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Coal gasification technology is an effective way to the clean and efficient utilization of coal, the entrained-flow gasification process with radiant syngas cooler (RSC) can effectively recover the sensible heat from high temperature syngas and improve energy utilization rate. The radiation screen adopted inside the RSC is not only keeping the overall structure compact, but improving the heat transfer area greatly. In order to study the thermal deformation of the radiation screen in the RSC under gasification operating conditions, a three-dimensional radiation screen model is established by using the fluid-structure coupling principle to simulation analysis. The simulation results show that under normal operating conditions, the temperature of the whole water-cooling pipe reaches the maximum value at 5.30 m from the top. In the circumferential direction, the surface temperature of the pipe 1 closest to the center of the RSC is parabola distribution. Temperature in the middle of the fire-facing side is the highest, and the maximum temperature difference between the fire-facing side and its back side reaches 60 K. Due to the cooling action of adjacent water-cooling pipe, the surface temperature of pipe 2−5 becomes bimodal distribution. The spatial arrangement has direct effect on the surface temperature distribution of water-cooling pipe. The local deformation of pipe 1 closest to the center of the RSC in water-cooling pipe without fixed is the largest, which is 5.20 cm. Maximum offset in π direction is 4.58 cm, far exceeding the pitch of water-cooling pipes, and the collision between water-cooling pipes is prone to occur. The overall deformation arises after water-cooling pipe is fixed. Maximum thermal deformation of water-cooling pipe with fixed is 3.28 cm, which is 36.9% lower than that of water-cooling pipe without fixed. The relative shift in the π direction basically disappears. Local deformation between the water-cooling pipe is smaller than the distance between the pipes. The occurrence of collision between water-cooling pipes is disappeared for the fixed action of the fixture. The changes of inlet syngas temperature and surface deposition affect the surface temperature gradient and deformation of water-cooling pipe with varying degrees, the offset direction is π/2 side of the water-cooling pipe.

Perfluorobutane sulfonate (PFBS) is recognized as a highly persistent environmental contaminant, notorious for its chemical stability and enduring presence in ecosystems. Its propensity for persistence and environmental mobility allows PFBS to infiltrate the human body, predominantly accumulating in the liver where it poses a potential risk for hepatic damage. This investigation aimed to explore the outcomes of PFBS on the physiological functionalities of hepatocytes in vitro. To this end, hepatocytes were exposed to 750 ug/ml PFBS, followed by an analysis of various cellular phenotypes and functionalities, including assessments of cell viability and mitochondrial integrity. The findings indicated that PFBS exposure led to a suppression of cell proliferation and an increase in apoptotic cell death. Moreover, PFBS exposure was found to augment the generation of reactive oxygen species (ROS) and induce significant mitochondrial dysfunction. Gene expression analysis identified significant changes in genes associated with numerous tumor signaling pathways and autophagy signaling pathways. Further examinations revealed an increase in cellular mitophagy following PFBS exposure, coupled with the activation of the mitophagy-associated Drp1/Pink1/Parkin pathway. Inhibition of mitophagy was observed to concurrently amplify cellular damage and inhibit the Drp1/Pink1/Parkin pathway. Together, these findings highlight PFBS’s capacity to inflict hepatocyte injury through mitochondrial disruption, positioning Drp1/Pink1/Parkin-mediated mitophagy as a crucial cellular defense mechanism against PFBS-induced toxicity.

Coal-water slurry gasification is one of advanced coal gasification technologies. The improvement on the efficiency of coal-water slurry gasification is helpful to promote the clean and efficient utilization of coal. Coal-water slurry preheating technology is considered as one of the key technologies to improve the energy utilization efficiency of coal gasification. At present, the variation pattern and intrinsic mechanism of thermal conductivity of complex liquid-solid suspensions are still not fully understood. The thermal conductivity is an important basic parameter of the medium flow heat transfer, characterizing its thermal conductivity in the steady-state thermal conductivity process. The transient hot wire method is used to measure the thermal conductivity of the same concentration coal-water slurry at different temperatures. The experimental results show that the higher the temperature, the higher the thermal conductivity. The thermal conductivity of coal-water slurry is determined at different mass concentrations with a room temperature. The experimental results show that it can be divided into two stages: the mass concentration increases from 51% to 58% in a drop zone, and the thermal conductivity decreases rapidly, its value decreases from 0.401 W/(m·K) to 0.358 W/(m·K); and the mass concentration continues to increase from 58% to 67% in a constant zone, and the thermal conductivity basically remains at 0.358 W/(m·K). Based on the experimental results, the parallel prediction model of thermal conductivity of coal-water slurry with coal particle-bonded water composite is proposed by considering the parallel model, Maxwell model, generalized self-consistent model and other composite models. The water in coal-water slurry contains free water and bound water, and the bound water will form a coal particle-bound water composite phase with coal particles, and the coal-water slurry is regarded as a two-phase composite composed of the composite phase and the free water phase. In the drop zone, with the increase of coal particle concentration, the free water phase decreases, the composite phase remains basically unchanged, and the thermal conductivity of coal-water slurry decreases rapidly. In the constant zone, the amount of bound water in the composite phase decreases with further increase in coal particle concentration, but the thermal conductivity of the composite phase remains basically stable. The model prediction results agree well with the experimental data.

Abstract Background To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. Methods HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. Results The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from − 29.03% to 34.78%. Conclusions CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Abstract Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV‐1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2‐apex‐targeting broadly neutralizing antibody, CAP256V2LS. The resultant human‐llama bispecific antibody CAP256L‐R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV‐1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn‐Fc mice similar to the parent CAP256V2LS. Vaccine‐elicited llama nanobodies, when combined with V2‐apex broadly neutralizing antibodies, may therefore be able to fulfill anti‐HIV‐1 therapeutic and prophylactic clinical goals.

Rationale: MER proto-oncogene tyrosine kinase (MerTK) is a key receptor for the clearance of apoptotic cells (efferocytosis) and plays important roles in redox-related human diseases. We will explore MerTK biology in human cells, tissues, and diseases based on big data analytics. Methods: The human RNA-seq and scRNA-seq data about 42,700 samples were from NCBI Gene Expression Omnibus and analyzed by QIAGEN Ingenuity Pathway Analysis (IPA) with about 170,000 crossover analysis. MerTK expression was quantified as Log2 (FPKM + 0.1). Results: We found that, in human cells, MerTK is highly expressed in macrophages, monocytes, progenitor cells, alpha-beta T cells, plasma B cells, myeloid cells, and endothelial cells (ECs). In human tissues, MerTK has higher expression in plaque, blood vessels, heart, liver, sensory system, artificial tissue, bone, adrenal gland, central nervous system (CNS), and connective tissue. Compared to normal conditions, MerTK expression in related tissues is altered in many human diseases, including cardiovascular diseases, cancer, and brain disorders. Interestingly, MerTK expression also shows sex differences in many tissues, indicating that MerTK may have different impact on male and female. Finally, based on our proteomics from primary human aortic ECs, we validated the functions of MerTK in several human diseases, such as cancer, aging, kidney failure and heart failure. Conclusions: Our big data analytics suggest that MerTK may be a promising therapeutic target, but how it should be modulated depends on the disease types and sex differences. For example, MerTK inhibition emerges as a new strategy for cancer therapy due to it counteracts effect on anti-tumor immunity, while MerTK restoration represents a promising treatment for atherosclerosis and myocardial infarction as MerTK is cleaved in these disease conditions.

Abstract TJP2/ZO-2-inactivating mutations in humans cause progressive cholestatic liver disease. Liver-specific deletion of Tjp2 in the mouse (Tjp2 cKO mice) leads to mild progressive cholestasis without an overt degradation of the bile-blood barrier (BBB). These mice are more susceptible to cholic acid (CA) induced liver injury. Interestingly, while initially also more susceptible, Tjp2 cKO mice develop tolerance to a DDC-supplemented diet. The DDC diet induces an exacerbated ductular reaction in Tjp2 cKO mice, which arises from the transdifferentiation of hepatocytes to cholangiocytes. Consequently, this transdifferentiation is only observed if Tjp2 is inactivated in hepatocytes, but not if deleted in cholangiocytes. The DDC-diet-induced hepatocyte transdifferentiation in Tjp2 cKO mice requires Yap and Wwtr1/Taz, whose protein expression is upregulated in hepatocytes lacking Tjp2, but is independent of Notch2. Although inactivating Tjp2 is sufficient for the upregulation of Yap and Wwtr1/Taz protein, efficient transdifferentiation requires the DDC-diet insult. Thus, Tjp2 negatively regulates Yap/Taz-mediated transdifferentiation of hepatocytes to cholangiocytes in response to DDC-diet-induced liver injury. Furthermore, transdifferentiation is regulated at multiple levels and the type of injury inflicted on the Tjp2 deficient liver plays an important role in the resulting pathophysiology.

The identity-based encryption with equality test (IBEET) has become a hot research topic in cloud computing as it provides an equality test for ciphertexts generated under different identities while preserving the confidentiality. Subsequently, for the sake of the confidentiality and authenticity of the data, the identity-based signcryption with equality test (IBSC-ET) has been put forward. Nevertheless, the existing schemes do not consider the anonymity of the sender and the receiver, which leads to the potential leakage of sensitive personal information. How to ensure confidentiality, authenticity, and anonymity in the IBEET setting remains a significant challenge. In this paper, we put forward the concept of the identity-based matchmaking encryption with equality test (IBME-ET) to address this issue. We formalized the system model, the definition, and the security models of the IBME-ET and, then, put forward a concrete scheme. Furthermore, our scheme was confirmed to be secure and practical by proving its security and evaluating its performance.

Circulating fluidized bed (CFB) boilers are widely used in industrial production due to their high combustion efficiency, low pollutant emissions and wide load-adjustment range. However, the water-level-control system of a CFB boiler exhibits time-varying behavior and nonlinearity, which affect the control performance of the industrial system. This paper proposes a novel data-driven adaptive integral sliding-mode control (ISMC) method for the CFB control system with external disturbances. Firstly, the scheme designs a discrete ISMC law based on the full-format dynamic linearization (FFDL) data model, which is equivalent to a nonlinear system. Furthermore, a new reaching law is proposed to quickly drive the system state onto the sliding-mode surface. The improved ISMC control scheme only utilizes the input–output data during the design process and does not require model information. After theoretically verifying the stability of the method proposed in this paper, it is further applied in MIMO systems. Finally, the control and practical effects of this method are evaluated by using the DHX25-1.25 CFB boiler installed in the special-equipment testing center. The experimental results show that, compared with the traditional sliding-mode control (SMC) and model-free adaptive-control (MFAC) methods, the improved control method can quickly track the given signal and exhibit resistance to noise interference. Furthermore, it can rapidly respond to changes in the working conditions of the CFB system.

Abstract Background Previous studies reported that emodin extracted from Rheum palmatum L. exerts antiproliferation and antimetastatic effects in a variety of human cancer types. However, the role of emodin in hepatocellular carcinoma (HCC) remain unknown. Methods EdU and colony formation assays were performed to evaluate the effects of emodin on proliferation. The mobility capacities of HCC treated with emodin were evaluated using wound healing assay. Transwell invasion and migration assays were performed to evaluate anti-migratory and anti-invasive effects of emodin on HCC. Annexin V-FITC/PI was performed to analyze the apoptosis. PI stain was performed to analyze cell cycle. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) induced by emodin in HCC. The impact of emodin on autophagic flux in HepG2 cells was examined by mCherry-GFP-LC3 analysis. Western blot was used to assess the protein expressions of epithelial-mesenchymal transition (EMT), autophagy, PI3K/AKT/mTOR and Wnt/β-catenin signaling pathway. Results We found that emodin inhibited the growth of HepG2 cells in a dose- and time-dependent manner. In addition, emodin inhibited cell proliferation, induced S and G2/M phases arrest, and promoted apoptosis in HepG2 cells. The migration and invasion of HepG2 cells were also suppressed by emodin. Enrichment analysis revealed that DEGs involved in cell adhesion, cancer metastasis and cell cycle arrest. Moreover, western bolt results show that emodin-induced autophagy promotes Snail and β-catenin degradation. We also found that blocking autophagic flux after emodin treatment caused EMT reversal. Furthermore, the PI3K agonist Y-P 740 significantly reversed the phosphorylation levels of GSK3β and mTOR. These results indicated that emodin induced autophagy and inhibited the EMT in part through suppression of the PI3K/AKT/mTOR and Wnt/β-catenin pathways. Conclusion Our study indicated that emodin inhibited cell metastasis in HCC via the crosstalk between autophagy and EMT.

Similar to many complex systems, the operation process of electric balanced forklifts has characteristics such as time-varying model parameters and nonlinearity. Establishing an accurate mathematical model becomes challenging, making it difficult to apply model-based control methods in engineering practice. Aiming at the longitudinal control system of electric forklifts containing external disturbances, this paper proposes an improved full-format dynamic linearization model-free adaptive PID control (iFFDL-MFA-PID) method. Firstly, the full-format dynamic linearization (FFDL) method is employed to transform the operating system of the electric balanced forklift into a virtual equivalent linear data model. Secondly, the nonlinear residual term and pseudo-gradient (PG) of the data model are estimated using the difference estimation algorithm and the optimal criterion function, respectively. Furthermore, in order to enhance the robustness of the system, the idea of intelligent PID (iPID) is introduced and the principle of equivalent feedback is utilized to derive the iFFDL-MFA-PID control scheme. The design process of this scheme only requires the use of the input and output data of the system, without relying on the mathematical model of the system. Finally, the iFFDL-MFA-PID method proposed in this paper is simulated and tested with the EFG-BC/320 counterbalanced forklift equipped in the Special Equipment Testing Center and compared with the model-free adaptive control method (FFDL-MFAC) and the PID control method. Simulation results show that the speed-tracking error of the electric forklift truck under the action of the iFFDL-MFA-PID algorithm is maintained within ±0.132 m/s throughout the process, achieving higher tracking accuracy and better robustness compared to the MFAC and PID methods.

In order to enhance the performance of model-free adaptive control (MFAC) in solving the control problem caused by interference and improve the tracking speed, this paper focuses on the analysis and research of the system affected by interference using the MFAC method. This method is based on dynamic linearization technology, with system data which are represented by a full format dynamic linearization (FFDL) model that is very similar to actual industrial processes. In this work, a control law is derived by incorporating and assigning weights to both the output error and the output error rate (OER) as the performance index. Rigorous proofs are provided to establish convergence and stability. Considering the inherent complexity of actual systems, this paper also presents the MFAC-OER scheme for multiple-input–multiple-output (MIMO) systems. Furthermore, the effectiveness and practicality of the improved control strategy are evaluated through numerical arithmetic examples and control processes involving water level regulation in a circulating fluidized bed (CFB). Comparisons with conventional MFAC and PID control methods show that the enhanced control method is capable of quickly and accurately tracking the desired signal. Additionally, it exhibits superior anti-interference characteristics and is able to respond in a timely manner to changes in the operating conditions of the circulating fluidized bed system. As a result, it ensures the normal operation of the coal saver and water supply pipe without damage.

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

Fractures have significantly impacted the preservation, enrichment, and productivity of shale gas in the Longmaxi Formation in the complex structural area of the southern Sichuan Basin. Based on outcrop, core, imaging logging, inclusion analysis, acoustic emission experiments, and burial and thermal evolution history data, the formation stage, evolution and preservation conditions of structural fractures were comprehensively studied. Shear fractures are the main features of tectonic origin and are characterized by small widths, wide spacing, and high filling degrees. The structural fractures of the Longmaxi Formation can be divided into three groups in terms of their formation stage. The first-stage fractures were formed in the middle-late period of the Yanshanian tectonic movement (86.2–68.5 Ma), when the palaeotectonic stress was 68.33–71.82 MPa; and the homogenization temperature of the fluid inclusions in the corresponding fracture fillings is 150–178°C. The second-stage fractures were formed at the end of the Yanshanian -early Himalayan tectonic movement (68.5–35.2 Ma), when the palaeotectonic stress was 85.2–100.5 MPa; the homogenization temperature of the corresponding fluid inclusions is 123–148°C. The third-stage tectonic fractures formed during the middle-late period of the Himalayan tectonic movement (35.2–0 Ma), when the palaeotectonic stress was 55.6–63.8 MPa; fillings are scarce in these fractures, but the measured homogenization temperature of the corresponding fluid inclusions is 90–110°C. Shale gas preservation conditions were affected by the fracture formation stage, maximum horizontal crustal stress, fault scale, structural burial depth, formation pressure coefficient, etc. Three types of favourable preservation conditions were identified. The Type I target area is the low slope area in the middle of the syncline, which occurs more than 2.0 km from the fault. The research results have guiding significance for the evaluation of the preservation conditions of deep shale gas in the study area and similar areas.

For a more in-depth analysis on the marine chemical condition during the earliest Cambrian, mechanism of organic matter enrichment and exploration potential of shale gas resources, based on the petrology, organic geochemistry, and elemental characteristics of the W207 Well, this study discuss the Early Cambrian paleo-ocean environment and factors controlling of organic matter enrichment during the deposition of black strata Qiongzhusi Formation in the upslope areas, southwestern Sichuan Basin, Yangtze Block, China. The sedimentary cycles show that during the depositon of fine-grained Qiongzhusi Fm, interactive cycles of multiple deep-water and shallow-water shelf developed, and were controlled by the rise and fall in sea level. In particular, the slope turbidite (fan) and gravity flow sediments indicate that the shallow-water shelf facies were dominant in the upslope area (SW Sichuan Basin), where not in deep water for a long time, and the sedimentary thickness of the organic rich black shale was limited. Evidence from organic geochemistry indicates that the organic matter of the Qiongzhusi Fm from the W207 Well was mainly of type I kerogen, with a high degree of thermal evolution, little residual hydrocarbon, and low capacity for hydrocarbon generation. The redox parameters indicate that the marine environment on the upslope was medium restrictive, with some upwelling. The seawater had undergone a transformation according to anoxic–oxidic. Therefore, paleo-ocean productivity in the upslope area was generally low, and exhibited a prominent downward trend from bottom to top. Given its high risk of exploration, the authors suggest that the direction of shale gas resource evaluation should change to the intracratonic sag (downslope) area, which is characterized by deep-water shelf facies.

Abstract With the help of Aspen Plus, a two-dimensional unsteady CFD model is developed to simulate the coal gasification process in a fixed bed gasifier. A developed and validated two dimensional CFD model for coal gasification has been used to predict and assess the viability of the syngas generation from coal gasification employing the updraft fixed bed gasifier. The process rate model and the sub-model of gas generation are determined. The particle size variation and char burning during gasification are also taken into account. In order to verify the model and increase the understanding of gasification characteristics, a set of experiments and numerical comparisons have been carried out. The simulated results in the bed are used to predict the composition of syngas and the conversion of carbon. The model proposed in this paper is a promising tool for simulating the coal gasification process in a fixed bed gasifier.

Cognitive radio network is an intelligent wireless communication system which can adjust its transmission parameters according to the environment thanks to its learning ability. It is a feasible and promising direction to solve the spectrum scarcity issue and has become a research focus in communication community. However, cognitive radio network is vulnerable to jamming attack, resulting in serious degradation of spectrum utilization. In this article, we view the anti-jamming task of cognitive radio as a Markov decision process and propose an intelligent anti-jamming scheme based on deep reinforcement learning. We aim to learn a policy for users to maximize their rate of successful transmission. Specifically, we design Double Deep Q Network (Double DQN) to model the confrontation between the cognitive radio network and the jammer. The Q network is implemented using Transformer encoder to effectively estimate action-values from raw spectrum data. The simulation results indicate that our approach can effectively defend against several kinds of jamming attacks.

This paper focuses primarily on adaptive dynamic programming (ADP)-based tracking control of the hydraulic-driven flexible robotic manipulator system (HDFRMS) with varying payloads and uncertainties via singular perturbation theory (SPT). Firstly, the dynamics is derived using a driven Jacobin matrix, which represents the coupling between the hydraulic servo-driven system and rigid–flexible manipulator established using the assumed mode method and Lagrange principle. Furthermore, the whole dynamic model of the manipulator system is decoupled into a second slow subsystem (SSS), a second fast subsystem (SFS) and a first fast subsystem (FFS). The three subsystems can describe a large range of movement, flexible vibration and electro-hydraulic servo control, respectively. Hereafter, an adaptive dynamic programming trajectory tracking control law with a critic-only policy iteration algorithm is presented in the second slow timescale, while both robust optimal control (ROC) in the second first timescale and adaptive sliding mode control (ASMC) in the first fast timescale are also designed using the Lyapunov stability theory. Finally, the numerical simulations are carried out to illustrate the rightness and robustness of the singular perturbation decomposition and proposed composite control algorithm.

Adaptive control methods are suitable for offshore steel structures subject to harmful vibrations, as they employ reference models to adapt to coastal and nearshore physics. To decrease the dependence on the accurate characteristics of the offshore platform, a compensating measure containing the ocean environment is proposed in the adaptive control scheme. With incomplete states as the driving input, external loads are approximated using a wavelet neural network frame. Numerical experiments are conducted on a platform model with varying parameters to test the performance of the proposed adaptive controller. It is shown that the adaptive weights derived from the chosen Lyapunov function are qualified both theoretically and practically. The system-output-based adaptive controller overcomes the disadvantage of state loss. The compensated disturbance environment guarantees the reliability of the restored reference system based on mismatched physics. The designed estimator as a part of the adaptive controller compensates for the deviations of the environment between the reference and the practical, resulting in a desirable reduction in the excessive vibration.

Well interference has drawn great attention in the development of shale gas reservoirs. In the W shale gas reservoir, well interference increased from 27% to 63% between 2016 and 2019, but the gas production recovery of parent wells was only about 40% between 2018 and 2019. Therefore, the mechanism and influencing factor of well interference degree were analyzed in this study. A numerical model of the W shale gas reservoir was developed for history matching, and the mechanisms of well interference and production recovery were analyzed. Sensitivity analysis about the effect of different parameters on well interference was carried out. Furthermore, the feasibility and effectiveness of gas injection pressure boosting to prevent interference were demonstrated. The results show that the main causes of inter-well interference are: the reservoir energy of the parent well before hydraulic fractures of the child well, well spacing, the fracture connection, etc. The fracture could open under high pressure causing fracturing fluid to flow in, while fracture closure happens under low pressure and the influence on the two-phase seepage in the fracture becomes more serious. The combination of liquid phase retention and fracture closure comprehensively affects the gas phase flow capacity in fractures. Gas injection pressure boosting can effectively prevent fracturing fluids flowing through connected fractures. Before the child well hydraulic fracturing, gas injection and pressurization in the parent well could reduce the stress difference and decrease the degree of well interference. The field case indicates that gas channeling could be effectively prevented through parent well gas injection pressurization.

Abstract Background To clarify the effects of cylcin E1 expression on HCC tumor progression, we studied the expression of cyclin E1 and inhibitory efficacy of regorafenib and sorafenib in HCC cells, and investigated a potential therapy that combines regorafenib treatment with cyclin E1 inhibition. Methods Western blotting for caspase-3 and Hoechst 33225 staining was used to measure the expression level of apoptosis-related proteins under drug treatment. Results Our results showed that enhanced expression of cyclin E1 after transfection compromised apoptosis in HCC cells induced by regorafenib or sorafenib. Conversely, down-regulation of cyclin E1 gene expression or inhibition of cyclin E1 by the cyclin-dependent kinase (CDK) inhibitors dinaciclib (DIN) or flavopiridol sensitized HCC cells to regorafenib and sorafenib by inducing apoptosis. The expression of Mcl-1, which is modulated by STAT3, plays a key role in regulating the therapeutic effects of CDK inhibitors. Xenograft experiments conducted to test the efficacy of regorafenib combined with DIN showed dramatic tumor inhibitory effects due to induction of apoptosis. Our results suggested that the level of cyclin E1 expression in HCCs may be used as a pharmacodynamic biomarker to assess the antitumor effects of regorafenib or sorafenib. Conclusions Combining regorafenib and CDK inhibitors may enhance the clinical efficiency of the treatment of HCCs.

Abstract Background Scleractinian corals are important reef builders, but around the world they are under the threat of global climate change as well as local stressors. Molecular resources are critical for understanding a species’ stress responses and resilience to the changing environment, but such resources are unavailable for most scleractinian corals, especially those distributed in the South China Sea. We therefore aimed to provide transcriptome resources for 14 common species, including a few structure forming species, in the South China Sea. Description We sequenced the transcriptome of 14 species of scleractinian corals using high-throughput RNA-seq and conducted de novo assembly. For each species, we produced 7.4 to 12.0 gigabases of reads, and assembled them into 271 to 762 thousand contigs with a N50 value of 629 to 1427 bp. These contigs included 66 to 114 thousand unigenes with a predicted open reading frame, and 74.3 to 80.5% of the unigenes were functionally annotated. In the azooxanthelate species Tubastraea coccinea, 41.5% of the unigenes had at least a best-hit sequence from corals. In the other thirteen species, 20.2 to 48.9% of the annotated unigenes had best-hit sequences from corals, and 28.3 to 51.6% from symbiotic algae belonging to the family Symbiodinaceae. With these resources, we developed a transcriptome database (CoralTBase) which features online BLAST and keyword search for unigenes/functional terms through a user friendly Internet interface. Short conclusion We developed comprehensive transcriptome resources for 14 species of scleractinian corals and constructed a publicly accessible database (www.comp.hkbu.edu.hk/~db/CoralTBase). CoralTBase will facilitate not only functional studies using these corals to understand the molecular basis of stress responses and adaptation, but also comparative transcriptomic studies with other species of corals and more distantly related cnidarians.

Background/Aims: Previous studies have demonstrated that long non-coding RNAs (lncRNAs) may play critical roles in cancer biology, including Hepatocellular carcinoma (HCC). The HOXA cluster antisense RNA2 (HOXA-AS2) lncRNA plays an important role in carcinogenesis, however, the underlying role of HOXA-AS2 in HCC remains unknown. The present study examined the effects of HOXA-AS2 on the progression of HCC, and explored the underlying molecular mechanisms. Methods: Quantitative real-time PCR was used to detect HOXA-AS2 expression in HCC tissues and cell lines. Furthermore, the effects of HOXA-AS2 silencing and overexpression on cell proliferation, cell cycle, apoptosis, migration, and invasion were assessed in HCC in vitro and in vivo. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in HCC cells. Results: We observed that HOXA-AS2 was up-regulated in HCC tissues and cell lines. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited HCC cells proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell growth. Further functional assays indicated that HOXA-AS2 significantly promoted HCC cell migration and invasion by promoting EMT. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3’-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in HCC cells. MiR-520c-3p was down-regulated and inversely correlated with HOXA-AS2 expression in HCC tissues. miR-520c-3p suppressed cell proliferation, invasion and migration in HCC cells, and enforced expression of miR-520c-3p attenuated the oncogenic effects of HOXA-AS2 in HCC cells. By bioinformatic analysis and dual-luciferase reporter assay, we found that miR-223-3p directly targeted the 3’-untranslated region (UTR) of Glypican-3 (GPC3), one of the key players in HCC. GPC3 was up-regulated in HCC tissues, and was negatively correlated with miR-520c-3p expression and positively correlated with HOXA-AS2 expression. Conclusion: In summary, our results suggested that the HOXA-AS2/miR-520c-3p/GPC3 axis may play an important role in the regulation of PTC progression, which could serve as a biomarker and therapeutic target for HCC.

International deep seabed resource surveys have accumulated a large amount of valuable marine geochemical data. These data, however, derive from a number of autonomous heterogeneous information sources that show the characteristics of big data, i.e., multidisciplinary, multidimensional, multisemantic, and with strong correlations. The traditional database federation method is thus not applicable. To achieve marine geochemical data interoperation, an approach is proposed in this paper. The approach first builds a marine sample ontology (MSO) based on marine geochemical metadata standards. With support of the MSO ontology, which serves as a specification for the semantics and model of multisource heterogeneous data, the data integration and unified query APIs are accomplished across different databases. The experiment is applied with three databases: the ICP-AES database model in the ODP project, the PetDB marine petrology database model compiled at the Lamont-Doherty Earth Observatory, and the GEOROC database model operated by the German Max Planck Institute. The experimental results show that this method not only improves the efficiency of the marine geochemical data integration but also realizes the reuse of data and models under the premise of ensuring the independence, security, and timeliness of the data sources.

Coverage-based Greybox Fuzzing (CGF) is a practical and effective solution for finding bugs and vulnerabilities in software. A key challenge of CGF is how to select conducive seeds and allocate accurate energy. To address this problem, we propose a novel many-objective optimization solution, MooFuzz, which can identify different states of the seed pool and continuously gather different information about seeds to guide seed schedule and energy allocation. First, MooFuzz conducts risk marking in dangerous positions of the source code. Second, it can automatically update the collected information, including the path risk, the path frequency, and the mutation information. Next, MooFuzz classifies seed pool into three states and adopts different objectives to select seeds. Finally, we design an energy recovery mechanism to monitor energy usage in the fuzzing process and reduce energy consumption. We implement our fuzzing framework and evaluate it on seven real-world programs. The experimental results show that MooFuzz outperforms other state-of-the-art fuzzers, including AFL, AFLFast, FairFuzz, and PerfFuzz, in terms of path discovery and bug detection.

The Zonula Occludens proteins ZO-1 and ZO-2 are cell-cell junction-associated adaptor proteins that are essential for the structural and regulatory functions of tight junctions in epithelial cells and their absence leads to early embryonic lethality in mouse models. Here, we use the embryoid body, an in vitro peri-implantation mouse embryogenesis model, to elucidate and dissect the roles ZO-1 and ZO-2 play in epithelial morphogenesis and de novo tight junction assembly. Through the generation of individual or combined ZO-1 and ZO-2 null embryoid bodies, we show that their dual deletion prevents tight junction formation, resulting in the disorganization and compromised barrier function of embryoid body epithelial layers. The disorganization is associated with poor microvilli development, fragmented basement membrane deposition and impaired cavity formation, all of which are key epithelial tissue morphogenetic processes. Expression of Podocalyxin, which positively regulates the formation of microvilli and the apical membrane, is repressed in embryoid bodies lacking both ZO-1 and ZO-2 and this correlates with an aberrant submembranous localization of Ezrin. The null embryoid bodies thus give an insight into how the two ZO proteins influence early mouse embryogenesis and possible mechanisms underlying the embryonic lethal phenotype.

Blood filtration in the kidney glomerulus is essential for physiological homeostasis. The filtration apparatus of the kidney glomerulus is composed of three distinct components: the fenestrated endothelial cells, the glomerular basement membrane, and interdigitating foot processes of podocytes that form the slit diaphragm. Recent studies have demonstrated that podocytes play a crucial role in blood filtration and in the pathogenesis of proteinuria and glomerular sclerosis; however, the molecular mechanisms that organize the podocyte filtration barrier are not fully understood. In this study, we suggest that tight junction protein 1 (Tjp1 or ZO-1), which is encoded by Tjp1 gene, plays an essential role in establishing the podocyte filtration barrier. The podocyte-specific deletion of Tjp1 down-regulated the expression of podocyte membrane proteins, impaired the interdigitation of the foot processes and the formation of the slit diaphragm, resulting in glomerular dysfunction. We found the possibility that podocyte filtration barrier requires the integration of two independent units, the pre-existing epithelial junction components and the newly synthesized podocyte-specific components, at the final stage in glomerular morphogenesis, for which Tjp1 is indispensable. Together with previous findings that Tjp1 expression was decreased in glomerular diseases in human and animal models, our results indicate that the suppression of Tjp1 could directly aggravate glomerular disorders, highlights Tjp1 as a potential therapeutic target.

Phosphatase of regenerating liver 3 (PRL-3) is known to be overexpressed in many tumors, and its transcript level is high in the vasculature and endothelial cells of malignant tumor tissue. However, the mechanism(s) underlying its enhanced expression and its function in endothelial cells remain unknown. Here, we report that vascular endothelial growth factor (VEGF) can induce PRL-3 transcription in human umbilical vein endothelial cells (HUVEC). An analysis of its 5'UTR revealed that PRL-3 transcription is initiated from two distinct sites, which results in the formation of the two transcripts, PRL-3-iso1 and PRL-3-iso2, but only the latter is up-regulated in HUVEC by VEGF. The PRL-3-iso2 promoter region includes two functional MEF2 (myocyte enhancer factor2) binding sites. The over-expression of the constitutively active form of MEF2C promotes the abundance of the PRL-3-iso2 transcript in a number of human cell lines. The siRNA-induced knockdown of MEF2C abolished the stimulative effect of VEGF on PRL-3 transcript in HUVEC, indicating that the VEGF-induced promotion of PRL-3 expression requires the presence of MEF2C. Finally, blocking PRL-3 activity or expression suppresses tube formation by HUVEC. We suggest that PRL-3 functions downstream of the VEGF/MEF2C pathway in endothelial cells and may play an important role in tumor angiogenesis.