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Pan-vascular diseases, based on systems biology theory, explore the commonalities and individualities of important target organs such as cardiovascular, cerebrovascular and peripheral blood vessels, starting from the systemic and holistic aspects of vascular diseases. The purpose is to understand the interrelationships and results between them, achieve vascular health or sub-health, and comprehensively improve the physical and mental health of the entire population. Post-translational modification (PTM) is an important part of epigenetics, including phosphorylation, acetylation, ubiquitination, methylation, etc., playing a crucial role in the pan-vascular system. Crotonylation is a novel type of PTM that has made significant progress in the research of pan-vascular related diseases in recent years. Based on the review of previous studies, this article summarises the various regulatory factors of crotonylation, physiological functions and the mechanisms of histone and non-histone crotonylation in regulating pan-vascular related diseases to explore the possibility of precise regulation of crotonylation sites as potential targets for disease treatment and the value of clinical translation.
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Waveguide metatronics, known as an advanced platform of metamaterial-inspired circuits, provides a promising paradigm for millimeter-wave and terahertz integrated circuits in future fifth/sixth generation (5/6G) communication systems. By exploiting the structural dispersion properties of waveguides, a lumped type of waveguide integrated elements and circuits could be developed in deep subwavelength scales with intrinsic low loss and low crosstalk. In this study, we focus on constructing negative capacitors and inductors for waveguide metatronics, effectively expanding the operating frequency range of waveguide integrated circuits. The incorporation of negative elements enables wideband impedance matching in waveguide, which have been both theoretically explored and experimentally validated within the waveguide metatronics paradigm. Furthermore, we have demonstrated that the negative elements can also be realized in the optical domain through the utilization of a silicon waveguide with photonic crystal cladding, indicating the feasibility and universality of wideband waveguide metatronics. The negative lumped elements could boost the progress of the waveguide metatronic technique, achieving superior performance on the conventional lumped circuits within waveguides that solely rely on positive elements.
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Supercoupling effect is an exotic and counterintuitive physical phenomenon of epsilon-near-zero (ENZ) media, in which the light can be "squeezed" and tunneled through flexible channels substantially narrower than its wavelength. Theoretically, ENZ channels with infinitely small widths perform ideal supercoupling with full energy transmission and zero-phase advance. As a feasible solution to demonstrate ENZ supercoupling through a finite-width channel, photonic doping can assist the light in squeezing, but the resonant dopant introduces inevitable losses. Here, we propose an approach of transmission-type photonic doping to achieve proximate ideal ENZ supercoupling. In contrast to the conventional resonance-type photonic doping, our proposed transmission-type doping replaces high-quality-factor two-dimensional resonant doping modes with low-quality-factor one-dimensional modes, such that obviously high transmission efficiency and zero-phase advance in ENZ supercoupling is achieved and observed in experiments. Benefiting from the high-efficiency ENZ supercoupling, waveguides with near-total energy transmission can be engineered with arbitrary dimensions and shapes, serving as flexible power conduits in the paradigm of waveguide integrated circuits for future millimeter-wave and terahertz integrated circuit innovations.
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Cholangiocarcinoma (CCA) with a high malignancy is usually diagnosed as advanced and is prone to metastasis and leads to a poor prognosis. It is reported that cordycepin has anti-tumor effect. However, the molecular targets and mechanisms of cordycepin in inhibiting CCA metastasis remains unclear. In order to evaluate the therapeutic effect of cordycepin on CCA metastasis, experiments were conducted in vivo and in vitro. The results showed that cordycepin inhibited the migration and EMT progression of HuCCT1 and QBC939 cells. Cordycepin has a strong hypolipidemic effects, therefore, we examined its effect on lipid metabolism in CCA. Cordycepin inhibits SREBP1 mediated fatty acid synthesis through the AKT/mTOR signaling pathway. Meanwhile, cordycepin can reduce ERO1A expression in HuCCT1 and QBC939 cells. ERO1A plays a role in malignant tumors. ERO1A promotes migration and lipid metabolism of CCA cells through AKT/mTOR signaling pathway. In addition, cordycepin significantly inhibited the tumor metastasis and the serum levels of TG and T-CHO in mice. Taken together, we demonstrate that cordycepin mediated ERO1A/mTOR/SREBP1 axis inhibits lipid metabolism and metastasis in CCA cells in vitro and in vivo. These data suggest that cordycepin can be used as a novel drug for the clinical treatment of CCA and to improve the prognosis.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Animales , Ratones , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Colangiocarcinoma/metabolismo , Metabolismo de los Lípidos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Humanos , Transición Epitelial-MesenquimalRESUMEN
The self-mixing interference (SMI) signal carries the information of the external moving object, which has great physical significance and application prospects for extracting and analyzing the information of the external object. In this paper, we propose a vibration measurement method based on a reverse point recognition algorithm on the SMI laser signal. By extracting and analyzing the hill and valley values of the SMI signal to determine the reverse point, combined with the semifringe counting method, the vibration information of external objects can be accurately extracted. The method we propose simplifies the displacement reconstruction process with high accuracy. The simulation and experimental results show that this method can achieve high-precision measurements of microvibration with an absolute error of less than 19 nm.
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Cholangiocarcinoma (CCA) is a malignant tumor that arises from the epithelial cells of the bile duct and is notorious for its poor prognosis. The clinical outcome remains disappointing, and thus more effective therapeutic options are urgently required. Cordycepin, a traditional Chinese medicine, provides multiple pharmacological strategies in antitumors, but its mechanisms have not been fully elucidated. In this study, we reported that cordycepin inhibited the viability and proliferation capacity of CCA cells in a time- and dose-dependent manner determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assay. Flow cytometry and Hoechst dye showed that cordycepin induced cancer cell apoptosis via extracellular signal-regulated kinase (ERK) 1/2 deactivation. Moreover, cordycepin significantly reduced the angiogenetic capabilities of CCA in vitro as examined by tube formation assay. We also discovered that cordycepin inhibited DEK expression by using Western blot assay. DEK serves as an oncogenic protein that is overexpressed in various gastrointestinal tumors. DEK silencing inhibited CCA cell viability and angiogenesis but not apoptosis induction determined by Western blot and flow cytometry. Furthermore, cordycepin significantly inhibited tumor growth and angiogenic capacities in a xenograft model by downregulating the expression of DEK, phosphorylated ERK1/2 CD31 and von Willebrand factor (vWF). Taken together, we demonstrated that cordycepin inhibited CCA cell proliferation and angiogenesis with a DEK interaction via downregulation in ERK signaling. These data indicate that cordycepin may serve as a novel agent for CCA clinical treatment and prognosis improvement. SIGNIFICANCE STATEMENT: Cordycepin provides multiple strategies in antitumors, but its mechanisms are not fully elucidated, especially on cholangiocarcinoma (CCA). We reported that cordycepin inhibited the viability of CCA cells, induced apoptosis via extracellular signal-regulated kinase 1/2 deactivation and DEK inhibition, and reduced the angiogenetic capabilities of CCA both in vivo and in vitro.
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Neoplasias de los Conductos Biliares/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Proteínas Cromosómicas no Histona/antagonistas & inhibidores , Desoxiadenosinas/farmacología , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neovascularización Patológica/prevención & control , Proteínas Oncogénicas/antagonistas & inhibidores , Proteínas de Unión a Poli-ADP-Ribosa/antagonistas & inhibidores , Animales , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma/patología , Humanos , Masculino , Ratones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
ABSTRACT: Endoplasmic reticulum oxidoreductase 1-α (ERO1A) is a kind of hypoxia-induced endoplasmic reticulum oxidase that regulates translation and folding of oxidized proteins. This study aimed to explore the clinicopathological significance of ERO1A and the effect on the biological behavior of cholangiocarcinoma (CCA) cells. METHODS: Immunohistochemical staining was used to detect the expression of ERO1A, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in cholangiocarcinoma. Immunofluorescence staining was performed to detect the subcellular localization of ERO1A in CCA cells. The expression of ERO1A in CAA cells after depletion or overexpression was verified by Western blot assay. Then, the effect of ERO1A on proliferation in CCA cells was verified by MTT assay and colony formation assay. Wound healing assays and migration assays were performed to detect the effect of ERO1A on cell migration ability. Finally, we explored the role of ERO1A in EMT and Akt/mTOR signaling pathway. RESULTS: In this study, our data demonstrated that ERO1A, CEA, and CA19-9 were expressed in cholangiocarcinoma tissues, and the positive rates were 95%, 95%, and 55%, respectively. The high expression of ERO1A is associated with clinical stage and pathological stage of CCA. In vitro data indicate that deletion of ERO1A can inhibit the proliferation and migration of CCA cells and vice versa. In addition, ERO1A has been shown to be closely related to EMT and Akt/mTOR pathways. CONCLUSION: In summary, we found that high expression of ERO1A is associated with poor prognosis in patients, and ERO1A can promote the proliferation and migration of CCA cells. In conclusion, ERO1A can be used as an independent biomarker for predicting the prognosis of CCA.