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The existence of related faults between components brings great difficulties to the analysis of the importance of system components. How to quantify the influence of related faults and evaluate the importance of components is one of the hot issues in current research. In this paper, under the assumption that the fault propagation obeys the Markov process, the PageRank algorithm is integrated into the decision-making trial and evaluation laboratory (DEMATEL). On the basis, the calculation of influencing degree and influenced degree between components is studied to quantify the influence of related faults, and the problem of subjective evaluation of weight coefficient in traditional DEMATEL is solved. The rationality is verified through the method of combining the Interpretative Structural Modeling Method (ISM) and direct relation matrix. The importance of system related faults is identified accurately based on the calculation of center degree and cause degree, and the central-related faults of CNC machine tools are analyzed as an example to verify the effectiveness of the proposed method.

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a crucial role in the Toll-like receptor/IL-1R signal pathway, which mediates the downstream signal transduction involved in innate and adaptive immunity. In the present study, an IRAK4 homologue (named as MaIRAK4) from blunt snout bream (Megalobrama amblycephala) was cloned and characterized. The open reading frame (ORF) of MaIRAK4 contains 1422 nucleotides, encoding a putative protein of 473 amino acids. Protein structural analysis revealed that MaIRAK4 has an N-terminal death domain (DD) and a central kinase domain (S_TKc), similar to those of mammals and other fishes. Multiple sequence alignment demonstrated that MaIRAK4 is highly homologous with that of grass carp (97.67%). The qRT-PCR analysis showed that MaIRAK4 expressed widely in all examined tissues, including heart, liver, spleen, kidney, head-kidney, gill, intestine and muscle, with the highest expression in the liver and spleen. After stimulation with LPS, MaIRAK4 expression upregulated significantly and reached a peak at 6 h and 12 h post LPS stimulation in the spleen and head-kidney, respectively. After challenge with Aeromonas hydrophila, MaIRAK4 expression peaked at 48 h and 72 h in spleen/head-kidney and liver, respectively. These results implied that MaIRAK4 is involved in the host defense against bacterial infection. Subcellular localization analysis indicated that MaIRAK4 distributed in the cytoplasm. Co-immunoprecipitation and subcellular co-localization assay revealed that MaIRAK4 can combine with MaMyD88 through DD domain. MaIRAK4 overexpression can induce slightly the NF-κB promoter activity in HEK 293 cells. However, the activity of NF-κB promoter was dramatically enhanced after co-transfection with MaIRAK4 and MaMyD88 plasmids. The results showed that MaIRAK4 was involved in NF-κB signal pathway mediated by maMyD88. The expression level of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) decreased significantly after the siRNA-mediated knockdown of MaIRAK4. Together, these results suggest that MaIRAK4 plays an important function in the innate immunity of M. amblycephala by inducing cytokines expression.

Background The evidence of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitor and immune checkpoint inhibitor in unresectable hepatocellular carcinoma (HCC) was limited. This study aimed to evaluate the role of TACE plus apatinib (TACE + A) and TACE combined with apatinib plus camrelizumab (TACE + AC) in patients with unresectable HCC. Methods This study retrospectively reviewed patients with unresectable HCC who received TACE + A or TACE + AC in 20 centers of China from January 1, 2019 to June 31, 2021. Propensity score matching (PSM) at 1:1 was performed to reduce bias. Treatment-related adverse events (TRAEs), overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were collected. Results A total of 960 eligible patients with HCC were included in the final analysis. After PSM, there were 449 patients in each group, and the baseline characteristics were balanced between two groups. At data cutoff, the median follow-up time was 16.3 (range: 11.9–21.4) months. After PSM, the TACE + AC group showed longer median OS (24.5 vs 18.0 months, p Conclusions Both TACE plus apatinib and TACE combined with apatinib plus camrelizumab were feasible in patients with unresectable HCC, with manageable safety profiles. Moreover, TACE combined with apatinib plus camrelizumab showed additional benefit.

Transforming growth factor-β activated kinase-1 (TAK1) is an important upstream signaling molecules involved in the NF-κB signaling pathway. TAK1 interacts with TAB1 to form the TAK1-TAB1 complex, which elicits NF-κB activation through a series of cascade reactions in mammals. However, the function of TAK1 in blunt snout bream (Megalobrama amblycephala ( maTak1) and the effects of their interaction between TAK1 and TAB1 on the NF-κB activation still remains largely unknown. In the present study, maTak1 was cloned and characterized successfully based on transcriptome data. Its open reading frame is composed of 1626 nucleotides and the predicted maTAK1 protein contains 541 amino acids, which includes an N-terminal Serine/Threonine protein kinases (S/TKc) and a C-terminal coiled-coil region. Phylogenetic analysis showed that maTAK1 were clustered with those of other teleosts. MaTak1 displayed ubiquitous transcriptional expression in all the examined tissues of healthy blunt snout bream but with varied expression levels. And maTrak1 expression was dramatically enhanced in different tissues and MAF cells after LPS stimulation and A. hydrophila challenge. The result from subcellular localization analysis indicated that both maTAK1 and maTAB1 were cytoplasmic protein. The activity of NF-κB promoter could not be induced by overexpression of maTak1 or maTab1 alone, however, it could be enhanced by co-expression of maTak1 and maTab1. Co-immunoprecipitation and subcellular co-localization assay revealed that maTAK1 can combine with maTAB1 directly. The transcriptional expression level of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8) increased distinctly after the overexpression of maTak1 and maTab1. Taken together, the data obtained in this study demonstrated that the direct interaction between maTAK1 and maTAB1 might play a pivotal role in mediating host innate immune response to pathogen invasion by the production of pro-inflammatory cytokines via NF-κB signaling pathway, which might lay a solid foundation for the establishment of novel therapeutic approach to combat bacterial infection in fish.

Toll-interacting protein (Tollip) is an important negative regulator of Toll-like receptor-mediated innate immunity by preventing excessive proinflammatory responses. The structure and function of Tollip have been well identified in mammals, but the piscine Tollip remains poorly understood. In the present study, a homologue of Tollip was identified and characterized from blunt snout bream (named MaTollip), which was composed of an 831 bp open reading frame encoding a protein of 276 amino acids. Phylogenetic analysis indicated that MaTollip is a novel member of Tollip family and possessed the highest similarity to that of grass carp (99.28%). Multiple alignment of amino acid sequence showed that MaTOLLIP shared a high degree of structural conservation, including a TBD domain, a C2 domain and a CUE domain, with its counterparts from other vertebrates. With regard to tissue-specific expression without immune challenge, MaTollip was constitutively expressed in a wide range of normal tissues, with the highest in the head-kidney and the lowest in the intestine. MaTollip expression in the head-kidney was strongly upregulated upon LPS stimulation and A. hydrophila infection. Fluorescence microscopic analysis revealed that the green fluorescent protein-TOLLIP was localized predominantly in the cytoplasm of EPC cells in a dot-like state. When MaTollip was overexpressed in HEK-293T and EPC cells, it could significantly inhibit the activity of nuclear factor-κB (NF-κB) promoter in a dose dependent manner. MaTollip overexpression in MAF cells lowered drastically the transcriptional expression level of lipopolysaccharide-induced proinflammatory cytokines (IL-1β, IL-6 and IL-8), whereas they were dramatically promoted by MaTollip knock down with siRNA. Taken together, this study demonstrated that MaTollip played a pivotal role in mediating host innate immune response to pathogen invasion, and unveiled the involvement of MaTollip in NF-κB-mediated transcription of inflammation genes, which paved the way for further studies of immune negative regulation mechanisms mediated by Tollip in fish.

Study on morphological changes of a bay can help to identify the effects of anthropogenic activities on coastal environment and guide the exploration of marine resources. In this paper, morphological data including coastline and water areas in five discrete years between 1968 and 2015 were selected and extracted from the remote sensing images and historical marine charts to study the morphological changes in Laizhou Bay (LZB), one of the bays in the southwest of the Bohai Sea. A systematic analysis on spatial variations of the coastline and the surface areas of different types of waters in LZB was conducted. The results showed that the surface area of LZB was decreased by 1253.2km2 in the last half century, which is 17.4% of the total in the 1970s. The areas of the natural wetland and the intertidal zone were decreased by 17.2% and 56.1%, respectively, and the average water depth varied from 9.05m to 8.16 m at low tide level from 1968 to 2015. The coastline and shape variations of the bay turned to be complex after the 1980s, and the shape index of LZB showed an increasing trend in more recent years. The centroid of the bay generally migrated to the northeast direction, i.e., the direction of the center of the Bohai Sea, and the shrinking direction of the bay was consistent with the migration direction of the coastline. The reclamation area during 1968–2015 in LZB was 1201.7 km2, and 94.1% was in the inter-tidal zone. The overall morphological change of the bay during the last half century was mainly controlled by the coastal reclamation activities, and the Yellow River runoff including the river course change and sediment load variation was also an important controlling factor.

Most traditional agricultural machines use traditional mechanical transmission with fuel drive and front wheel steering, and most of them are manned, with low transmission efficiency, poor flexibility and low level of intelligence. This paper proposes a new high ground clearance sprayer with four-wheel independent drive (4WID) with dual front and rear steering axles. This sprayer is an oil-electric hybrid that not only saves energy, but also reduces the pollution to crops. In this study, a path tracking controller and a self-correcting controller are constructed based on the kinematic model of the sprayer, respectively. The model prediction controller is used as the main controller, and it outputs the desired steering angle and speed of the sprayer based on the current state of the sprayer and the desired path to achieve path tracking control. The self-correcting controller, as an auxiliary controller, adopts fuzzy control method and designs fuzzy control rules based on the driver’s experience to correct the wheel turning angle at the current moment, which not only retains the advantages of model prediction control in linear path tracking, but also improves the control effect in curved path tracking and enhances the path tracking accuracy in large curvature roads. The simulation shows that the maximum lateral deviation of 0.03 m can be achieved by the model predictive control alone, and the maximum lateral deviation is reduced to 0.0141 m after adding the self-correcting controller.

Fractured vuggy carbonate reservoirs consist of matrix, fractures, and vugs. The existence of vugs in fractured vuggy carbonate reservoirs has long been observed. The volume of a vug is an important parameter owing to the large contribution of vugs to oil reserves. However, there are no reliable well test methods to estimate the volume of a vug yet. In this study, a new analytical well test model considering the coupling between oil flow and wave propagation is proposed. First, the mathematical model is established. Then, combined with the seepage equations in the outer formation, the analytical solutions of transient pressure in the wellbore are obtained through Laplace transformation and inversion. Second, based on the above analytical solutions, the standard log-log type curves are plotted to recognize the flow characteristics. It was found that, the flow in the wellbore and large vug can be divided into six distinct flow regimes. The volume of the large vug can be obtained by pressure transient analysis. Considering the coupling between oil flow and wave propagation, there will be one more V-shaped segment than typical triple-continuum pressure derivative curve. Third, a comparison with the triple-continuum model is performed to verify the validity and reliability of the proposed model in this study as well as a reservoir study. Finally, sensitivity analysis of some key parameters on the pressure derivative are carried out. Through the sensitivity analysis of different parameters for the well test type curves, it is found that the change in these well test curves is in accordance with the findings of the theoretical analysis. The curve behaviors are influenced by the friction coefficient, fluctuation coefficient, damping coefficient, storage ratios, and inter-porosity flow coefficients. The depth of the first V-shape segment is mainly affected by the friction, fluctuation, and damping coefficients. The depths and locations of the second and third V-shape segments are mainly influenced by the storage ratios of the fracture and vug, and inter-porosity flow coefficients within the matrix, fracture, and vug.

The fault-karst carbonate reservoirs in Tarim Basin have previously been determined to have promising prospects for exploration and development. Large karst caves are the main storage space and flow channel, which are separated from one another, yet connected by fractures. During the drilling processes, when large karst caves are encountered, drilling break and mud leakage often occur. Such occurrences make it impractical to carry out normal logging operations or determine the depths of the reservoirs. Therefore, in order to address the difficulties in determining the reservoir depths during the development fault-karst reservoirs, this study presented a method by which to accurately predict reservoir depths by means of combining the relationships between the flow temperatures and rest temperatures within the well structures. A mathematical model describing the heat transfer was established for the purpose of obtaining the temperature distributions of the fluid within the karst caves and wellbores during stable oil production, and the model was verified using numerical simulations. In addition, a temperature distribution method was applied to the temperature predictions of wells in Shunbei Block of Tarim Basin, and the reservoir depths were predicted at the same time. Then, the research results were compared with the seismic section of the fault-karst. It was found that good application effects and consistency had been achieved.

The bead-on-a-string structure has been widely observed in many fractured vuggy carbonate reservoirs, especially in Shunbei oilfield, northwestern China. To date, there are still no appropriate well test methods for analyzing these reservoirs with the vertical bead-on-a-string structure. This paper proposes a new theoretical well test model, which considers the gravity effect and the natural fractures connecting the vuggs, to analyze this kind of reservoirs. First, we establish the mathematical model of fractured vuggy reservoirs with the vertical bead-on-a-string structure. With the different outer boundary conditions, Laplace transform and inversion are employed to solve the well test model. Then, the type curves for the well test model are plotted and discussed. It is found that the gravity effect can be equivalent to a type of constant pressure boundary condition. Take the three-region-two-cave as an example, type curves can be divided into nine distinct flow regimes, including wellbore storage, skin, linear flow I and II, transition flow I and II, vug storage I and II, and boundary flow. The transition flow and vug storage period are named as the vug storage effect. Subsequently, the effects of relevant parameters are studied. It is concluded that the depth of the drop during vug storage effect increases with increasing dimensionless vug storage constant CvD and dimensionless vug height zD2-zD1; the greater dimensionless gravity effect coefficient GD leads to the smaller equivalent boundary distance of the constant pressure boundary condition; the smaller the mobility ratio M12, the earlier the appearance of the second linear flow regime; the larger the storage ratio ω 12, the more distinct the vug storage effect. Finally, two field case studies are carried out by using the proposed method. The locations and volumes of the caves are estimated, which shows that the proposed theoretical well test model has a great potential of obtaining the formation and cave parameters accurately. However, there is not available data that enable an accurate description of the locations and volumes of the caves by now, the proposed model still needs further field verifications.

Wu, Y.; Li, Q.; Liu, Y.; Xu, Y.; Wang, X., and Li, W., 2020. Study on dispersion of marine pollutants from islands in the southern section of Bohai Strait. In: Zheng, C.W.; Wang, Q.; Zhan, C., and Yang, S.B. (eds.), Air-Sea Interaction and Coastal Environments of the Maritime and Polar Silk Roads. Journal of Coastal Research, Special Issue No. 99, pp. 242–249. Coconut Creek (Florida), ISSN 0749-0208.The three-dimensional hydrodynamic model was established based on FVCOM, coupled with the Lagrangian particle tracking module to study the water exchange ability of 15 drain outlets of North and South Changshan Island. Meanwhile, the 30-day influence distance was introduced to quantify the water exchange ability. The drain outlets with a strong water exchange capacity are mainly located in the east of North and South Changshan Islands and the southwest corner of South Changshan Island, and those with a weak water exchange capacity are mainly located in the northwest corner of North Changshan Island, joint of South Changshan Island and the tombolo dyke and inside the Changdao Harbor. The 30-day influence range of the 15 drain outlets of North and South Changshan Islands is significantly affected by monsoon. East Asian monsoon accelerates the dispersion of the pollutants in the south sea areas of Bohai Strait.

Shunbei block is nearly the deepest oilfield in China with formation buried about 8000 meters. Good production performance is gained with rate as high as 100t/d per well. The formation belongs to fault-karst carbonates and is composed by caves, natural fractures and matrix. The current well testing models that assume dual or triple mediums cannot give reasonable interpretation such as the volume of caves and the connectivity between caves. We proposed a new model for the well connected to one cave in the carbonate formation based on the three laws of mass conservation, momentum conservation and energy conservation mechanics. The concept of wave propagation is introduced and the model incorporating fluid flow and pressure wave propagation is built in the caves. For the cave connected to the wellbore, its volume can be obtained by history match of the log-log plot of the pressure and pressure derivative. The matrix is viewed as storage medium and it provides fluid to the caves by crossflow. Field cases are conducted to validate the proposed method. Results show that the sequent flow regimes including wellbore storage, transition from wellbore storage to cave storage, wave propagation and fluid flow in cave, formation flow can be diagnosed in the log-log plot of the pressure and pressure derivative, therefore, the new method can characterize the features of fault-karst carbonate reservoirs such as the volume of caves. For the field case, from pressure buildup test, the volume of the caves connected to the wellbore is estimated as 37281.41 m3. Log-log plots of the pressure and pressure derivative show good agreement with the pressure buildup data, therefore, the models are validated and the results interpreted are accurate and confident.

Stereochemical determination of a new and cytotoxic euphane triterpenoid from the plant endophytic fungus Phomopsis chimonanthi