Under traffic loading, the soil elements in subgrade are subjected to a cyclic cardioid-shaped stress path in the 2τvh~(σv−σh) stress plane. This significantly differs from the conventional stress ...paths that have been simulated using the cyclic triaxial and simple shear apparatuses, as widely reported in the literature. To date, the influence of shear stress level on cyclic deformation behaviour of intact soft clay subjected to cyclic traffic loading were rarely considered in the existing experimental investigation. For this reason, a series of cyclic hollow cylinder experiments that mimic cardioid-shaped stress paths are carried out on intact samples of Wenzhou soft clay. A wide range of vertical stress levels combined with different shear stress levels (i.e., different cardioid-shaped stress paths) are simulated in the experiments. The results show that the shear stress level significantly influences the cyclic straining and exacerbates the potential of cyclic shear failure. The difference of cyclic tests with variable shear stress level increases as the vertical cyclic stress ratio value increases. Based on the test results, an allowable cyclic stress ratio is determined to be about 0.22, which may serve as the upper bound limit of cyclic traffic loadings on soft clayey deposit. For the hollow cylinder specimens used in this study, a resilient axial strain of 3% could be a proper failure criteria value. A simplified permanent strain model that considers shear stress is proposed for the deformation behaviour of soft clay under cyclic traffic loading.
•Static and cyclic tests are conducted on natural clay by hollow cylinder apparatus.•The shear stress level has significant effect on the development of strain.•An allowable cyclic stress ratio is determined for design criterion of pavement.•Experimental model considering principal stress rotation for permanent strain.
Bone regeneration therapy is clinically important, and targeted regulation of endoplasmic reticulum (ER) stress is important in regenerative medicine. The processing of proteins in the ER controls ...cell fate. The accumulation of misfolded and unfolded proteins occurs in pathological states, triggering ER stress. ER stress restores homeostasis through three main mechanisms, including protein kinase-R-like ER kinase (PERK), inositol-requiring enzyme 1ɑ (IRE1ɑ) and activating transcription factor 6 (ATF6), collectively known as the unfolded protein response (UPR). However, the UPR has both adaptive and apoptotic effects. Modulation of ER stress has therapeutic potential for numerous diseases. Repair of bone defects involves both angiogenesis and bone regeneration. Here, we review the effects of ER stress on osteogenesis and angiogenesis, with emphasis on ER stress under high glucose (HG) and inflammatory conditions, and the use of ER stress inducers or inhibitors to regulate osteogenesis and angiogenesis. In addition, we highlight the ability for exosomes to regulate ER stress. Recent advances in the regulation of ER stress mediated osteogenesis and angiogenesis suggest novel therapeutic options for bone defects.
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•The electrostatic force effect mechanism of nanobubbles on the adsorption of collector on graphite surface was revealed.•The mechanism of hydrophobic force effect of nanobubbles on ...the adsorption of collector on graphite surface was revealed.•The flotation mechanism of fine graphite enhanced by nanobubbles was revealed based on the change of graphitesurface properties.
It has been concluded in a recently published investigation that the nanobubble flotation process significantly reduces the number of fine flake graphite flotation stages and improves the flotation performance. The present study was conducted to explore the mechanisms of surface nanobubbles enhancing flake graphite flotation by investigating effects of nanobubbles on surface properties of graphite and interactions between particles and bubbles by use of contact angle analyzer, zeta potential analyzer, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS). The study results show that nanobubbles can improve the surface properties of graphite and enhance the adsorption effect of collector, which increased the contact angle of the graphite surface by 11.93° compared with conventional flotation. Infrared spectroscopy and potential analysis showed that the nanobubbles could enhance the hydrophobic attraction and reduce the electrostatic repulsion between the collector and the graphite surface, which was beneficial to enhance the hydrophobic surface of the graphite and enhance the agglomeration of fine graphite particles. XPS analysis showed that the nanobubbles covered polar hydrophilic groups (such as CO, CO, COOH) on the graphite surface, which enhanced the adsorption of collector to improve the hydrophobicity of graphite surface.
Since the alarming settlement of transport infrastructures on soft subgrade caused by long-term traffic loading, a method for predicting settlement is of considerable significance in the engineering ...design. In this study, we proposed a practical and simple predicting method on the settlement of soft subgrade considering traffic loading effects. The model used in this method involves the principal stress rotation and loading frequency, which needs only four parameters with clear meaning obtained by several cyclic triaxial tests. The applicability of the model has been verified by previous results from other researchers. Moreover, the engineering practicality of this method was validated by the field data of a highway. The settlements under low-frequency and high-frequency are the upper limit and lower limit of the traffic load-induced settlements, respectively. With the increasing embankment thickness, the settlements decrease because the cyclic stress ratio decreases and the detrimental effect of the principal stress rotation on the settlement reduces. The vehicle load is a more influential factor in the settlement than the traffic volume.
•Develop a new empirical model on permanent strain considering PSR and f.•The model parameters with clear meaning can be determined by only 4 CT tests.•The calculation with this model agrees well with the field settlement.•The embankment thickness, vehicle speed, and load affect the settlement most.
Objective To explore the relationship between pyroptosis and treatment in non-small cell lung cancer patients treated with tyrosine kinase inhibitors targeted therapy. Methods Stable transfection ...strains with common EGFR mutations found in clinical practice were constructed through lentiviral transfection. LDH and Western blot experiments were conducted to determine the degree and mechanism of pyroptosis after osimertinib treatment. Animal experiments verified the effect of pyroptosis on treatment efficacy. ELISA was used to explore the potential connection between pyroptosis and tumor immunotherapy. Results After osimertinib treatment on stable lines, the EGFR-L858R mutation had obvious pyroptosis at the morphology and protein levels. Western blot experiment confirmed that pyroptosis was mediated by GSDME (P<0.0001). Experiments through the overexpression of GSDME and corresponding animal studies discovered that the degree of pyroptosis affected the treatment outcome. Blood analysis revealed that the level o
Cables are indispensable in nuclear power plants for transmitting data measured by various types of detectors, such as self-powered neutron detectors (SPNDs). These cables will generate disturbing ...signals that must be accurately distinguished and eliminated. Given that the cable current is not very significant, previous research has focused on SPND, with little attention paid to cable evaluation and validation. This paper specifically focuses on the quantitative analysis of cables and proposes a theoretical model to predict cable noise. In this model, the reaction characteristics between irradiated neutrons and cables were discussed thoroughly. Based on the Monte Carlo method, a comprehensive simulation approach of neutron sensitivity was introduced and long-term irradiation experiments in a heavy water reactor (HWR) were designed to verify this model. The theoretical results of this method agree quite well with the experimental measurements, proving that the model is reliable and exhibits excellent accuracy. The experimental data also show that the cable current accounts for approximately 0.2% of the total current at the initial moment, but as the detector gradually depletes, it will contribute more than 2%, making it a non-negligible proportion of the total signal current.
The treatment for metastatic castration-resistant prostate cancer patients remains a great challenge in the clinic and continuously demands discoveries of new targets and therapies. Here, we assess ...the function and therapeutic value of SIRT6 in metastatic castration-resistant prostate cancer.
The expression of SIRT6 was examined in prostate cancer tissue microarray by immunohistochemistry staining. The functions of SIRT6 and underlying mechanisms were elucidated by
and
experiments. We also developed an efficient method to silence SIRT6 by aptamer-modified exosomes carrying small interfering RNA and tested the therapeutic effect in the xenograft mice models.
SIRT6 expression is positively correlated with prostate cancer progression. Loss of SIRT6 significantly suppressed proliferation and metastasis of prostate cancer cell lines both
and
. SIRT6-driven prostate cancer displays activation of multiple cancer-related signaling pathways, especially the Notch pathway. Silencing SIRT6 by siRNA delivered through engineered exosomes inhibited tumor growth and metastasis.
SIRT6 is identified as a driver and therapeutic target for metastatic prostate cancer in our findings, and inhibition of SIRT6 by engineered exosomes can serve as a promising therapeutic tool for clinical application.
Vanadium self-powered neutron detectors (SPNDs) are widely used as in-core unmovable detectors in nuclear power plants to continuously carry out data monitoring of neutron flux and nuclear power. In ...this study, a theoretical calculation model is presented for determining the signal current and thermal neutron sensitivity of vanadium SPNDs. First, the physical characteristics and reaction mechanisms in vanadium SPNDs irradiated with neutrons were discussed thoroughly. Then, a computational approach to determine the neutron sensitivity of the vanadium SPND based on a Monte Carlo method without assumptions and approximations was introduced. Finally, in order to verify the performance of the vanadium SPND and our methodology, the calculated values were compared with experimental measurements and the previous literature. It can be found that all the results agree well with the experimental measurements and that the maximum differences do not exceed 3%, which demonstrates the reliability and effectiveness of the method and further improves the calculation accuracy.
Background Macrophages play a pivotal role in the research landscape of non-small cell lung cancer (NSCLC), contributing significantly to understanding tumor progression, treatment resistance, and ...immunotherapy efficacy. In this study, we utilized bibliometric techniques to analyze shifts in research hotspots and trends within the field, while also forecasting future research directions. These insights aim to offer guidance for both clinical therapeutic interventions and foundational scientific inquiries. Methods All publications were released between 1993 and 2023 and focus on research pertaining to macrophages in the field of NSCLC. The articles were identified from the Web of Science Core Collection and analyzed using VOSviewer 1.6.19, CiteSpace 6.2.R2, and Scimago Graphica 1.0.35. Result A total of 361 articles authored by 3,072 researchers from 48 countries were included in the analysis. TAMs have gained increasing attention for their role in NSCLC development and as potential therapeutic targets. Modulating TAM behavior may offer avenues to suppress tumor growth and drug resistance, improving patient outcomes. International collaboration, particularly between China and the United States, accelerates progress in NSCLC research, benefiting patients worldwide. The research hotspot revolves around understanding the role of macrophages in immunotherapy, focusing on their contribution to tumor progression, therapeutic resistance, and potential as therapeutic targets in NSCLC. Conclusions The therapeutic significance of macrophages in the field of NSCLC is gaining increasing attention and recognition, highlighting their potential as key players in the development of novel treatment strategies. Future research will focus on understanding TAM molecular mechanisms, interactions with immune cells, and exploring novel therapies, with the aim of improving NSCLC treatment outcomes.
Osteosarcoma (OS), the primary malignant bone tumor, has a low survival rate for recurrent patients. Latest reports indicated that cancer-associated fibroblasts (CAFs) were the main component of ...tumor microenvironment, and would generate a variable role in the progression of tumors. However, the role of CAFs is still few known in osteosarcoma.
The processed RNA-seq data and the corresponding clinical and molecular information were retrieved from the Cancer Genome Atlas Program (TCGA) database and processed data of tumor tissue was obtained from Gene Expression Omnibus (GEO) database. Xcell method was used in data processing, and Gene set variation analysis (GSVA) was used to calculates enrichment scores. Nomogram was constructed to evaluate prognostic power of the predictive model. And the construction of risk scores and assessment of prognostic predictive were based on the LASSO model.
This study classified Cancer Genome Atlas (TCGA) cohort into high and low CAFs infiltrate phenotype with different CAFs infiltration enrichment scores. Then TOP 9 genes were screened as prognostic signatures among 2,488 differentially expressed genes between the two groups. Key prognostic molecules were CGREF1, CORT and RHBDL2 and the risk score formula is: Risk-score = CGREF1*0.004 + CORT*0.004 + RHBDL2*0.002. The signatures were validated to be independent prognostic factors to predict tumor prognosis with single-factor COX and multi-factor COX regression analyses and Norton chart. The risk score expression of risk score model genes could predict the drug resistance, and significant differences could be found between the high and low scoring groups for 17-AAG, AZD6244, PD-0325901 and Sorafenib.
To sum up, this article validated the prediction role of CAF infiltration in the prognosis of OS, which might shed light on the treatment of OS.
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