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CoCrNi medium-entropy alloys (MEAs) have attracted extensive attention and research because of their superior mechanical properties, such as higher ductility, strength, and toughness. This study uses molecular dynamics (MD) simulations to investigate the cutting behavior of a gradient nanograined (GNG) CoCrNi MEA. Moreover, it explores the influence of relative tool sharpness and rake angle on the cutting process. The results show that an increase in the average grain size of the GNG samples leads to a decrease in the average resultant cutting force, as predicted by the Hall-Petch relationship. The deformation behavior shows that grain boundaries are crucial in inhibiting the propagation of strain and stress. As the average grain size of the GNG sample increases, the range of shear strain distribution and average von Mises stress decreases. Moreover, the cutting chips become thinner and longer. The subsurface damage is limited to a shallow layer at the surface. Since thermal energy is generated in the high grain boundary density, the temperature of the contact zone between the substrate and the cutting tool increases as the GNG size decreases. The cutting chips removed from the GNG CoCrNi MEA substrates will transform into a mixed structure of face-centered cubic and hexagonally close-packed phases. The sliding and twisting of grain boundaries and the merging of grains are essential mechanisms for polycrystalline deformation. Regarding the cutting parameters, the average resultant force, the material accumulation, and the chip volume increase significantly with the increase in cutting depth. In contrast to sharp tools, which mainly use shear deformation, blunt tools remove material by plowing, and the cutting force increases with the increase in cutting-edge radius and negative rake angle.
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As a sort of fluorescent carbon nanomaterial with a particle size of less than 10 nm, carbon dots (CDs) have their own merits of good dispersibility in water, stable optical properties, strong chemical inertness, stable optical properties, and good biosecurity. These excellent peculiarities facilitated them like sensing, imaging, medicine, catalysis, and optoelectronics, making them a new star in the field of nanotechnology. In particular, the development of CDs in the fields of chemical probes, imaging, cancer therapy, antibacterial and drug delivery has become a hot topic in current research. Although the biomedical applications in CDs have been demonstrated in many research articles, a systematic summary of their role in biomedical applications is scarce. In this review, we introduced the basic information of CDs in detail, including synthesis approaches of CDs as well as their favorable properties including photoluminescence and low cytotoxicity. Subsequently, the application of CDs in the field of biomedicine was emphasized. Finally, the main challenges and research prospects of CDs in this field were proposed, which might provide some detailed information in designing new CDs in this promising biomedical field.
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Carbono , Puntos Cuánticos , Carbono/química , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Humanos , AnimalesRESUMEN
The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe3+ LA NPs by HepG2 cells. Meanwhile, Fe3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (·OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System Xc-), which promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metal-coordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy.
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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Neoplasias , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Preparaciones Farmacéuticas , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Combinada , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Tomato cultivars with contrasting resistance to pathogens regulate root exudates differentially in response to Ralstonia solanacearum attacks. However, strategies using innate root exudates against infection remain unknown. This study analyzed the innate root exudates of two tomato cultivars and their functions in regulating R. solanacearum infection. The innate root exudates differed between the two cultivars. Astaxanthin released from resistant plants inhibited colonization by R. solanacearum but promoted motility, while neferine released from susceptible plants suppressed motility and colonization. The secretion of astaxanthin in resistant tomatoes promoted the growth of biocontrol fungi in soil and reduced the abundance of pathogenic fungi. Neferine secreted by the susceptible cultivar inhibited the relative abundance of the bacterial-biocontrol-related Bacillus genus, indirectly reducing the soil's immune capacity. This study revealed contrasting strategies using root exudates in resistant and susceptible tomato cultivars to cope with R. solanacearum infection, providing a basis for breeding disease-resistant cultivars.
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Ralstonia solanacearum , Solanum lycopersicum , Habilidades de Afrontamiento , Fitomejoramiento , Suelo , Enfermedades de las Plantas/microbiologíaRESUMEN
PURPOSE: To delineate the 10 years' trend regarding Taiwanese adolescents' health perspectives and compare the differences of six adolescent health aspects between Taiwan and the U.S. METHODS: The anonymous structured questionnaire was done every other year with representative sampling methods as Youth Risk Behavior Surveillance System in the United States. Twenty-one questions from six health aspects were extracted for further analysis. Multivariate regression analysis was performed to delineate the relationship among protective factors and risk-taking behaviors, respectively. RESULTS: Overall, 22,419 adolescents were recruited. There were decreasing trend in terms of risk-taking behaviors, such as early contact to pornography (< age 16) (70.6%-60.9%), early cigarette use (< age 13) (20.7%-14.0%), and seriously considering suicide (36.0%-17.8%). There was an increasing trend in behaviors harmful to health: current alcohol drinkers (18.9%-23.4%), and staying up late every day (15.2%-18.5%). Multivariate regression analysis after adjusting gender and grade; it disclosed an increasing trend in protective assets, such as having multiple intimate friends (75.8%-79.3%), satisfaction to body weight and body shape (31.5%-36.1% and 34.5%-40.7%), as well as always wearing a helmet while riding a bike (1.8%-3.0%). CONCLUSION: We should continuously monitor the health status trend of the adolescents to provide them with a healthier environment and well-being.
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Conducta del Adolescente , Humanos , Adolescente , Estados Unidos , Conductas Relacionadas con la Salud , Conducta Sexual , Asunción de Riesgos , EstudiantesRESUMEN
Acute kidney injury (AKI) is a common syndrome characterized by various etiologies and pathophysiologic processes that deteriorate kidney function. The aim of this study is to identify potential biomarkers in the urine of non-acute kidney injury (non-AKI) and AKI patients through Raman spectroscopy (RS) to predict the advancement in complications and kidney failure. Selected spectral regions containing prominent peaks of renal biomarkers were subjected to partial least squares linear discriminant analysis (PLS-LDA). This discriminant analysis classified the AKI patients from non-AKI subjects with a sensitivity and specificity of 97% and 100%, respectively. In this study, the RS measurements of urine specimens demonstrated that AKI had significantly higher nitrogenous compounds, porphyrin, tryptophan and neopterin when compared with non-AKI. This study's specific spectral information can be used to design an in vivo RS approach for the detection of AKI diseases.
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Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.
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Anticoagulantes/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Ginsenósidos/farmacología , Interacciones de Hierba-Droga/fisiología , Warfarina/farmacología , Animales , Coagulación Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/metabolismo , Línea Celular , Sistema Enzimático del Citocromo P-450/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Panax/química , Extractos Vegetales/farmacología , Ratas , Trombosis/tratamiento farmacológico , Trombosis/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
We report on a novel method for saliva identification by reverse transcription-loop-mediated isothermal amplification (RT-LAMP). In our previous report, real-time RT-LAMP was used for blood identification by using HBB detection as a model but in this advanced study, this method was refined for the identification of the more challenging body fluid of saliva. Expression of the18S rRNA gene was used as the internal control and the Statherin (STATH) gene as the saliva-specific marker. A turbidimeter was used for real-time detection of the RT-LAMP products, and confirmation was obtained that the real products were generated using: agarose gel electrophoresis, calcein fluorescence detection and/or enzymatic digestion. The specificity of the test was performed using 42 samples including 7 different body fluids, and the expression of STATH was only observed in all the saliva samples (6) with a threshold time of 39.4 ± 2.9 min. Sensitivity testing showed that RT-LAMP products for STATH were stably detected when the RNA template was not less than 6.25 ng. When the primer concentrations for STATH were two times that of 18S rRNA, saliva could be identified in the body fluid mixtures even at a ratio (saliva:semen) of 1:3 (without loop primer)/1:5 (with loop primer). A multiplex RT-LAMP was established to simultaneously amplify the 18S rRNA and STATH genes, and applied to the identification of saliva on ten non-probative cigarette butts. A positive result for saliva was obtained from all ten butts, even for those that returned a negative or ambiguous result using the amylase test. A direct RT-LAMP test is also reported where the RNA extraction step was omitted to speed the collection of data and all tests using either the simplex or multiplex RT-LAMP resulted in a positive response if saliva was present. Our data provide a simple and effective means to detect the presence of saliva.
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Técnicas de Amplificación de Ácido Nucleico/métodos , Saliva/química , Amilasas/análisis , Biomarcadores/análisis , Medicina Legal/métodos , Marcadores Genéticos , Humanos , ARN Ribosómico 18S/metabolismo , Proteínas y Péptidos Salivales/genética , Sensibilidad y EspecificidadRESUMEN
While glycolate oxidase (GLO) is well known as a key enzyme for the photorespiratory metabolism in plants, its physiological function and mechanism remains to be further clarified. Our previous studies have shown that suppression of GLO in rice leads to stunted growth and inhibited photosynthesis (Pn) which is positively and linearly correlated with decreased GLO activities. It is, therefore, of interest to further understand whether Pn can be improved when GLO is up-regulated? In this study, four independent overexpression rice lines, with gradient increases in GLO activity, were generated and functionally analyzed. Phenotypic observations showed that the growth could be improved when GLO activities were increased by 60 or 100%, whereas reduced growth was noticed when the activity was further increased by 150 or 210%. As compared with WT plants, all the overexpression plants exhibited significantly improved Pn under conditions of high light and high temperature, but not under normal conditions. In addition, the overexpression plants were more resistant to the MV-induced photooxidative stress. It was further demonstrated that the antioxidant enzymes, and the antioxidant metabolite glutathione was not significantly altered in the overexpression plants. In contrast, H2O2 and salicylic acid (SA) were correspondingly induced upon the GLO overexpression. Taken together, the results suggest that GLO may play an important role for plants to cope with high light and high temperature, and that H2O2 and SA may serve as signaling molecules to trigger stress defense responses but antioxidant reactions appear not to be involved in the defense.
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This paper presents a dynamically compensated velocity observer (DCVO), in which acceleration measurement is employed to estimate velocity. Its sensitivity to the noise that is associated with the acceleration measurement is formulated and compared with that of a conventional state-space velocity observer (SSVO). Unlike the SSVO, the DCVO is completely insensitive to an accelerometer offset. The DCVO, the SSVO and a common ITM-based estimator are all realized in a linear motion stage, to determine their effectiveness. A sliding-mode controller is also implemented with different velocity observers, and it is shown that the DCVO enables high-frequency switching of the sliding-mode controller and also practically improves the positioning accuracy.
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This paper proposes a sliding-mode repetitive learning control (SMRLC) scheme with an integral sliding-mode perturbation observer (ISMPO) for repetitive tracking control tasks. The three control strategies which are synthesized to yield excellent tracking performance are: (1) the pole-placement feedback control to specify the desired error dynamics; (2) ISMPO-based feedback compensation as the robust part; and (3) a feedforward learning component that refines the control to improve system performance through repetitive trials. The ISMPO-based feedback compensation ensures that there is only small tracking error during initial learning trials and enhances system insensitivity to exceptional and aperiodic disturbances. The feedforward learning compensation is updated according to a certain switching signal that is equivalent to the compensation error of the feedforward control, yielding fast convergence of the learning process from trial to trial. Experimental results demonstrate the feasibility of the proposed scheme.