The vibrational characteristics of multilayer magnetic nanocomposite beams reinforced by graphene nanoplatelets (GPLs) are analytically investigated in this paper. The effects of an elastic ...foundation are also studied. The material properties of piece-wise GPL-reinforced nanocomposites (GPLRCs) are assumed to be graded in the thickness direction of the beams and can be estimated by using the modified Halpin–Tsai model and rules of mixtures. The two-dimensional elasticity theory is adopted to derive the governing equation combined with the state space method, and the analytical frequency equations for simply supported beams are obtained. In addition, the effects of a magnetic field are involved via Maxwell’s equation, and the corresponding Lorentz forces are considered in this work. Numerical examples are carried out to examine the effects of magnetic fields in various directions, the GPL distribution pattern, the scale parameter and weight function of GPLs, as well as an elastic foundation, on the vibration behaviors of functionally graded (FG)-GPLRC beams.
Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor ...progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic.
Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential.
Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity.
The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC.
This paper focuses on the size-dependent free vibration and buckling behaviors of the axially functionally graded (AFG) graphene platelets (GPLs) reinforced nanocomposite microbeams subjected to ...axially varying loads (AVLs). With various axial grading patterns, the GPL nano-reinforcements are distributed throughout the polymer matrix against microbeam length, and the improved Halpin-Tsai micromechanics model and the rule of mixture are adopted to evaluate the effective material properties. Eigenvalue equations of the microbeams governing the static stability and vibration are derived based on the modified couple stress Euler-Bernoulli beam theory via the state-space method, and are analytically solved with the discrete equilong segment model. The effects of axial distribution patterns, weight fraction, and geometric parameters of GPLs, as well as different types of AVLs, on the size-dependent buckling load and natural frequency are scrutinized in detail. The results show that the synchronized axial distributions of GPLs and AVLs could improve the buckling resistance and natural frequency more powerfully.
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. Hepatitis B virus (HBV) infection accounts for nearly 50% of HCC cases. Recent studies indicate that HBV infection induces ...resistance to sorafenib, the first-line systemic treatment for advanced HCC for more than a decade, from 2007 to 2020. Our previous research shows that variant 1 (tv1) of proliferating cell nuclear antigen clamp-associated factor (PCLAF), overexpressed in HCC, protects against doxorubicin-induced apoptosis. However, there are no reports on the relevance of PCLAF in sorafenib resistance in HBV-related HCC. In this article, we found that PCLAF levels were higher in HBV-related HCC than in non-virus-related HCC using bioinformatics analysis. Immunohistochemistry (IHC) staining of clinical samples and the splicing reporter minigene assay using HCC cells revealed that PCLAF tv1 was elevated by HBV. Furthermore, HBV promoted the splicing of PCLAF tv1 by downregulating serine/arginine-rich splicing factor 2 (SRSF2), which hindered the inclusion of PCLAF exon 3 through a putative
-element (116-123), "
". The CCK-8 assay showed that HBV decreased cell susceptibility to sorafenib through SRSF2/PCLAF tv1. HBV reduced ferroptosis by decreasing intracellular Fe
levels and activating GPX4 expression via the SRSF2/PCLAF tv1 axis, according to a mechanism study. Suppressed ferroptosis, on the other hand, contributed to HBV-mediated sorafenib resistance through SRSF2/PCLAF tv1. These data suggested that HBV regulated PCLAF abnormal alternative splicing by suppressing SRSF2. HBV caused sorafenib resistance by reducing ferroptosis via the SRSF2/PCLAF tv1 axis. As a result, the SRSF2/PCLAF tv1 axis may be a prospective molecular therapeutic target in HBV-related HCC, as well as a predictor of sorafenib resistance. The inhibition of the SRSF2/PCLAF tv1 axis may be crucial in the emergence of systemic chemotherapy resistance in HBV-associated HCC.
Two targets of NopT from Mesorhizobium amphore CCNWGS0123 were identified in Robinia pseudoacacia. Hypersensitive-induced response protein potentially participated in the alteration of the plant ...cytoskeleton to facilitate rhizobial infection.
Abstract
Nodulation outer proteins secreted via type 3 secretion systems are involved in the process of symbiosis between legume plants and rhizobia. To study the function of NopT in symbiosis, we mutated nopT in Mesorhizobium amphore CCNWGS0123 (GS0123), which can nodulate black locust (Robinia pseudoacacia). The nopT mutant induced higher levels of jasmonic acid, salicylic acid, and hydrogen peroxide accumulation in the roots of R. pseudoacacia compared with wild-type GS0123. The ΔnopT mutant induced higher disease-resistant gene expression 72 hours post-inoculation (hpi), whereas GS0123 induced higher disease-resistant gene expression earlier, at 36 hpi. Compared with the nopT mutant, GS0123 induced the up-regulation of most genes at 36 hpi and the down-regulation of most genes at 72 hpi. Proteolytically active NopT_GS0123 induced hypersensitive responses when expressed transiently in tobacco leaves (Nicotiana benthamiana). Two NopT_GS0123 targets in R. pseudoacacia were identified, ATP-citrate synthase alpha chain protein 2 and hypersensitive-induced response protein. Their interactions with NopT_GS0123 triggered resistance by the plant immune system. In conclusion, NopT_GS0123 inhibited the host plant immune system and had minimal effect on nodulation in R. pseudoacacia. Our results reveal the underlying molecular mechanism of NopT function in plant–symbiont interactions.
Increasing studies have demonstrated that microRNAs (miRNAs) are associated with the metastasis of gallbladder carcinoma (GBC). Recently, miR-324-5p has been reported to be a tumour-suppressive miRNA ...in many types of malignant cancer. However, the biological function and molecular mechanism of miR-324-5p in GBC still remain largely unknown. Here, we found that miR-324-5p expression was notably down-regulated in both GBC tissues and cells compared with that in normal controls. Downregulated miR-324-5p expression was negatively associated with the status of local invasion and lymph node metastasis and predicted a poor prognosis in GBC patients. Further functional assays revealed that restoration of miR-324-5p significantly suppressed GBC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and impeded the metastasis of GBC cells in vivo. Moreover, RNA immunoprecipitation (RIP) and dual-luciferase reporter assay confirmed that the transforming growth factor beta 2 (TGFB2) was a direct target gene of miR-324-5p in GBC cells. Mechanically, small interfering RNA (siRNA)-mediated knockdown of TGFB2 partially phenocopied the inhibitory effects of miR-324-5p overexpression on GBC cell metastatic phenotypes. In summary, our findings demonstrated that miR-324-5p targets TGFB2 expression to inhibit GBC cell metastatic behaviors, and implying miR-324-5p as a potential biomarker for diagnostic and therapeutic strategies in GBC.
Background
Glioma is the most common intracranial malignancy in adults with a high degree of malignancy and poor prognosis, which is largely attributed to the existence of glioma stem cells (GSCs). ...Previous evidence indicated that the matrix metalloproteinase ADAMTS1 was implicated in the process of tumor invasion, but the involvement of ADAMTS1 in glioma malignant invasion remains poorly understood.
Methods
The expression and prognosis values of ADAMTS1 were investigated in patients with glioma based on ONCOMINE and GEPIA databases. ADAMTS1 expression of different malignancy grade tissues was determined by immunohistochemistry. The effects of ADAMTS1 on cell proliferation and invasion were determined by clone formation assay and Transwell migration assay. The animal experiment was performed in an intracranial orthotopic xenograft model by knockout of ADAMTS1. Stemness properties and Notch1-SOX2 pathway were examined in stable ADAMTS1 knockdown GSCs.
Results
The expression levels of ADAMTS1 were significantly higher in glioma tissues and significantly correlated with the grade of malignancy and prognosis of glioma. Elevated ADAMTS1 expression was associated with SOX2, N-cadherin and the resistance of chemoradiotherapy of glioma patients. ADAMTS1 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Mechanistically, we found a blockade of the migration and invasiveness of GSCs and the expression levels of Notch1 and SOX2 in absence of ADAMTS1.
Conclusion
As a biomarker for prediction of prognosis, ADAMTS1 may affect the invasive phenotype of GSCs by regulating Notch1-SOX2 signaling pathway, thereby promoting the invasive growth of glioma.
Based on the first-order shear deformation theory (FSDT) and Kelvin–Voigt viscoelastic model, one derives a wave equation of longitudinal guide waves in viscoelastic orthotropic cylindrical shells, ...which analytically solves the wave equation and explains the intrinsic meaning of the wave propagation. In the numerical examples, the velocity curves of the first few modes for the elastic cylindrical shell are first calculated, and the results of the available literature are compared to verify the derivation and programming. Furthermore, the phase velocity curves and attenuation coefficient curves of the guide waves for a functionally graded (FG) shell are calculated, and the effects of viscoelastic parameters, material gradient patterns, material volume fractions, and size ratios on the phase velocity curves and attenuation curves are studied. This study can be widely used to analytically model the wave propagating in inhomogeneous viscoelastic composite structures and present a theoretical basis for the excellent service performance of composite structures and ultrasonic devices.
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•Lower crustal flow plays an important role in the crustal deformation of the Sichuan-Yunnan region.•The modeled results comply with the GPS observations when the velocity of the ...lower crustal flow is approximately 10–11mm/a higher than the upper crust.•The best fitting is achieved when the viscosity coefficients of the middle and lower crust in the South China block are 1022Pa.s and 1023Pa.s, respectively.•The results indicate the decoupling between the crust and mantle in western Sichuan region.
The characteristics of crustal deformation and its dynamical mechanisms in the Sichuan-Yunnan region are of interest to many researchers because they can help explain the deformation pattern of the eastern Tibetan Plateau. In this paper, we employ a precise three-dimensional viscoelastic finite element model to simulate the crustal deformation in the Sichuan-Yunnan region, southeastern Tibetan Plateau. We investigate the influence of lower crustal flow and rheological variations by comparing the modeled results with GPS observations. The results demonstrate that lower crustal flow plays an important role in crustal deformation in the Sichuan-Yunnan region. The best fitting is achieved when the flow velocity of the lower crust is approximately 10–11mm/a faster than that of the upper crust. Additionally, crustal rheological properties affect regional crustal deformation. When the viscosity of the middle and lower crust in the South China block reaches 1022 and 1023Pa·s, respectively, the modeled results match observations well, especially for the magnitude of crustal motion within the South China block. Finally, our dynamic model shows that the maximum principal stress field of the Sichuan-Yunnan region exhibits clear zoning, gradually shifting from an approximately east-west orientation in the northern Bayan Har block to southeast in the South China block, southwest in the western Yunnan block, and a radially divergent distribution in the Middle Yunnan and Southern Yunnan blocks.
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