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Background: The primary objective of this study was to evaluate the predictive and prognostic value of serum lipids in recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients received anti‐PD‐1 therapy. Materials and Methods: Patients treated with anti‐PD‐1 therapy (monotherapy or combined with chemotherapy) from two clinical trials (CAPTAIN and CAPTAIN‐1st study) were included. Serum lipids were measured at baseline and after two cycles of treatment. We examined the impact of both baseline and post‐treatment lipid levels on objective response rate (ORR), progression‐free survival (PFS), and duration of response (DOR). Results: Of 106 patients, 89 patients (84%) were male. The patients' median age was 49 years. An early elevated (after two cycles of treatment) cholesterol (CHO), low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein A‐I (ApoA‐I), and apolipoprotein B (ApoB) were significantly associated with better ORR. Moreover, early elevated CHO, LDL‐C, and ApoA‐I were also positively correlated with DOR and PFS. Further multivariate analysis showed that only early change in ApoA‐I could independently predict PFS (HR, 2.27; 95% CI, 1.11–4.61; p = 0.034). The median PFS for patients with early elevated and reduced ApoA‐I was 11.43 and 1.89 months, respectively. However, baseline lipids levels do not play a significant role in the prognosis and prediction of patients with anti‐PD‐1 treatment. Conclusion: Collectively, an early elevation in ApoA‐I was correlated with better outcomes for anti‐PD‐1 therapy in patients with R/M NPC, suggesting that clinicians should consider the early alteration of ApoA‐I as a useful marker in treating R/M NPC patients with anti‐PD‐1. [ABSTRACT FROM AUTHOR]

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release. [ABSTRACT FROM AUTHOR]

A novel nonlocal thermo‐hydro‐mechanical coupling model is proposed to investigate cracking behaviors of quasi‐brittle materials in the framework of advanced general particle dynamics (GPD). The nonlocal thermal conduction equation and the nonlocal flow diffusion equation are derived based on nonlocal vector calculus and the microscopic constitutive equation. Moreover, the coupling influences are considered based on the nonlocal equation and the coupling principle. The governing equation of the coupling system is established in the framework of GPD. The correctness of the proposed model is verified through comparing with the corresponding experimental data, and the numerical results are in good agreement with experimental results. Finally, the proposed model is applied to analyze the deformation and cracking behaviors of rock mass around tunnels, and the stress redistribution is revealed under thermo‐hydro‐mechanical coupling condition. Highlights: A novel nonlocal thermo‐hydro‐mechanical coupling model is proposed to investigate the cracking behaviors of rocks.The nonlocal thermal conduction equation and the nonlocal flow diffusion equation are derived.The governing equation of the coupling system is established in the framework of advanced general particle dynamics. [ABSTRACT FROM AUTHOR]

Under the influence of rainfall, the failure mechanism and stability of layered slopes is one of the current hot topics. This paper aims to examine the influence of rainstorm conditions on the stability of layered soil slopes and analyze the inter infiltration rule and water-holding response characteristics through physical model tests and numerical simulation. The results demonstrate that the layered structure and inclination can affect the rainwater infiltration and stability of layered soil slopes under rainstorm conditions. Different inclinations greatly influence the safety factors of the layered soil slopes and the downdip slopes are more susceptible to landslides due to heavy rainfall. Meanwhile, the pore water pressure of the sand layer dissipates 90.95% and 70.45% under the horizontal layer and downdip layer, respectively. In addition, settlement occurs on the surface of the slope at the initial stage of rainfall. As rainwater continuously infiltrates, the slope’s surface expands unevenly. The expansion amplitudes of the shoulder and toe of the slope have a more extensive expansion range, which is crucial in landslide prevention and control. The results of the model test are consistent with the numerical simulation analysis. The results provide a theoretical basis for designing a stratified soil slope management plan. [ABSTRACT FROM AUTHOR]

Background: The Parkland Grading Scale (PGS) is an intraoperative grading scale to stratify gallbladder disease severity during laparoscopic cholecystectomy (LC). We evaluated the usefulness of the PGS in predicting the difficulty levels of LC procedures using a novel approach. Methods: A total of 261 patients diagnosed with cholelithiasis and cholecystitis who underwent LC were assessed. The PGS and the surgical difficulty grading system were used to evaluate surgical procedures by reviewing the operation videos. Clinical baseline characteristics and post-treatment outcomes were also recorded. Differences between the five PGS grades in terms of surgical difficulty scores were analyzed using the Jonckheere-Terpstra test. The relationship between PGS grades and surgical difficulty scores was assessed using Spearman's Rank correlation. Finally, the linear trends between morbidity scores and PGS grades were evaluated using the Mantel-Haenszel test. Results: There was a significant difference in the surgical difficulty scores for the five PGS grades (p < 0.001). In pairwise comparison, each grade (1–5) was significantly different from the others (p < 0.05) in terms of surgical difficulty, except Grade 2 vs. 3 (p = 0.07) and Grade 3 vs. 4 (p = 0.08). There was a significant correlation between PGS grades and surgical difficulty scores (rs = 0.681, p < 0.001). There was also a significant linear association between morbidity and PGS grades (p < 0.001). Spearman's R value was 0.176 (p = 0.004). Conclusion: The PGS can accurately assess the surgical difficulty level of LC. The precision and conciseness of the PGS make it suitable for use in future research. [ABSTRACT FROM AUTHOR]

Under the action of a load, internal pores and cracks expand, and irreversible plastic deformations occur. Compared with conventional rock mechanics tests, nuclear magnetic resonance (NMR) can characterize the size and distribution of pores at the microscopic scale. In this study, a series of low-confining-stress triaxial compression tests were performed on different types of sandstone samples using real-time T2-weighted NMR spectra and imaging. It was found that the area of macropores in sandstone significantly increased only during the initial loading stage, but played an opposite role in the damage evolution process. This phenomenon is contrary to our expectations and provides a new basis for understanding the evolution of damage in rocks. Furthermore, during the linear deformation stage, the number of pores and mesopores increased, whereas the number of macropores decreased. A damage model based on the NMR results is proposed. The value of Dn sharply increases during the initial stage due to the expansion of pores, then decreases, and finally begins to increase again before the failure stage and until the sample fractures owing to the development of macroscopic cracks. In conclusion, the structure of micropores has a significant influence on the failure mode of sandstone rocks in low-confining-pressure triaxial compression tests. Highlights: The area of macropores in sandstone significantly increased only during the initial loading stage and played an opposite role in the damage evolution process. During the linear deformation stage, the number of pores and mesopores increased, whereas the number of macropores decreased. The structure of micropores has a significant influence on the failure mode exhibited by sandstone during low-confining-pressure triaxial compression tests. [ABSTRACT FROM AUTHOR]

Multiple recursive generators are an important class of pseudorandom number generators which are widely used in cryptography. Methods to predict the whole sequences by the truncated high-order bits of the sequences are not only a crucial aspect of evaluating the security of pseudorandom number generators but also important concerns in the design of pseudorandom number generators. This paper improves the work of Sun et al. (Des Codes Cryptogr 88:1083–1102, 2020) on the predictability of truncated multiple recursive generators with unknown parameters. Given a few truncated digits of high-order bits output by a multiple recursive generator, we first apply the resultant to recover the modulus, then use the Chinese Remainder Theorem and the idea of recovering p-adic coordinates of the coefficients layer by layer to recover the coefficients, and finally employ Kannan's embedding technique to recover the initial state. Experimental results show that our new method is superior to that of Sun et al. (2020), no matter in terms of the running time or the number of truncated digits required. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC. Aberrant EGFR expression is associated with triple-negative breast cancer (TNBC). Here the authors identify that TMEM25 interacts with EGFR and the loss of TMEM25 allows monomeric EGFR-mediated hyperactivation of STAT3 to promote TNBC progression. [ABSTRACT FROM AUTHOR]

The microwave-assisted rock breaking technology has been proven to be feasible, and has received considerable attention in the field of civil and mining engineering. A copper foil was used to wrap basalt to simulate rock excavation of practical application scenario in this paper. To this end, a multi-mode cavity with an operating frequency of 2.45 GHz was used to conduct microwave irradiation experiments on basalts with different irradiation times and different power. The thermal properties, AE characteristics, and damage evolution process of basalt were studied. The results show that the high heat generated by microwave leads to the development of cracks in the upper part of basalt. The higher the power level, the higher the degree of crack propagation in the sample, the lower the basalt strength, and the more active the AE activity. The fluctuation rule of the b value indicates that the basalt is dominated by small-scale microfractures before failure. High power levels or long irradiation time lead to more microwave-induced cracks participating in the failure process during loading. Compared with unheated basalt, microwave-heating basalt detects the characteristics of the precursor of failure in advance. The AE source location and the nephogram of the maximum principal stress of microwave-treated basalt reflected that the fracture path begins in the upper part of the rock. In addition, the combination of high power level and short irradiation time can achieve the purpose of energy saving. [ABSTRACT FROM AUTHOR]

Periodical cyclic loads are often encountered in the construction and operation stages of geotechnical engineering. In the paper, multi-level triaxial cyclic loading and unloading (TCLU) compression tests are conducted on sandstone samples under varying upper limits of axial stress. Firstly, the crack volumetric (deviatoric) strain curves and the characteristic stresses are obtained, and the evolution curves of the hysteresis loop, the characteristic of crack strain, and axial (radial) strain are analyzed. Secondly, the strain evolution equation has been applied to the fitting analysis of 125 groups of axial and radial strain data, and good results were obtained. The equation has better applicability to TCLU tests. Finally, the damage evolution law, life prediction of the sandstone, and failure mechanism are revealed. Studies show that: after the crack initiation stress is exceeded, the crack radial strain and the crack axial strain curves gradually show an obvious nonlinear phenomenon with the increase of axial stress. By fitting the evolution process of the axial (radial) strain, it clarified the coupling action of axial stress and confining pressure on the fatigue failure of sandstone. The damage factor of each sample shows a step growth, and the development of the radial damage factor lags behind the axial damage factor. Upper limits of axial stress value are key factors in determining the fatigue life of rocks. The rock failure mode under the TCLU path is mainly manifested as splitting tension failure and shear failure. The fatigue life is predicted by fitting and analyzing the rock strain evolution equation under the action of TCLU using damage mechanics theory combined with experimental data, which will help to understand the failure mechanism of rock mass, and then scientifically evaluate the long-term stability of engineering rock mass. Highlights: The evolution law of mechanical parameters, hysteresis loop, crack evolution characteristics, damage evolution law, and failure mode analysis of the sandstone are researched during multi-level triaxial cyclic loading and unloading under varying stress limits. This paper regards strain as the controlling factor of triaxial fatigue damage of sandstone, focuses on the entire fatigue damage process, and analyzes the dynamic development law of fatigue strain and damage subjected to multi-level triaxial cyclic loading and unloading conditions. The fatigue life is predicted by fitting and analyzing the rock strain development evolution model under multi-level triaxial cyclic loading and unloading with experimental data using damage mechanics theory, it contributes to understanding the failure mechanism of rock mass, and then scientifically evaluating the long-term stability of engineering rock mass. [ABSTRACT FROM AUTHOR]