The aim of this paper is to investigate the brittle failure mechanism of rock slopes with non-persistent en-echelon joints using the extended finite element method (XFEM). In the research, a novel ...geometrical method distinguished from the conventional level set method is proposed to describe the cracks in the XFEM. The numerical form of the J-integral considering the effect of the bode force and the frictional contact force is provided. Moreover, a refined coalescence method is proposed. Then, the state function employed to define the state of the crack and the method used to define the crack growth increment are introduced. Next, some numerical tests are carried out to validate the feasibility of the XFEM. Finally, two typical rock slope modes are provided to illustrate the mechanism of the step-path brittle failure of rock slopes.
•A novel geometric method is proposed to describe the cracks in the framework of XFEM.•The numerical form of the J-integral considering the effect of bode force and the frictional contact is derived.•A refined coalescence method is proposed and an empirical method to define the crack growth increment is introduced.•Two typical rock slope modes are provided to illustrate the mechanism of the step-path brittle failure of rock slopes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Developing novel approaches to reverse the drug resistance of tumor-repopulating cells （TRCs） or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we ...show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparficles （T-MPs） containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tu- mor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Increasing evidence shows that mechanical stresses are critical in regulating cell functions, fate, and diseases. However, no methods exist that can quantify isotropic compressive stresses. Here we ...describe fluorescent nanoparticle-labeled, monodisperse elastic microspheres made of Arg-Gly-Asp-conjugated alginate hydrogels (elastic round microgels, ERMGs). We generate 3D displacements and calculate strains and tractions exerted on an ERMG. Average compressive tractions on an ERMG are 570 Pa within cell layers and 360 Pa in tumor-repopulating cell (TRC) colonies grown in 400-Pa matrices. 3D compressive tractions on a 1.4-kPa ERMG are applied by surrounding cells via endogenous actomyosin forces but not via mature focal adhesions. Compressive stresses are substantially heterogeneous on ERMGs within a uniform cell colony and do not increase with TRC colony sizes. Early-stage zebrafish embryos generate spatial and temporal differences in local normal and shear stresses. This ERMG method could be useful for quantifying stresses in vitro and in vivo.
Multimodality optical imaging probes have emerged as powerful tools that improve detection sensitivity and accuracy, important in disease diagnosis and treatment. In this review, we focus on recent ...developments of optical fluorescence imaging (OFI) probe integration with other imaging modalities such as X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and photoacoustic imaging (PAI). The imaging technologies are briefly described in order to introduce the strengths and limitations of each techniques and the need for further multimodality optical imaging probe development. The emphasis of this account is placed on how design strategies are currently implemented to afford physicochemically and biologically compatible multimodality optical fluorescence imaging probes. We also present studies that overcame intrinsic disadvantages of each imaging technique by multimodality approach with improved detection sensitivity and accuracy.
This review is focused on the recent development of optical fluorescence imaging (OFI) probe integrating with imaging contrast agents. The multimodality fluorescence imaging probes are aimed to overcome intrinsic drawbacks of each imaging modality with complementary information from different modalities for improved sensitivity and accuracy, which are important in disease diagnosis and treatment. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autoimmune diseases are a series of diseases involving multiple tissues and organs, characterized by the over production of abnormal multiple antibodies. Although most studies support that the ...impaired immune balance participates in the development of autoimmune diseases, the specific pathogenesis of it is not fully understood. Intestinal immunity, especially the intestinal mucosal barrier has become a research hotspot, which is considered to be an upstream mechanism leading to the impaired immune balance. As an important defense barrier, the intestinal mucosal barrier regulates and maintains the homeostasis of internal environment. Once the intestinal barrier function is impaired under the effect of multiple factors, it will destroy the immune homeostasis, trigger inflammatory response, and participate in the development of autoimmune diseases in the final. However, the mechanism of the intestinal mucosal barrier how to regulate the homeostasis and inflammation is not clear. Some studies suggest that it maintains the balance of immune homeostasis through the zonulin pathway, intestinal microbiome, and Toll-like receptor signaling pathway. Our review focused on the composition and the function of the intestinal mucosal barrier to describe the research progress of it in regulating the immune homeostasis and inflammation, and also pointed that the intestinal mucosal barrier was the potential targets in the treatment of autoimmune diseases.
Lignification of fruit flesh is a common physiological disorder that occurs during post-harvest storage, resulting in the deterioration of fruit quality. Lignin deposition in loquat fruit flesh ...occurs due to chilling injury or senescence, at temperatures around 0°C or 20°C, respectively. Despite extensive research on the molecular mechanisms underlying chilling-induced lignification, the key genes responsible for the lignification process during senescence in loquat fruit remain unknown. MADS-box genes, an evolutionarily conserved transcription factor family, have been suggested to play a role in regulating senescence. However, it is still unclear whether MADS-box genes can regulate the lignin deposition that arises from fruit senescence.
Both senescence- and chilling-induced flesh lignification were simulated by applying temperature treatments on loquat fruits. The flesh lignin content during the storage was measured. Transcriptomic, quantitative reverse transcription PCR and correlation analysis were employed to identify key MADS-box genes that may be involved in flesh lignification. The Dual-luciferase assay was utilized to identify the potential interactions between MADS-box members and genes in phenylpropanoid pathway.
The lignin content of the flesh samples treated at 20°C or 0°C increased during storage, but at different rates. Results from transcriptome analysis, quantitative reverse transcription PCR, and correlation analysis led us to identify a senescence-specific MADS-box gene, EjAGL15, which correlated positively with the variation in lignin content of loquat fruit. Luciferase assay results confirmed that EjAGL15 activated multiple lignin biosynthesis-related genes. Our findings suggest that EjAGL15 functions as a positive regulator of senescence-induced flesh lignification in loquat fruit.
Evolution of eukaryotes from simple cells to complex multicellular organisms remains a mystery. Our postulate is that cytoskeletal stiffening is a necessary condition for evolution of complex ...multicellular organisms from early simple eukaryotes. Recent findings show that embryonic stem (ES) cells are as soft as primitive eukaryotes/amoebae and that differentiated tissue cells can be two orders of magnitude stiffer than ES cells. Soft ES cells become stiff as they differentiate into tissue cells of the complex multicellular organisms to match their microenvironment stiffness. We perhaps see in differentiation of ES cells (derived from inner cell mass cells) the echo of those early evolutionary events. Early soft unicellular organisms might have evolved to stiffen their cytoskeleton to protect their structural integrity from external mechanical stresses while being able to maintain form, to change shape, and to move.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The rational design of electrode structure with catalysts adequately utilized is of vital importance for future fuel cells. Herein, a novel 3D oriented wholly integrated electrode comprising ...core–shell Fe3O4@N‐doped‐C (Fe3O4@NC) nanoparticles embedded into N‐doped ordered interconnected hierarchical porous carbon (denoted as Fe3O4@NC/NHPC) is developed for the oxygen reduction reaction (ORR). The as‐prepared catalyst possesses novel structure and efficient active sites. In rotating disk electrode measurements, the Fe3O4@NC/NHPC exhibits almost identical ORR electrocatalytic activity, superior durability, and much better methanol tolerance compared with the commercial Pt/C in acidic media. To the authors’ knowledge, this is among the best non‐precious‐metal ORR catalysts reported so far. Importantly, the Fe3O4@NC/NHPC is successfully in situ assembled onto carbon paper by the electrophoresis method to obtain a well‐designed 3D‐ordered electrode. With improved mass transfer and maximized active sites for ORR, the 3D‐oriented wholly integrated electrode shows superior performance to the one fabricated by the traditional method.
A 3D oriented wholly integrated electrode is fabricated by the electrophoresis method based on a highly promising Fe‐NX‐C catalyst. Thanks to the rapid mass‐transfer pathway and adequate exposure of catalytic sites, the oxygen reduction reaction performance of the as‐obtained electrode outperforms the electrode fabricated by the traditional electrode preparation method.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting ...microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect.
To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS.
The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6-17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups.
Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection.
Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT.
Retrospectively registered.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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