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The long-term action of internal and external factors leads constantly to seepage failures of soil levee engineering such as soil flow failure and piping failure. It is very disadvantageous to the service safety of levee engineering. Most of disastrous accidents are induced directly or indirectly by seepage. It has been known that the water–soil interaction with particle migration determines the occurrence and development of seepage failure. In this paper, a particle flow code (PFC)-based approach is introduced to implement the numerical simulation for seepage behavior in soil levee and investigate the meso-scale seepage failures. Firstly, according to the granular properties and particle migration characteristics of soil levee, an implementation process is presented to construct the meso-scale soil particle model and analyze the levee failure. Then, considering the coupling action of soil and water, a numerical method combining PFC with computation fluid dynamics is developed to simulate the seepage failure of soil levee. The corresponding criteria on seepage failures of soil levee are given. Lastly, one actual levee engineering is taken as an example. The movements of soil and water in the soil flow and piping processes are investigated with meso-scale soil particle model of selected levee. The meso-scale mechanism of seepage failures is analyzed, and the seepage stability is evaluated. It is indicated that the proposed PFC-based approach can fulfill the real-time observation for the movement status of soil particles and water during seepage failure of soil levee. The seepage stability identification with the introduced meso-scale criteria shows good agreement with the experimental result.

With the deepening of the reform of the electric power system and the continuous improvement of the demand level of electric power users, the psychological expectations of the market subjects have also undergone profound changes, and it is necessary to gradually strengthen and expand the key indicators and analysis dimensions that can reflect the operation situation of the electric power market, so as to adapt to the existing statistical analysis business needs. According to the current business content and demand of electricity market, this paper establishes a scientific and comprehensive evaluation index system of electricity market from the perspectives of market supply and demand, market structure, market behavior and market discipline. The system can reflect the development of power market comprehensively and objectively.

The existence of cracks is a key factor affecting the strength of concrete. However, traditional numerical methods still have some limitations in the simulation of crack growth in fissured concrete structures. Based on this background, the numerical treatment method of particle failure in smoothed particle hydrodynamics (SPH) is proposed, and the generation method for concrete meso-structures under the smoothed particle hydrodynamics (SPH) framework is developed. The concrete meso-models under different pre-existing micro-fissure inclinations and bridge angles (the inner tip line of the double pre-existing micro-fissure is defined as a bridge, and the angle between the bridge and the horizontal direction is defined as the bridge angle) were established, and numerical simulations of the crack propagation processes of concrete structures under tensile stress were carried out. The main findings were as follows: The concrete meso-structures and the pre-existing micro-fissures all have great impacts on the final failure modes of concrete. The stress–strain curve of the concrete model presents four typical stages. Finally, the crack initiation and propagation mechanisms of fissured concrete are discussed, and the application of smoothed particle hydrodynamics (SPH) in crack simulations of fissured concrete is prospected.

Cracks in rock and concrete have a great adverse effect on the stability of engineering structures; however, there are few studies on X-shaped fissures which widely exist in rock and concrete structures. Based on this background, three-point bending fracture tests of SCB specimens containing X-shaped fissures are carried out. The momentum equations in the SPH method are improved, and the crack propagations of SCB specimens under three-point bending are simulated. The results show that cracks grow simply along the vertical direction in the sample with no X-shaped fissures, and the existence of an X-shaped fissure changes the crack growth path and final failure modes of the SCB samples. The crack propagation simulation results are consistent with the experimental results, which verifies the rationality of the improved SPH method. The load–displacement curves mainly present three typical stages: the initial compaction stage, linear elastic deformation stage, and failure stage. The peak load decreases first then increases with an increase in eccentricity. With an increase in X-shaped fissure length and decrease in X-shaped fissure angle, the peak load decreases. The damage counts remain at 0 at the initial loading stage, corresponding to the initial compaction stage and the linear elastic deformation stage, and increase sharply at the later loading stage, corresponding to the failure stage, which is consistent with the experimental results. The influence mechanisms of X-shaped fissures on the crack propagation paths are discussed; the existence of different X-shaped fissure morphologies aggravate the tensile stress concentration at specific positions, leading to different crack propagation modes in the experiments. The research results can provide a certain reference for understanding the failure mechanisms of engineering structures containing X-shaped fissures and promote the applications of the SPH method into the simulations of cross-fissure crack propagations.

Taurolidine (TRD) is a substance derived from the amino sulfonic acid taurine, which was originally used to treat peritonitis and catheter-associated bloodstream infections, due to its antimicrobial and anti-inflammatory properties. A recent study reported the anticancer function of TRD in malignant tumors; however, the effects and mechanisms of TRD in liver cancer remain unclear. The present study aimed to investigate the effects and mechanism of TRD treatment on human liver cancer cells. The viability and apoptosis of liver cancer cells were evaluated using the MTT assay and flow cytometry. Subsequently, small interfering RNA (siRNA) was used to knock down the expression of gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), after which, reverse transcription-quantitative polymerase chain reaction was used to detect the mRNA expression levels of GRIM-19, whereas immunofluorescence was used to analyze the location of GRIM-19. Furthermore, western blotting was performed to detect the protein expression levels of GRIM-19, cyclin D1, signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)-STAT3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). The STAT3 pathway was inhibited using niclosamide. The results revealed that TRD reduced the viability of liver cancer cells and induced apoptosis at higher frequencies. In addition, the expression levels of GRIM-19 were increased in a time- and dose-dependent manner following TRD treatment. Alongside GRIM-19 upregulation, the expression levels of Bax were increased, whereas those of cyclin D1, Bcl-2 and p-STAT3 were decreased. Furthermore, following GRIM-19 knockdown, the effects of TRD on the viability and apoptosis of HepG2 cells, and the expression of downstream target genes (including cyclin D1, STAT3, p-STAT3, Bcl-2 and Bax) were reversed. Conversely, treatment with a p-STAT3 inhibitor had an inverse effect on the expression of these genes but did not affect GRIM-19 expression compared with the TRD group. These results indicated that TRD may contribute to cell apoptosis by inducing GRIM-19 expression and deactivating the STAT3 signaling pathway in liver cancer cells.

Risk calculation of levee in the complex environment has significant theoretical values and practical meanings. As there still exists problems in present risk calculation models, a simple and efficient calculation model of the comprehensive levee risk is needed to be established. This paper studies the comprehensive risk calculation model of levee with multiple failure modes based on the analysis of levee instability and seepage failure. Firstly, coupling calculation of the seepage field and stress field is made using the finite element method, and safety factor of levee slope and critical failure hydraulic gradient of levee foundation are determined according to the strength reduction and piping theory. Then, particle swarm optimization is applied to conduct a comparative study on potential impact factors of levee stability and seepage, thus to determine explicit expressions for instability of levee body and seepage failure of levee foundation. Finally, Monte Carlo method is introduced to simulate the levee structure stochastically and calculated the comprehensive levee risk. Calculation results of the example show that the risk calculation method proposed in this paper has higher computational efficiency and can provide references for the decision of levee reinforcement.

Accumulating evidence has implicated that constitutive activation of signal transducer and activator of transcription protein 3 (STAT3) may be a major oncogenic factor involved in hepatocellular carcinoma (HCC) development. Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been shown to be a tumor suppressor associated with growth control and suppression of STAT3 activity. The downregulation of GRIM-19 expression has been shown in a number of human tumor types, and it has been correlated with hyperactivation of STAT3. However, the role of GRIM-19 in the pathogenesis of HCC has not been evaluated. The aim of our study was to evaluate GRIM-19 expression levels and investigate their correlation with phosphorylated STAT3 (p-STAT3) levels in HCC. GRIM-19 and p-STAT3 expression levels were analyzed in HCC and adjacent nontumorous liver tissues (ANLT) by immunohistochemistry, western blot analysis, and RT-PCR. GRIM-19 protein expression was predominantly located in the cytoplasm with weak staining in the nucleus in ANLT, but only located in the cytoplasm in HCC tissues. HCC samples exhibited low levels of GRIM-19 and moderate to high levels of p-STAT3 expression. In contrast, ANLT was characterized by high levels of GRIM-19 and low levels of p-STAT3 expression. Downregulation of GRIM-19 was closely correlated with increased histological grade in HCC. GRIM-19 expression is closely correlated with histological grading and p-STAT3 in HCC. Thus, the potential role of GRIM-19 in HCC development may be through these correlations.

Respiratory viruses, including the influenza virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose significant health threats. As tissue-resident macrophages, alveolar macrophages (AM) are crucial for defending against respiratory viral infection by producing cytokines, engulfing virus-infected cells, and promoting wound healing. However, excessive inflammatory responses can lead to tissue injury. Growing evidence indicates that astragaloside IV (AST IV) regulates innate immune responses. Specifically, AST IV balances the inflammatory response to mitigate tissue damage and promote tissue repair. However, whether AST IV directly targets AM to alleviate lung damage induced by respiratory viral infection remains unclear. Our results demonstrate that AST IV treatment significantly reduces morbidity and mortality in mice during IAV infection. AST IV markedly decreases proinflammatory cytokine levels, mitigates lung injury and promotes lung recovery through enhancing the repair capacity mediated by alveolar type II cells. Mechanistically, AST IV suppresses the Wnt/β-catenin signalling pathway, which is critical for driving inflammatory responses in AM while maintaining mitochondrial fitness. Thus, our findings suggest that AST IV effectively targets AM to alleviate inflammation and lung damage caused by respiratory viral infections, highlighting its potential as a therapeutic agent for managing viral pneumonia.

Background Rifampicin-resistant tuberculosis (RR-TB) remains a major public health threat. Nine-month, all-oral regimens containing bedaquiline (Bdq) and linezolid (Lzd) have shown high cure rates, but evidence on the durability of results beyond 24 months and long-term linezolid-induced neurotoxicity is limited. Methods We conducted a multicentre, prospective cohort study (MDR-Chin) involving 124 adults with culture-confirmed MDR/RR-TB or pre-extensively drug-resistant tuberculosis (pre-XDR-TB) enrolled between May 2020 and July 2022. Patients received one of four nine-month, all-oral regimens containing Lzd (600 mg/day). We assessed outcomes 36 months after treatment completion. The primary efficacy outcome was a favourable outcome (absence of failure, relapse, or death). The safety outcome was persistent, clinician-confirmed Lzd-related neuropathic/visual symptoms present for at least 24 months. Results At 36 months after treatment completion, 111 of 124 participants (89.5%, 95% CI 82.9–93.8) achieved a favourable outcome. No significant differences in favourable outcomes were observed between the four regimens (log-rank p  > 0.05). Overall, 28 out of 124 patients (22.6%) reported at least one persistent linezolid-related neuropathic or visual symptom. The most frequent symptom was foot numbness (22/124; 17.7%). Conclusion In this non-randomised multicentre cohort, nine-month all-oral therapy for RR-TB demonstrated durable three-year outcomes. However, linezolid-related persistent neuropathy remained common and warrants proactive mitigation, including optimisation to reduce cumulative linezolid exposure or adoption of linezolid-sparing alternatives when feasible.

BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance. METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence. RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1 high YWHAZ high gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy. CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.