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Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

Silicate-modified polyurethane (PU/WG) is an effective organic–inorganic hybrid-grouting material that blocks water and reinforces weak formations. In deep high-temperature formations, owing to environmental impacts, PU/WG raw materials are heated before grouting. To elucidate the basic characteristics of PU/WG grouting materials in deep, high-temperature environments, we investigated the effects of raw material temperature on the curing time and strength of PU/WG by considering different mass ratios during the curing time test. Furthermore, the influence of raw material temperature on the micro-structure of PU/WG was analysed from a microscopic perspective using scanning electron microscopy. Energy-dispersive X-ray spectroscopy revealed the composition and curing mechanism of PU/WG. The results indicated that as the raw material temperature increased from 24 to 60°C, the peak strength decreased from 41.65 to 14.51 MPa, and the peak strain decreased from 27.03 % to 8.83 %. Based on the experimental results of the curing time testing and strength test, we established a PU/WG curing time-variation model considering the coupling of raw material temperature and mass ratio and provided an optimisation scheme for the PU/WG strength, which provides effective guidance for grouting time design in high-temperature environments.

Underground hydrogen storage (UHS) and compressed air energy storage (CAES) are two viable large-scale energy storage technologies for mitigating the intermittency of wind and solar power. Therefore, it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes. This study employs a multi-physical coupling model to compare the operations of CAES and UHS, integrating gas thermodynamics within caverns, thermal conduction, and mechanical deformation around rock caverns. Gas thermodynamic responses are validated using additional simulations and the field test data. Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes. Hydrogen reaches higher temperature and pressure following gas charging stage compared to air, and the ideal gas assumption may lead to overestimation of gas temperature and pressure. Unlike steel lining of CAES, the sealing layer (fibre-reinforced plastic FRP) in UHS is prone to deformation but can effectively mitigates stress in the sealing layer. In CAES, the first principal stress on the surface of the sealing layer and concrete lining is tensile stress, whereas UHS exhibits compressive stress in the same areas. Our present research can provide references for the selection of energy storage methods.

Karst cave causes geological disasters in tunneling engineering, which brings great risks to subway construction. The microtremor survey has become one of the main methods for karst cave detection in urban areas due to its convenience and great detection depth. However, the microtremor survey lacks high-frequency signals, resulting in poor detection accuracy on the shallow layer. An advanced method called mixed-source surface wave (MSW) method is proposed by imposing active sources during the continuous passive surface wave survey. MSW is applied to the detection of beaded karst caves (i.e. two or three karst caves at different depths in the same location) in Ji'nan, China. The influences of ambient noise, array type, and other factors on the detection accuracy were studied. Experimental results show that the detection depth and accuracy of MSW are much better than those of passive surface wave method. The inversion accuracy of linear array perpendicular to road is better than the triangle array and L-shaped array. The accuracy of the linear array along the road is worst. The detection accuracy of MSW is similar to that of combined active–passive surface wave methods. However, the basic principle of MSW is easier to understand, and its operation is more convenient. The two-dimensional measurement results show that the MSW method can well reflect the size and location of the beaded karst cave and provide important references for the practical engineering.

Abstract. Hepatitis B virus (HBV) represents the commonest etiologic agent of acute-on-chronic liver failure (ACLF) in most Asian countries. Nucleos(t)ide analogs (NAs) are effective in the treatment of chronic HBV infections, but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately. The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs (IMNA). A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015. Among these, 777 chronic hepatitis B (CHB) and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors, including IMNA, HBV reactivation (HBVR), infections, treatment drugs, alcohol use and others (hepatitis C virus, hepatitis E virus, gastrointestinal bleeding and unknown reasons). The percentage and improvement rate were examined. Among individuals with HBV-associated ACLF and CHB, IMNA was found in 9.01%, HBVR in 46.20%, infections in 9.52%, treatment drugs in 14.67%, alcohol in 11.71%, and others in 24.58% as predisposing factors. Improvement rates in cases with IMNA, HBVR, infections, treatment drugs, alcohol and others were 41.43%, 58.50%, 58.11%, 56.14%, 53.85%, and 65.97%, respectively. Multivariable analysis showed that IMNA, others, infections, hepatic encephalopathy and hepatorenal syndrome were associated with prognosis. Only IMNA independently predicted HBV-associated ACLF prognosis. Overall, our study demonstrated that the percentage of IMNA-induced HBV-associated ACLF was 12.61%, and worse disease conditions resulted from IMNA compared with other factors. Thus, the suitability of treatment with NAs should be thoroughly evaluated.

Various diseases and failures inevitably appear on expressway roadways in water-rich strata under the long-term erosion of water. It is very difficult to support the surrounding rock of a water-rich roadway because water will corrode the anchorage bond and weaken the surrounding rock mass. In the process of supporting, damage and fracture of anchor bolt often appear in water-rich roadway. In order to study the stability analysis of a support anchor bolt in the process of surrounding rock fracture evolution and the relationship between the prestressed value and the length of the anchor bolt, this paper studied the fracture evolution law of surrounding rock and the progressive debonding law of the bolt are studied by RFPA3D numerical simulation and used MATLAB software to calculate and draw several graphs to reveal the mechanism by analytical method. The following main conclusions were drawn: (1) the change and attenuation of the surrounding rock stress have a certain influence on the stability of the supporting bolt. The existence of confining pressure (horizontal stress) has a significant impact on the ultimate pullout force of anchor bolts. (2) With the gradual destruction of the surrounding rock, the shear stress, horizontal stress, and vertical stress in the surrounding rock are gradually reduced to zero, and the change speed of the surrounding rock is fast at the shallow surface and slow at the deep. (3) The interface shear stress tends to a low stable value after debonding, which means the value of friction resistance is relatively stable in different positions. (4) The frictional resistance after interface debonding is an important condition to maintain the balance of higher anchorage force. If there is no friction resistance, when the axial force of the anchor bolt reaches the initial critical value, the interface debunking process will develop catastrophically and cannot be stabilized until complete failure, even if the axial force no longer increases.

The slurry–earth pressure balance dual-mode shield has an earth pressure balance (EPB) and slurry shield functions. Based on a shield tunnel project of Guangzhou Metro Line 12 in China, this study investigates the clogging prevention of a slurry–earth pressure balance dual-mode shield in a composed stratum with medium–coarse sand and argillaceous siltstone. The results show that the slurry mode was not applicable to the composed stratum with medium–coarse sand and argillaceous siltstone. The excavated soil accumulated easily in the slurry chamber, causing shield clogging. The total thrust force of the shield increased significantly, the tunneling speed gradually decreased to 0, and the torque of the cutterhead increased slightly after the slurry shield was clogged. The fluctuation in the total thrust force, the cutterhead torque, and the tunneling speed also increased significantly. The EPB mode is recommended for composed strata with medium–coarse sand and argillaceous siltstone. The dispersible foam agent and water needed to be used for soil conditioning. The injection amount of foam and water was determined according to the status of the mud discharged by the screw conveyor. Water absorption can be used to characterize the water absorption capacity of particles larger than 0.15 mm. The ideal soil state was that the consistency index of the particles smaller than 0.15 mm was less than 0.5 to prevent the EPB shield from clogging. The water absorption of soil with a particle larger than 0.15 mm should be removed when calculating the consistency index.

When a slurry shield tunnel boring machine (TBM) encounters sticky ground during tunneling, mud cakes often occur on the cutter head due to the high stickiness of soil. The mud cakes caused several negative issues, such as high torque demand, advancement rate reduction, and additional costs. Existing studies have largely focused on Earth pressure balance TBMs; research on formation and mitigation measures of mud cakes in slurry shield TBMs is limited. Therefore, this study proposes the addition of dispersant to the slurry to prevent mud cakes during the tunneling of slurry shield TBMs by reducing stickiness of excavated clay. The basic properties of slurry were measured experimentally, and the effectiveness of dispersant in reducing the potential for mud cakes was investigated through mixing tests and viscosity experiments. A statistical analysis of the data was performed to determine relationships between slurry properties and material behaviors. The results showed that the slurry with dispersant had a lower viscosity and formed filter cakes more quickly, thereby meeting the performance requirements of a supporting fluid for slurry shield TBMs. Further, dispersant effectively reduced the empirical stickiness ratio and suspension viscosity. Therefore, a slurry with an appropriate dispersant content could effectively reduce the potential for mud cake formation.

Many numerical methods are carried out to study the nonlinear failure behaviors of the rock; however, the numerical simulation methods for the failed rock are still in the research stage. This paper establishes the damage constitutive equation by combining the bilinear strain softening constitutive model with energy dissipation principles, as well as the energy failure criterion of mesoscopic elements based on the strain energy density theory. When the strain energy stored by an element exceeds a fixed value, the element enters the damage state and the damage degree increases with increasing energy dissipation. Simultaneously, the material properties of the damaged element change until it becomes an element with certain residual strength. As the load increases, the damage degree of an element increases. When the strain energy stored by an element exceeds the established value of the energy criterion, the element is defined to be failed. As the number of failed elements constantly increases, failed elements interconnect and form macrocracks. The rock fracture calculation program on the basis of the preceding algorithm is successfully applied to the fracture simulation process in Brazilian splitting, tensile tests with build-in crack and tunnel excavation.

The harmonious development of urban rail transit, underground space engineering, and social economy is the key to regional sustainable development. Based on synergetic theory, this paper constructs the coupling coordination evaluation system of “rail transport-social economy” composite system at the scale of a city cluster. With this system, the coupling and coordinated development pattern and characteristics of “rail transit-social economy” in the Yangtze River Delta city cluster from 2002 to 2020 were analyzed. The paper makes a horizontal comparison with the Beijing-Tianjin-Hebei city cluster and the Pearl River Delta city cluster, as well as analyzes the differences in development and existing problems, and puts forward policy suggestions for rail and urban underground space development. The results show that: (1) The rail transit of 11 cities in the Yangtze River Delta shows a “step by step” development pattern. That is “national central city, provincial city, second-tier city, third-tier city, etc.”, accompanied by periodic changes of coupling and coordination degree. In addition, there is also the phenomenon of unbalanced development within the region; (2) From 2002 to 2020, the development of rail transit in the three city clusters shows a situation of “the overall supply is lacking and lags behind the social economy for a long time”. Among them, the Pearl River Delta city cluster has the most serious lags. Multi-channel financing, speeding up the construction of the rail transit scale according to local conditions, and improving operating efficiency are considered to be the keys to solve this problem; (3) In general, the coupling between rail transit and the social economy in the Yangtze River Delta city cluster is better than that in the Beijing-Tianjin-Hebei city cluster and the Pearl River Delta city cluster, but the coordination is at a slight disadvantage.

With the rapid growth of scientific publications, research paper recommendation which suggests relevant research papers to users can bring great benefits to researchers. In this paper, we focus on the problem of recommending conference papers to the conference attendees. While most of the related existing methods depend on the content-based filtering, we propose a unified conference paper recommendation method named $CPRec$ , which exploits both the contents and the authorship information of the papers. In particular, besides the contents, we exploit the relationships between a user and the authors of a paper for recommendation. In our method, we extract several features for a user-paper pair from the citation network, the coauthor network, and the contents, respectively. In addition, we derive a user’s pairwise preference towards the conference papers from the user’s bookmarked papers in each conference. Furthermore, we employ a pairwise learning to rank model which exploits the pairwise user preference to learn a function that predicts a user’s preference towards a paper based on the extracted features. We conduct a recommendation performance evaluation using real-world data and the experimental results demonstrate the effectiveness of our proposed method.

Shotcrete is an essential preliminary support means in New Austrian Tunneling Method (NATM) construction and plays a very important role in controlling the stability of surrounding rock. The accelerator is a necessary admixture in shotcrete and its quality can greatly affect shotcrete performance. This paper proposes a new liquid accelerator characterized by short initial and final setting time, small dosage, and good adaptability to cement. Laboratory tests and field tests are conducted to verify the influence of this liquid accelerator on performance of shotcrete. Numerical simulation is carried out to study the strength growth of shotcrete with time and interaction between the strength and stress release of surrounding rock. The results show that the initial and final setting time of this liquid accelerator is 2 minutes and 4 minutes respectively. Its dosage is just 1.5% to 4% of the cement quantity. Adding this liquid accelerator can effectively improve the early strength and reduce the later strength loss of shotcrete, and therefore enhance the supporting effects of shotcrete on surrounding rock. In the field application, it is an ideal liquid accelerator for shotcrete, characterized by little resilience, no slurry shedding, and low dust.

Many numerical methods are carried out to study the nonlinear failure behaviors of the rock; however, the numerical simulation methods for the failed rock are still in the research stage. This paper establishes the damage constitutive equation by combining the bilinear strain softening constitutive model with energy dissipation principles, as well as the energy failure criterion of mesoscopic elements based on the strain energy density theory. When the strain energy stored by an element exceeds a fixed value, the element enters the damage state and the damage degree increases with increasing energy dissipation. Simultaneously, the material properties of the damaged element change until it becomes an element with certain residual strength. As the load increases, the damage degree of an element increases. When the strain energy stored by an element exceeds the established value of the energy criterion, the element is defined to be failed. As the number of failed elements constantly increases, failed elements interconnect and form macrocracks. The rock fracture calculation program on the basis of the preceding algorithm is successfully applied to the fracture simulation process in Brazilian splitting and intermediate crack tensile tests.

Al has significant effect on properties of minerals. We reported crystal structure and elasticity of phase H, an important potential water reservoir in the mantle, which contains different Al using first principles simulations for understanding the effect of Al on the phase H. The crystal and elastic properties of Al end-member phase H (Al2O4H2) are very different from Mg end-member (MgSiO4H2) phase H and two aluminous phase H (Mg0.875Si0.875Al0.25O4H2 (12.5at%Al) and Mg0.75Si0.75Al0.5O4H2 (25at% Al)). However differences between Mg end-member phase H and aluminous phase H are slight except for the O-H bond length and octahedron volume. Al located at different crystal positions (original Mg or Si position) of aluminous phase H has different AlO6 octahedral volumes. For three Al-bearing phase H, bulk modulus (K), shear modulus (G), compressional wave velocity (Vp) and shear wave velocity (Vs) increase with increasing Al content. Under high pressure, density of phase H increases with increasing Al content. The Al content affects the symmetry of the phase H and then affects the density and elastic constants of phase H. The total ground energy of phase H also increases with increasing Al content. So an energy barrier for the formation of solid solution of phase H with δ-phase AlOOH is expected. However, if the phase H with δ-phase AlOOH solid solution does exit in the mantle, it may become an important component of the mantle or leads to a low velocity layer at the mantle.

The U-shaped girder is a type of open thin-walled structure, which is used in urban rail transit engineering. Although it employs polypropylene fiber concrete to avoid cracks, the girder is still easier to crack than other traditional structures owing to its special open thin-walled cross section. In this study, a cracking accident of a U-shaped girder, which happened during the prestressed steel tensioning, was studied by field investigation and mechanical analysis through the finite element (FE) method. An outline of the cracks was presented. The nonlinear material properties of the polypropylene fiber concrete and steel were discussed and used in the finite element model. The effects of the main design parameters, such as the flange slab thickness, anchorage position, and prestressed steel layout, were evaluated based on the results of the FE analysis. The results indicate that the extremely low rigidity of the web and oversize of the web longitudinal prestressed steels are the main reasons for the cracks. The risk of cracks can be reduced by increasing the thickness of the flange slab and changing the anchorage position and prestressed steel layout. Some suggestions are provided for avoiding cracks based on the results of the research.