qGL6.1 and qGL11 were detected to control GL by individual environmental analyses and multi-environment joint analysis. Of these, a major-effect and stable QTL qGL6.1 was identified to be a novel QTL, and its LX1 allele had a positive effect on GL. For fine-mapping qGL6.1, a BC1F2 population consisting of 2,487 individuals was developed from a backcross between GY8 and R176, one line with long grain. Eight key informative recombinants were identified by nine kompetitive allele specific PCR (KASP) markers. By analyzing key recombinants, the qGL6.1 locus was narrowed down to a 40.41 kb genomic interval on chromosome 6. One candidate gene LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) was finally selected based on the difference in the transcriptional expression and variations in its upstream and downstream region. Conclusions Three QTLs qGL5.3, qGL6.1 and qGL11 were identified to control grain length in rice. One novel QTL qGL6.1 was fine mapped within 40.41 kb region, and LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) may be its candidate gene. We propose that the further cloning of the qGL6.1 will facilitate improving appearance quality in japonica varieties.

Objective: To explore the potential mechanism of intervention on the immune imbalance of atopic dermatitis (AD) by studying the effects of Mahuang Lianqiao Chixiaodou decoction (MLCD) on skin damage and inflammation factors in an AD-like mouse model. Methods: Ninety-six male BALB/c mice were divided into normal, model, positive control (mometasone furoate), and traditional Chinese medicine treatment (MLCD) groups by a random number table. 2,4-dinitrofluorobenzene was used to induce AD-like mice in all groups except the normal group. The treatment or intervention was administered for seven consecutive days on days 4, 18, 32, and 39. The mRNA relative expressions of interleukin-4 (IL-4), IL-10, interferon-γ (IFN-γ), thymic stromal lymphopoietin (TSLP), and the TSLP receptor (TSLPR) were measured using quantitative real-time polymerase chain reaction, and the serum immunoglobulin E, IL-4, IL-10, and IFN-γ levels were detected using enzyme-linked immunosorbent assay. Results: Compared with the normal group, the hematoxylin-eosin staining of the skin lesions of the mice in the model group was significantly thickened on days 11, 25, and 39. Compared with the model group, the epidermal thickness of the positive control group was significantly alleviated on day 39 (P

Abstract Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.

This paper begins by exploring the challenge of event-triggered state estimations in nonlinear systems, grappling with packet dropout and correlated noise. A communication mechanism is introduced that determines whether to transmit measurement values based on whether event-triggered conditions are violated, thereby minimizing redundant communication data. In designing the filter, noise decorrelation is initially conducted, followed by the integration of the event-triggered mechanism and the unreliable network transmission system for state estimator development. Subsequently, by combining the three-degree spherical–radial cubature rule, the numerical implementation steps of the proposed state estimation framework are outlined. The performance estimation analysis highlights that by adjusting the event-triggered threshold appropriately, the estimation performance and transmission rate can be effectively balanced. It is established that when there is a lower bound on the packet dropout rate, the covariance matrix of the state estimation error remains bounded, and the stochastic stability of the state estimation error is also confirmed. Ultimately, the algorithm and conclusions that are proposed in this paper are validated through a simulation example of a target tracking system.

The mutual influence between information and infectious diseases during the spreading process is becoming increasingly prominent. To elucidate the impact of factors such as higher-order interactions, interpersonal distances, and asymptomatic carriers on the coupled propagation of information and infectious diseases, a novel coupled spreading model is constructed based on a two-layer complex network, where one layer is a higher-order network and another layer is a weighted network. The higher-order interactions in information propagation are characterized using a 2-simplex, and a sUARU (simplicial unaware-aware-removed-unaware) model is employed to articulate information propagation. The inter-individual social distances in disease propagation are represented by the weights of a weighted network, and an SEIS (susceptible-exposed-infected-susceptible) model is utilized to describe disease propagation. The dynamic equations of coupled spreading are formulated utilizing the microscopic Markov chain approach. An analytical expression for the epidemic threshold is obtained by deriving it from the steady-state form of the dynamic equations. Comprehensive simulations are conducted to scrutinize the dynamic characteristics of the coupled spreading model. The findings indicate that enhancing the effects of higher-order interactions in information propagation and increasing inter-individual social distances both lead to higher outbreak thresholds and greater spreading of diseases. Additionally, a stronger infectivity among asymptomatic carriers and an extended incubation period are favorable for the outbreak and spread of an epidemic. These findings can provide meaningful guidance for the prevention and control of real-world epidemics.

Abstract A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.

Abstract Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, tumor cells show various adaptive characteristics, such as changes in the expression of cancer hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) and more frequent cell communication. Because of the adaptation of cancer cells to hypoxia, exploring the association between cell communication mediators and hypoxia has become increasingly important. Exosomes are important information carriers in cell-to-cell communication. Abundant evidence has proven that hypoxia effects in the TME are mediated by exosomes, with the occasional formation of feedback loops. In this review, we equally focus on the biogenesis and heterogeneity of cancer-derived exosomes and their functions under hypoxia and describe the known and potential mechanism ascribed to exosomes and hypoxia. Notably, we call attention to the size change of hypoxic cancer cell-derived exosomes, a characteristic long neglected, and propose some possible effects of this size change. Finally, jointly considering recent developments in the understanding of exosomes and tumors, we describe noteworthy problems in this field that urgently need to be solved for better research and clinical application.

Nanotechnologies are being increasingly widely used in advanced energy fields. Triboelectric nanogenerators (TENGs) represent a class of new-type flexible energy-harvesting devices with promising application prospects in future human societies. As one of the most important parts of TENG devices, triboelectric materials play key roles in the achievement of high-efficiency power generation. Conventional polymer tribo-negative materials, such as polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), and the standard polyimide (PI) film with the Kapton® trademark based on pyromellitic anhydride (PMDA) and 4,4′-oxydianiline (ODA), usually suffer from low output performance. In addition, the relationship between molecular structure and triboelectric properties remains a challenge in the search for novel triboelectric materials. In the current work, by incorporating functional groups of trifluoromethyl (–CF3) with strong electron withdrawal into the backbone, a series of fluorine-containing polyimide (FPI) negative friction layers have been designed and prepared. The derived FPI-1 (6FDA-6FODA), FPI-2 (6FDA-TFMB), and FPI-3 (6FDA-TFMDA) resins possessed good solubility in polar aprotic solvents, such as the N,N-dimethylacetamide (DMAc) and N-methyl-2-pyrrolidone (NMP). The PI films obtained via the solution-casting procedure showed glass transition temperatures (Tg) higher than 280 °C with differential scanning calorimetry (DSC) analyses. The TENG prototypes were successfully fabricated using the developed PI films as the tribo-negative layers. The electron-withdrawing trifluoromethyl (–CF3) units in the molecular backbones of the PI layers provided the devices with an apparently enhanced output performance. The FPI-3 (6FDA-TFMDA) layer-based TENG devices showcased an especially impressive open-circuit voltage and short-circuit current, measuring 277.8 V and 9.54 μA, respectively. These values were 4~5 times greater when compared to the TENGs manufactured using the readily accessible Kapton® film.

Objective: To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis (AD). Methods: Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group, model group, whole formula group (WF), exterior-releasing formula group (ERF), interior-clearing formula group (ICF), and positive control group (PC). A mouse model of AD was established using the semi-antigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and pH, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin, and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction. Results: Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly. Conclusions: Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Background: Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated.Methods: An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored.Results: After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1β.Conclusion: Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders.

Abstract Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.

Gastrointestinal (GI) disorders comprise a diverse range of conditions that can significantly reduce the quality of life and can even be life-threatening in serious cases. The development of accurate and rapid detection approaches is of essential importance for early diagnosis and timely management of GI diseases. This review mainly focuses on the imaging of several representative gastrointestinal ailments, such as inflammatory bowel disease, tumors, appendicitis, Meckel’s diverticulum, and others. Various imaging modalities commonly used for the gastrointestinal tract, including magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT), and photoacoustic tomography (PAT) and multimodal imaging with mode overlap are summarized. These achievements in single and multimodal imaging provide useful guidance for improved diagnosis, staging, and treatment of the corresponding gastrointestinal diseases. The review evaluates the strengths and weaknesses of different imaging techniques and summarizes the development of imaging techniques used for diagnosing gastrointestinal ailments.

To overcome the detrimental effect of residual stress in welded joints, which affects the overall performance of the welded structure, this paper studies the magnitude and distribution of residual stress after welding and local post-weld heat treatment (PWHT). The coupled thermo-metallurgical-mechanical model for welding 6 mm thick Ti-6Al-4V (TC4) titanium alloy plates was established, the evolution of the SSPT and its effect on the residual stress were quantitatively analyzed, and a parametric analysis of local PWHT was performed. The results demonstrated that there was good agreement between the numerical results and the experimental data. Due to the cooling rate reaching 327 °C/s, the volume fraction of α、 in the fusion zone (FZ) reached 0.218 after welding and decreased by 90.83% after PWHT when the heating temperature was 700 °C. The peak value of the longitudinal residual stress can reach 686.4 MPa after welding with SSPT, which was 11.38% lower than that without SSPT, and it decreased by 65.6% after PWHT when the heating temperature was 900 °C. The research results demonstrate that SSPT has a significant effect on residual stress, and PWHT can obviously reduce the residual stress, which provides a certain reference for welding TC4 titanium alloy plates.

In order to reduce the sea clutter interference in the detection of sea surface targets, we propose a bistatic sea clutter suppression method based on compressed sensing optimization in this paper. The proposed method mitigates the interference effect by reconstructing and cancelling out the sea clutter. Since the fixed sparse base is not always completely applicable for the sparse representation of sea clutter, we propose a sparse base optimization algorithm based on transfer learning to convert the fixed sparse base into an adaptive one. Moreover, we introduce a sensing matrix optimization algorithm to decrease the cross-correlation coefficient between the measurement matrix and the sparse base matrix, which can enhance the signal reconstruction quality. Finally, we use the orthogonal matching pursuit algorithm to reconstruct the sea clutter and employ the reconstructed results to cancel and suppress the sea clutter. The simulation results demonstrate that the proposed method outperforms the traditional methods such as the root time-domain cancellation method and the singular value decomposition method (SVD). Therefore, the proposed method has great practical significance for the detection of bistatic sea surface targets.

Abstract Molecular oxygen (O2) is a universal electron acceptor that is eventually synthesized into ATP in the mitochondrial respiratory chain of all metazoans. Therefore, hypoxia biology has become an organizational principle of cell evolution, metabolism and pathology. Hypoxia-inducible factor (HIF) mediates tumour cells to produce a series of glucose metabolism adaptations including the regulation of glucose catabolism, glycogen metabolism and the biological oxidation of glucose to hypoxia. Since HIF can regulate the energy metabolism of cancer cells and promote the survival of cancer cells, targeting HIF or HIF mediated metabolic enzymes may become one of the potential treatment methods for cancer. In this review, we summarize the established and recently discovered autonomous molecular mechanisms that can induce cell reprogramming of hypoxic glucose metabolism in tumors and explore opportunities for targeted therapy.

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies.

Variable damping shock absorbers have received extensive attention for their efficient vibration reduction performance, and air springs have also been widely used in high-end commercial vehicles due to their nonlinear stiffness characteristics. This paper presents a novel semi-active cab suspension integrated with an air spring and a variable damping electromagnetic damper (A-EMD). The electromagnetic damper (EMD) prototype was designed, manufactured and tested. Then, due to the interference of nonlinear stiffness characteristics of the air spring with the controller in the subsequent design, the Takagi–Sugeno fuzzy method was adopted to segmentally linearize its nonlinearity, based on which an H∞ state feedback semi-active controller was designed to control the EMD to generate variable damping force. Furthermore, a Luenberger state observer was designed to provide immeasurable state parameters for the controller. Numerical simulations were carried out to validate the effectiveness of the proposed approaches, and the results show that the proposed control strategy can significantly improve the ride comfort of the A-EMD system. The vibration dose value (VDV) acceleration under the bump road and the frequency-weighted acceleration root mean square (FWA-RMS) under the random road decreased by 36.05% and 19.77%, respectively, compared with the passive suspension system.

In this paper, a discrete element method (DEM) is used to simulate the suction process of fresh concrete in the pumping system, and the influence of the stirring blade on the suction is explored. The Hertz-Mindlin with JKR Cohesion contact model is used to establish the DEM model of fresh concrete, and the suction work is realized by an API function of DEM, and the movement of particles in the suction cylinder can be completed smoothly. The changes of the concrete flow field during the suction process are further studied, and the influence mechanism of the stirring blade on the suction process is explained. A numerical simulation scheme is designed to explore the influence of the rotation speed, installation angle, and edges distance of the stirring blade on the suction efficiency and the stirring resistance torque, and the structure of the stirring blade is optimized according to the influence law. The simulation results show that the stirring resistance torque of the optimized stirring blade is reduced without the suction efficiency of the pumping system reduced, and the stirring energy consumption of the pump suction is reduced.

PurposeSorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC.MethodsBioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions.ResultsCISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened.ConclusionInhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.

Intelligent connected electric vehicles (EVs) are widely considered as a trend in the global automotive industry to make transportation safer, cleaner and more comfortable. As an important component of intelligent connected EVs, the brake-by-wire (BBW) system is the key to determining the performance of the vehicle and the efficiency of braking energy recovery. BBW systems are showing great promise in the area of vehicle braking due to the increasing requirements on safety and energy efficiency of vehicles. In recent years, BBW systems have undergone great changes in terms of structure and control methods, not only increasing safety and energy recovery efficiency, but also integrating more functions. Although important advancements have been achieved in this field, these works have not been fully summarised. This paper surveys and summarizes the research in literature to bring topical information to the field of intelligent transportation systems. The objective of this study is to present an overview of both the development trend and key technologies of the BBW system for intelligent connected EVs. Firstly, the development, structure and core components of BBW system are described. Secondly, the control method and control strategy of BBW system are analyzed. As much as the system shows great promise, the problems existing on its current technology should be addressed as well. Finally, some important countermeasures are proposed to solve the existing technical problems of the BBW system.

Abstract Background Emerging evidence indicates that tumor cells release a large amount of exosomes loaded with cargos during tumorigenesis. Exosome secretion is a multi-step process regulated by certain related molecules. Long non-coding RNAs (lncRNAs) play an important role in hepatocellular carcinoma (HCC) progression. However, the role of lncRNA HOTAIR in regulating exosome secretion in HCC cells remains unclear. Methods We analyzed the relationship between HOTAIR expression and exosome secretion-related genes using gene set enrichment analysis (GSEA). Nanoparticle tracking analysis was performed to validate the effect of HOTAIR on exosome secretion. The transport of multivesicular bodies (MVBs) after overexpression of HOTAIR was detected by transmission electron microscopy and confocal microscopy analysis of cluster determinant 63 (CD63) with synaptosome associated protein 23 (SNAP23). The mechanism of HOTAIR’s regulation of Ras-related protein Rab-35 (RAB35), vesicle associated membrane protein 3 (VAMP3), and SNAP23 was assessed using confocal co-localization analysis, phosphorylation assays, and rescue experiments. Results We found an enrichment of exosome secretion-related genes in the HOTAIR high expression group. HOTAIR promoted the release of exosomes by inducing MVB transport to the plasma membrane. HOTAIR regulated RAB35 expression and localization, which controlled the docking process. Moreover, HOTAIR facilitated the final step of fusion by influencing VAMP3 and SNAP23 colocalization. In addition, we validated that HOTAIR induced the phosphorylation of SNAP23 via mammalian target of rapamycin (mTOR) signaling. Conclusion Our study demonstrated a novel function of lncRNA HOTAIR in promoting exosome secretion from HCC cells and provided a new understanding of lncRNAs in tumor cell biology.

Abstract Background Anopheles sinensis is the primary vector of vivax malaria in China and its control is under great threat as the development of insecticide resistance. In contrast to physiological resistance, there is no report of behavioural modifications of resistant An. sinensis after long-term insecticide use, despite their huge potential impact on malaria transmission. Methods Larvae or pupae of An. sinensis were collected from Yuanyang, Bishan, and Wuhe counties from southwestern to eastern China. Resistance to deltamethrin was assayed using the standard World Health Organization (WHO) susceptibility test. The frequency distribution of the kdr allele of the para-type sodium channel gene was determined by polymerase chain reaction (PCR) amplification and DNA sequencing. Contact repellency to deltamethrin-impregnated bed nets was evaluated using a modified WHO cone bioassay. Results All contemporary field populations for all three geographic locations were resistant to deltamethrin, with mortality ranging from 6.00 to 26.79%. Three kdr genotypes with either an L1014F or L1014C substitution with frequencies of 76.10–100% were identified in the Bishan and Wuhe populations, but no kdr mutations were detected in the Yuanyang samples despite high phenotypic resistance. The susceptible mosquitoes exhibited significantly longer flying time and more takeoffs on deltamethrin-treated bed nets (DTN) than on untreated bed nets (UTN), suggestive of robust avoidance behaviour. However, no significant increases in the frequency of takeoffs or flying time were observed in deltamethrin-resistant An. sinensis populations when exposed on DTNs, regardless of the presence of a kdr mutation. Moreover, the first takeoff from DTNs by resistant mosquitoes significantly lagged behind compared to susceptible mosquitoes. Conclusion The An. sinensis populations were highly resistant to deltamethrin and exhibited decreased avoidance behaviour. Behavioural modification significantly associated with deltamethrin resistance, but not directly related to the presence of kdr mutations, indicating that there are additional factors contributing to the changes.

This paper proposes an analytical solution and isogeometric analysis numerical approach for buckling analysis of size-dependent beams based on a reformulated strain gradient elasticity theory (RSGET). The superiority of this method is that it has only one material parameter for couple stress and another material parameter for strain gradient effects. Using the RSGET and the principle of minimum potential energy, both non-classical Euler–Bernoulli and Timoshenko beam buckling models are developed. Moreover, the obtained governing equations are solved by an exact solution and isogeometric analysis approach, which conforms to the requirements of higher continuity in gradient elasticity theory. Numerical results are compared with exact solutions to reveal the accuracy of the current isogeometric analysis approach. The influences of length–scale parameter, length-to-thickness ratio, beam thickness and boundary conditions are investigated. Moreover, the difference between the buckling responses obtained by the Timoshenko and Euler–Bernoulli theories shows that the Euler–Bernoulli theory is suitable for slender beams.

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.

This paper presents a novel non-classical Timoshenko–Ehrenfest beam model based on a reformulated strain gradient elasticity theory. The strain gradient effect, couple stress effect, and velocity gradient effect for vibration are included in the new model by only one material length scale parameter for each. The variational formulation and Hamilton’s principle are applied to derive the governing equations and boundary conditions. Both an analytical solution and an isogeometric analysis approach are proposed for static bending and free vibration of the microbeam. A non-uniform rational B-splines (NURBS) isogeometric analysis with high-order continuity can effectively fulfill the higher derivatives of the displacement variables in the reformulated gradient beam model. Convergence studies and comparisons to the corresponding analytical solutions verify the model’s performance and accuracy. Finally, different boundary conditions, material length scale parameters, and beam thicknesses are investigated in order to certify the applicability of the proposed approach.

China is located in the intersection area of two seismic zones. Due to this special geographical location, earthquake disasters occur frequently in China. Earthquake emergency rescue work is one of the key construction works of disaster prevention and mitigation in China. This paper mainly studies the earthquake disaster rescue model based on the complex adaptive system theory and establishes the earthquake disaster rescue model by analyzing the complex adaptive system theory and combining the earthquake rescue process. In this paper, through the task allocation mechanism task, the disaster rescue task is divided into simple task and complex task, and the executive task subject is divided into single task subject and multitask subject. On the basis of considering the shortest emergency rescue time goal and the goal of maximizing the deployment utility of rescue team, the reasonable deployment of a rescue team is realized through a complex adaptive system, that is, the deployment utility of the rescue team is maximized. In this paper, the simulation experiment and comparison of the earthquake disaster rescue model based on the complex adaptive system theory are carried out. The experimental results show that the model used in this paper is better than the other two models in terms of algorithm convergence, rescue number, and overall score; in different scenarios, the relative survival probability of the model in this paper is 58.92%, 67.85%, and 77.46%, and the proportion of the wounded rescued is 66.31%, 76.45%, and 83.06%, which were higher than those of the other two models. The earthquake disaster rescue model based on the complex adaptive system theory proposed in this paper provides an effective theoretical basis and method system for postdisaster emergency rescue decision making and enhances and improves the emergency response ability to deal with large-scale geological disaster events.

The Chinese text classification task is challenging compared to tasks based on other languages such as English due to the characteristics of the Chinese text itself. In recent years, some popular methods based on deep learning have been used for text classification, such as the convolutional neural network (CNN) and the long short-term memory (LSTM) network. However, some problems are still encountered when classifying Chinese text. For example, important but obscure context information in Chinese text is not easily extracted. To improve the effect of Chinese text classification, we propose a novel classification model in this paper named the hierarchical comprehensive context modeling network (HCCMN) that can extract more comprehensive context. Our approach aims to extract contextual information and integrate it with the original input and then extract hierarchically more context, spatial information and high-weight local features from the integrated results. In addition, our method can remember long-term historical obscure information. Since Chinese radiology texts are complicated and difficult to obtain, we collected a Chinese radiology medical text dataset (CIRTEXT) containing more than 56,000 real-world data samples to verify the effect of this work. We conducted experiments on four datasets and showed that our HCCMN performs at state-of-the-art levels on three selected evaluation metrics compared to baselines. We present promising results showing that our hierarchical context modeling network extracts useful context from Chinese text more effectively and comprehensively.

The low mechanical efficiency of metal belt’s continuously variable transmission (CVT) limits its application in new energy vehicles. To further improve CVT efficiency and reduce the energy consumption of electric vehicles (EVs) with CVT, this paper proposes a pure electric CVT configuration and a clamping force control strategy. The slip characteristics of CVT are obtained through a bench test, the dynamic model of CVT slip is established, and a clamping force fuzzy control strategy is designed. The strategy is studied by simulation under extreme conditions and standard driving cycles. The simulation results show that the proposed clamping force control strategy has good adaptability. Under extreme conditions, this strategy can ensure that CVT does not undergo macro slip, while reducing the clamping force by 12.86–21.65%. Energy consumption per 100 km is 14.90 kWh in NEDC, which is 6.67% lower compared with the traditional strategy. CVT average efficiency and average transmission efficiency increased by 3.71% and 6.40%. The research results demonstrate that adjusting the CVT clamping force through fuzzy control based on the slip rate can improve the CVT efficiency and energy economy of EVs, which provides a certain reference for CVT clamping force control strategy development and the application of CVT on EVs.

Abstract Background Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H+ clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation. Methods Autophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription–PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues. Results Autophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3). Conclusion Activation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.

Based on our innovative application of using thick continuous casting slab 0.4C1.5Mn2Cr0.35Mo1.5Ni (high alloy) for the production of high-quality mould steel, the present study investigated the high cracking susceptibility of high-alloy steel and segregation in continuous casting slab. The thermal expansion and the continuous cooling transformation (CCT) curve measurement, together with a high temperature in situ observation, confirmed the martensite phase transition happening at approximately 583 K that would result in an increase in the hardenability and cracking susceptibility. The cracking susceptibility zone was determined by high-temperature mechanical properties measurement. The high-alloy mould steel has no II brittle zone, and III brittle zone is 973–1148 K. As a conclusion, the straightening temperature should be above 1148 K to avoid the cracking during the continuous casting. Moreover, the elemental segregation of carbon, sulfur, chromium, and molybdenum along the cracking was examined by electron probe microanalysis (EPMA) quantitative analysis that might be another reason for the steel crack formation. It shows that Martensite phase transition happened at approximately 583 K that would result in an increase in the hardenability and cracking susceptibility.

Polymeric nanofibrous membranes (NFMs) with both high whiteness and high thermal and ultraviolet (UV) stability are highly desired as reflectors for ultraviolet light-emitting diodes (UV-LEDs) devices. In the current work, a semi-alicyclic and fluoro-containing polyimide (PI) NFM with potential application in such kinds of circumstances was successfully fabricated from the organo-soluble PI resin solution via a one-step electrospinning procedure. In order to achieve the target, a semi-alicyclic PI resin was first designed and synthesized from an alicyclic dianhydride, 3,4-dicarboxy-1,2,3,4,5,6,7,8-decahydro-1-naphthalenesuccinic dianhydride (or hydrogenated tetralin dianhydride, HTDA), and a fluoro-containing diamine, 2,2-bis[4-(4-amino-phenoxy)phenyl]hexafluoropropane (BDAF), via an imidization procedure. The derived PI (HTDA-BDAF) resin possessed a number-average molecular weight (Mn) higher than 33,000 g/mol and was highly soluble in polar aprotic solvents, such as N,N-dimethylacetamide (DMAc). The electrospinning solution was prepared by dissolving the PI resin in DMAc at a solid content of 25–35 wt%. For comparison, the conventional high-whiteness polystyrene (PS) NFM was prepared according to a similar electrospinning procedure. The thermal and UV stability of the derived PI and PS NFMs were investigated by exposure under the UV-LED (wavelength: 365 nm) irradiation. Various thermal evaluation results indicated that the developed PI (HTDA-BDAF) NFM could maintain both the high reflectance and high whiteness at elevated temperatures. For example, after thermal treatment at 200 °C for 1 h in air, the PI (HTDA-BDAF) NFM exhibited a reflectance at a wavelength of 457 nm (R457) of 89.0%, which was comparable to that of the pristine PI NMF (R457 = 90.2%). The PI (HTDA-BDAF) NFM exhibited a whiteness index (WI) of 90.88, which was also close to that of the pristine sample (WI = 91.22). However, for the PS NFM counterpart, the R457 value decreased from the pristine 88.4% to 18.1% after thermal treatment at 150 °C for 1 h, and the sample became transparent. The PI NFM maintained good optical and mechanical properties during the high dose (2670 J/cm2) of UV exposure, while the properties of the PS NFM apparently deteriorated under the same UV aging.

Farnesoid X receptor (FXR) and related pathways are involved in the therapeutic effect of sleeve gastrectomy for overweight or obese patients with diabetes mellitus. This study aimed to investigate the mechanism of FXR expression regulation during the surgical treatment of obese diabetes mellitus by sleeve gastrectomy. Diabetic rats were established by combined streptozotocin and high-fat diet induction. Data collection included body weight, chemical indexes of glucose and lipid metabolism, liver function, and the expression levels of musculoaponeurotic fibrosarcoma oncogene family B (MAFB), FXR, and related genes induced by sleeve gastrectomy. Chang liver cells overexpressing MAFB gene were established to confirm the expression of related genes. The binding and activation of FXR gene by MAFB were tested by Chip and luciferase reporter gene assays. Vertical sleeve gastrectomy induced significant weight loss and decreased blood glucose and lipids in diabetic rat livers, as well as decreased lipid deposition and recovered lipid function. The expression of MAFB, FXR, and FXR-regulated genes in diabetic rat livers were also restored by sleeve gastrectomy. Overexpression of MAFB in Chang liver cells led to FXR gene expression activation and the alteration of multiple FXR-regulated genes. Chip assay showed that MAFB could directly bind with FXR promoter, and the activation of FXR expression was confirmed by luciferase reporter gene analysis. The therapeutic effect of sleeve gastrectomy for overweight or obese patients with diabetes mellitus was mediated by activation of FXR expression through the binding of MAFB transcription factor.

Background/Aims: The molecular mechanisms of celastrol on hepatocellular carcinoma (HCC) cells migration and invasion ability is the major problem that prompted the study. Methods: We first evaluated the effect of celastrol on migration and invasion ability of HepG2 cells using transwell migration and matrigel invasion assays. Next, we assessed the effect of celastrol on NF-κB transcriptional activity in hepatocellular carcinoma cells using western blot and luciferase reporter assay. We also performed real-time PCR to measure miR-224, MMP-2 and MMP-9 expression. Western blot was used to measure protein expression of MMP-2 and MMP-9. Furthermore, we used miR-224 inhibitor to evaluate whether down-regulation of miR-224 expression can affect MMP-2 and MMP-9 expression. The binding ability of p65/NF-κB on the miR-224 promote has been assessed by chromatin immunoprecipitation and quantitative real-time PCR (ChIP-qPCR). Finally, we evaluated the effect of miR-224 on celastrol-induced anti-tumor activity using miR-224 precursor. Results: Celastrol significantly impaired migration and invasion of HepG2 cells and inhibited the activation of NF-κB and Akt in dose-dependent manner. IGF (the strong stimulator of Akt) inhibited the transcriptional activity of NF-κB in cells treated with celastrol. Besides, celastrol efficiently decreased the expression of miR-224 and protein expression of MMP-2 and MMP-9. ChIP-qPCR showed that p65/NF-κB binding to the miR-224 promoter sharply decreased after exposure to celastrol in time-dependent manner. Furthermore, inhibition of miR-224 expression can decrease MMP-9 protein level. Most importantly, miR-224 precursor can reverse the effect of celastrol on impairment of migration and invasion in HepG2 and Huh7 cells. Conclusion: Celastrol treatment inhibits migration and invasion of HCC cell and that the effect is partly due to NF-κB regulating miR-224 expression.

Rare earth (RE) addition can refine and change the shape/distribution of inclusions in steel to improve its strength and toughness. In this paper, the control of RE, specifically Ce and La, and their behaviors in the practical industrial production of high-strength structural steel with 420 MPa yield strength were studied. In particular, the interactions between RE and Al, Nb, S, O were investigated, with the aim of improving the steel toughness and welding performance. The impact energy of the plate with RE is approximately 50 J higher than the regular plate without RE. The toughness of the plate from ladle furnace (LF) refining with RE addition is better than the one from Ruhrstahl and Hereaeus (RH) refining. The RE inclusions could induce the intragranular ferrite and refine the grain size to the preferred size. After welding at the heat input of 200 kJ/cm, the grain size at the heat affected zone was found to be the finest in the plate from the LF process with RE addition. Notably, the microstructure of ferrite was quasi-polygonal.

Due to lack of visualization experiment on the mechanism of electrorheological effect in dynamic field, a visualization experimental system is designed and successfully made. Through this experiment, the submicroscopic dynamic structural changes of electrorheological (ER) fluids in the coupling field composed by external electric field and flow field are observed. The experimental results indicate that the rheological behaviors of ER fluids are mainly influenced by the polarization forces and the hydrodynamic forces in the dynamic coupling field. And the experiment shows that the yield fracture of chain structures determined the yield strength of ER fluids firstly occurring near the plate electrodes, which expresses the microflow characteristic of velocity slip. Meanwhile, the capture effect has been verified in this experiment.

With the development of automotive vibration technology, the semiactive suspension system with adjustable damping force and high reliability is taken seriously. The magnetorheological damper (MRD) that applies intelligent material (magnetorheological fluid) is the key element of this system. It can achieve a continuous and adjustable damping and then reaches the purpose of comfort. In order to improve the damping effect of MRD, this paper presents a MRD, which has magnetorheological (MR) effect along annular radial channel. The paper completely designs the structure and magnetic circuit of MRD. Based on the theory of electromagnetism and MR fluid dynamics, the paper analyzes and tests the external characteristics of the MRD by the MATLAB/Simulink and the vibration experiment. The results compared with ordinary MRD reveal that the damping force obviously increases and has wide adjustable range, thus verifying the reasonableness of the damper design.

Background. Laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy for treating congenital choledochal cysts (CCCs) have proved to be efficacious in children. Its safety and efficacy in adult patients remain unknown. The purpose of this study was to determine whether the laparoscopic procedure was feasible and safe in adult patients. Methods. We reviewed 35 patients who underwent laparoscopic operation (laparoscopic group) and 39 patients who underwent an open procedure (open group). The operative time, intraoperative blood loss, time until bowel motion recovery, duration of drainage, postoperative stay, time until resumption of diet, postoperative complications, and perioperative laboratory values were recorded and analyzed in both groups. Results. The operative time was longer in the laparoscopic group and decreased significantly with accumulating surgical experience (P0.05). Conclusions. Laparoscopic cyst excision and hepaticojejunostomy are a feasible, effective, and safe method for treating CCCs in adult patients.

BackgroundExtracellular heat shock protein 70 and peptide complexes (eHSP70/HSP70-PCs) regulate a variety of biological behaviors in tumor cells. Whether eHSP70/HSP70-PCs are involved in the epithelial-mesenchymal transition (EMT) of tumor cells remains unclear.AimsTo determine the effects of eHSP70/HSP70-PCs on EMT of hepatocarcinoma cells.MethodsThe expressions of E-cadherin, HSP70, α-smooth muscle actin protein (α-SMA) and p-p38 were detected immunohistochemically in liver cancer samples. Immunofluorescence, western blotting and real-time RT-PCR methods were used to analyze the effects of eHSP70/HSP70-PCs on the expressions of E-cadherin, α-SMA and p38/MAPK in vivo.ResultsHSP70, E-cadherin, α-SMA and p-p38 were elevated in hepatocellular carcinoma tissues. The expression of HSP70 was positively correlated with malignant differentiated liver carcinoma. The expressions of HSP70, α-SMA and p-p38 correlated with recurrence-free survival after resection. eHSP70/HSP70-PCs significantly promoted the expressions of α-SMA and p-p38 and reduced the expressions of E-cadherin in vivo. The effect was inhibited by SB203580.ConclusionThe expressions of HSP70, E-cadherin, α-SMA and p-p38 may represent indicators of malignant potential and could discriminate the malignant degree of liver cancer. eHSP70/HSP70-PCs play an important role in the EMT of hepatocellular carcinoma via the p38/MAPK pathway.

Hilar cholangiocarcinoma is a highly aggressive malignancy originating from the hilar biliary duct epithelium. Due to few effective comprehensive treatments, the prognosis of hilar cholangiocarcinoma is poor. In this study, immunohistochemistry was first used to detect and analyze the expression of Gab1, VEGFR-2, and MMP-9 in hilar cholangiocarcinoma solid tumors and the relationships to the clinical pathological features. Furthermore, Gab1 and VEGFR-2 siRNA were used to interfere the hilar cholangiocarcinoma cell line ICBD-1 and then detect the PI3K/Akt signaling pathway, MMP-9 levels and malignant biological behaviors of tumor cells. The data showed that 1. Gab1, VEGFR-2, and MMP-9 were highly expressed and positively correlated with each other in hilar cholangiocarcinoma tissues, which were related to lymph node metastasis and differentiation. 2. After Gab1 or VEGFR-2 siRNA interference, PI3K/Akt pathway activity and MMP-9 levels were decreased in ICBD-1 cells. At the same time, cell proliferation decreased, cell cycle arrested in G1 phase, apoptosis increased and invasion decreased. These results suggest that the expression of Gab1, VEGFR-2, and MMP-9 are significantly related to the malignant biological behavior of hilar cholangiocarcinoma. Gab1 regulates growth, apoptosis and invasion through the VEGFR-2/Gab1/PI3K/Akt signaling pathway in hilar cholangiocarcinoma cells and influences the invasion of tumor cells via MMP-9.