ABSTRACT
Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/ß-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.
Subject(s)
Gene Expression Regulation, Neoplastic , Kruppel-Like Factor 4 , Neoplastic Stem Cells , Urinary Bladder Neoplasms , Wnt-5a Protein , Animals , Humans , Mice , beta Catenin/metabolism , beta Catenin/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Kruppel-Like Factor 4/metabolism , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Sp1 Transcription Factor/metabolism , Sp1 Transcription Factor/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Wnt Signaling Pathway/physiology , Wnt Signaling Pathway/genetics , Wnt-5a Protein/metabolism , Wnt-5a Protein/geneticsABSTRACT
BACKGROUND MRT4 Homolog, Ribosome Maturation Factor (MRTO4) is often upregulated in cancer cells. However, its impact in hepatocellular carcinoma (HCC) is less well understood. Herein, we explored the prognostic and energy metabolism reprogramming role of MRTO4 in HCC. MATERIAL AND METHODS Clinical data were obtained from The Cancer Genome Atlas (TCGA), and the expression of MRTO4 in clinical samples was analyzed. The association between different variables and overall survival (OS) was studied, as well as their potential as independent prognostic factors, using Cox regression analysis. We constructed a nomogram including clinical pathological variables and MRTO4 expression to provide a predictive model for prognosis. Heatmaps, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the relationship between energy metabolism pathways and MRTO4. We used classic molecular biology research methods, including RT-qPCR, Western blotting, CCK8, TUNEL, Clone formation, Transwell assay, ELISA, and immunohistochemistry, to study the role of MRTO4 in promoting the progression of HCC through glycolysis regulation. RESULTS Our study showed that MRTO4 is an independent prognostic risk factor for HCC and that MRTO4 accelerates glycolysis of HCC cells, promotes proliferation and invasion, and suppresses apoptosis of HCC cells. The underlying mechanism involves MRTO4 promoting glycolysis and accelerating HCC by inhibiting ALDOB. CONCLUSIONS Our study revealed a novel mechanism by which MRTO4 promotes glycolysis and accelerates HCC progression, and suggests that inhibiting MRTO4 could be a potential therapeutic strategy for HCC.
Subject(s)
Carcinoma, Hepatocellular , Disease Progression , Glycolysis , Liver Neoplasms , Female , Humans , Male , Middle Aged , Apoptosis/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Prognosis , Ribosomal Proteins/metabolism , Ribosomal Proteins/geneticsABSTRACT
The purpose of our study is to examine the correlation between sleep factors and the prevalence of kidney stones in US adults. A total of 34,679 participants from the National Health and Nutrition Examination Survey 2007 to 2018 were included in the analyses. Sleep data collection included: presleep factors (difficulty falling asleep, sleep onset latency), intra-sleep factors (risk index of obstructive sleep apnea, restless leg syndrome, difficulty maintaining sleep), post-sleep factors (daytime sleepiness, non-restorative sleep), sleep schedule and duration, and sleep quality. Logistic regression models were used to analyze the correlation between sleep factors and the prevalence of kidney stones. Among the 34,679 participants, the overall incidence of kidney stones was 9.3%. The presence of presleep factors (difficulty falling asleep [odds ratios [OR], 1.680; 95% CI, 1.310-2.150], prolonged sleep onset latency [OR, 1.320; 95% CI, 1.020-1.700]), intra-sleep factors (higher risk index of obstructive sleep apnea [OR, 1.750; 95% CI, 1.500-2.050], restless leg syndrome [OR, 1.520; 95% CI, 1.150-1.990], difficulty maintaining sleep [OR, 1.430; 95% CI, 1.130-1.810]), post-sleep factors (daytime sleepiness [OR, 1.430; 95% CI, 1.220-1.680], non-restorative sleep [OR, 1.400; 95% CI, 1.110-1.760]), short sleep duration (OR, 1.190; 95% CI, 1.080-1.310), mediate sleep quality (OR, 1.140; 95% CI, 1.020-1.290), and poor sleep quality (OR, 1.500; 95% CI, 1.310-1.720) are linked to the occurrence of kidney stones. However, short sleep onset latency, bedtime and wake-up time were not significantly associated with the prevalence of kidney stones. These findings showed positive associations between higher kidney stone prevalence and poor sleep factors.
Subject(s)
Kidney Calculi , Humans , Male , Kidney Calculi/epidemiology , Female , United States/epidemiology , Middle Aged , Adult , Prevalence , Risk Factors , Nutrition Surveys , Sleep Apnea, Obstructive/epidemiology , Aged , Sleep Wake Disorders/epidemiology , Sleep Quality , IncidenceABSTRACT
Introduction: Redundant robots offer greater flexibility compared to non-redundant ones but are susceptible to increased collision risks when the end-effector approaches the robot's own links. Redundant degrees of freedom (DoFs) present an opportunity for collision avoidance; however, selecting an appropriate inverse kinematics (IK) solution remains challenging due to the infinite possible solutions. Methods: This study proposes a reinforcement learning (RL) enhanced pseudo-inverse approach to address self-collision avoidance in redundant robots. The RL agent is integrated into the redundancy resolution process of a pseudo-inverse method to determine a suitable IK solution for avoiding self-collisions during task execution. Additionally, an improved replay buffer is implemented to enhance the performance of the RL algorithm. Results: Simulations and experiments validate the effectiveness of the proposed method in reducing the risk of self-collision in redundant robots. Conclusion: The RL enhanced pseudo-inverse approach presented in this study demonstrates promising results in mitigating self-collision risks in redundant robots, highlighting its potential for enhancing safety and performance in robotic systems.
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Liver cancer metastasis is the main cause of death in liver cancer patients. Exosomes, which are small vesicles released by cancer cells, play a crucial role in the metastasis of cancer. The aim of this study was to investigate the effect of exosomes derived from high metastatic potential liver cancer cells acting as cell to cell communication on liver cancer metastasis. Bioinformatics analysis was used to obtain the differential expression of exosomal mRNAs from the plasma of both liver cancer patients and healthy volunteers. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and protein blot were employed to characterize the exosomes. The molecular mechanisms and were explored by conducting CCK8, Transwell, Tunel, RTqPCR, western blot, and immunofluorescence staining. We examined IGFBP2 special expression in the plasma exosomes of both liver cancer patients and healthy volunteers, and its presence was associated with a poor prognosis in liver cancer patients. Furthermore, we observed that exosomes from highly metastatic liver cancer cells (MHCC97H) contained high levels of IGFBP2 and could enhance the metastatic potential of less aggressive liver cancer cells (Hep3B). Additionally, we discovered that IGFBP2 in MHCC97H-derived exosomes activated ERK signaling pathway, which triggered epithelial-mesenchymal transition (EMT) in Hep3B cells. Our study underscores the significance of exosomal IGFBP2 from highly metastatic liver cancer cells as a driver of metastasis in less invasive liver cancer cells. This suggests that targeting IGFBP2 in exosomes could be a promising strategy for the treatment and prognosis of liver cancer patients.
Subject(s)
Carcinoma, Hepatocellular , Exosomes , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Exosomes/metabolism , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , MicroRNAs/metabolismABSTRACT
OBJECTIVE: Conventional colonoscopy using a flexible colonoscope remains two major limitations, including patient discomfort and difficult manipulations for surgeons. Robotic colonoscopes have been developed to conduct colonoscopy in a patient-friendly manner. However, most robotic colonoscopes still maintain nonintuitive and difficult manipulations, which limits their clinical applications. In this paper, we demonstrated visual servo-based semi-autonomous manipulations of an electromagnetic actuated soft-tethered (EAST) colonoscope, which aims to lower difficulties of robotic colonoscope manipulations. METHODS: Kinematic modeling of EAST colonoscope is conducted, with an adaptive visual servo controller established. Template matching method and a lumen and polyp detection model are developed to enable semi-autonomous manipulations, including region-of-interest automatic tracking and autonomous navigation with automatic polyp detection. RESULTS: The EAST colonoscope demonstrates visual servoing with an average convergence time of around 2.5 s and performs disturbance rejection within 3.0 s. Semi-autonomous manipulations were conducted in both a commercialized colonoscopy simulator and an ex-vivo porcine colon to show the efficacy of reducing the user workload compared to manual control. CONCLUSION: The EAST colonoscope can perform visual servoing and semi-autonomous manipulations with the developed methods in both laboratory and ex-vivo environments. SIGNIFICANCE: The proposed solutions and techniques improve the autonomy level of robotic colonoscopes and reduce user workloads, which promotes the development and clinical translation of robotic colonoscopy.
Subject(s)
Colonoscopes , Robotics , Swine , Animals , Humans , Equipment Design , Colonoscopy/methods , Colon/diagnostic imagingABSTRACT
Oxidative stress is an important mechanism underlying toxicity induced by cadmium (Cd) exposure. However, there are significant differences of the antioxidant baseline in different populations. This means that different human has different intensity of oxidative stress in vivo after exposure to toxicants. LiasH/H mouse is a specific model which is created by genetically modifying the Lias 3'-untranslated region (3'-UTR). LiasH/H mice express high levels of LA and have high endogenous antioxidant capacity which is approximately 150% higher than wild-type C57BL/6 J mice (WT, Lias+/+). But more importantly, they have dual roles of metal chelator and antioxidant. Here, we applied this mouse model to evaluate the effect of endogenous antioxidant levels in the body on alleviating Cd-induced renal injury including Cd metabolism, oxidative stress, and inflammation. In the experiment, mice drank water containing Cd (50 mg/L), for 12 weeks. Many biomarkers of Cd metabolism, oxidative stress, inflammation, and major pathological changes in the kidney were examined. The results showed overexpression of the Lias gene decreased Cd burden in the body of mice, mitigated oxidative stress, attenuated the inflammatory response, and subsequent alleviated cadmium-induced kidney injury in mice.
ABSTRACT
Bladder cancer is one of the most common malignancies in the urinary system, with high risk of recurrence and progression. However, the difficulty in detecting small tumor lesions and the lack of selectivity of intravesical treatment seriously affect the prognosis of patients with bladder cancer. In the present work, a nanoparticle-based delivery system with tumor targeting, high biocompatibility, simple preparation, and the ability to synergize imaging and therapy was fabricated. Specifically, this nanosystem consisted of the core of doxorubicin (DOX)-loaded polydopamine nanoparticles (PDD NPs) and the shell of hyaluronic acid (HA)-conjugated IR780 (HA-IR780). The HA-IR780-covered PDD NPs (HR-PDD NPs) demonstrated tumor targeting and visualization both in vitro and in vivo with properties of promoted cancer cell endocytosis and lysosomal escape, efficiently delivering drugs to the target site and exerting a killing effect on tumor cells. Encouragingly, intravesical instillation of HR-PDD NPs improved drug retention in the bladder and promoted its accumulation in tumor tissue, resulting in better tumor proliferation inhibition and apoptosis in an orthotopic bladder cancer model in rats. This study provides a promising strategy for the diagnosis and therapy of bladder cancer.
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Implementing industrial policies to develop the new energy vehicle industry and improve technological innovation related to new energy vehicles is essential for countries dealing with environmental pollution and climate change. This paper first examines the impact of a demand-side industry policy related to new energy vehicles on the technological innovation level of supply-side vehicle enterprises. Regarding the new energy vehicle purchase tax exemption policy implemented by the Chinese government in 2014 as a quasi-experiment, this paper constructs a multi-period difference-in-differences (DID) model to identify the impact of the demand-side preferential tax policy on the technological innovation level of vehicle enterprises. In our DID design, 178 enterprises are in the treatment group and 166 enterprises in the control group, with 3,440 balanced panel data of observations. The results show that this policy can significantly promote the technological innovation of new energy vehicle enterprises. This promotion effect is greater in magnitude in large-scale enterprises, high-tech enterprises, and enterprises producing passenger vehicles. Theoretically, we believe that the demand-side tax exemption policy mainly indirectly promotes the technological innovation level of automobile enterprises through the signal channel and profit channel.
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The behavior of heavy metals in contaminated sediment is of ecological significance considering the change of pH caused by ocean acidification. This study investigated the mobility of Cd, Cu, Ni, Pb, Fe, and Mn under experimental conditions for seawater acidification via enrichment of CO2 gas at different reaction set-ups. The results indicated that the concerned metals behaved differently in the water compared to the sediment. The heavy metals were considerably transferred from sediment to seawater, and the resultant intensity was controlled by the degree of acidification and the chemical state of specific metals. Moreover, labile fractions of heavy metals in sediments were more susceptible to acidification than other fractions. These findings were observed and confirmed using real-time monitoring conducted via the diffusion gradient technique (DGT). Overall, the results of this study provided new insights into exploring the coupling risk of heavy metals with ocean acidification.
Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Seawater , Geologic Sediments , Ocean Acidification , Hydrogen-Ion Concentration , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring/methodsABSTRACT
Time-variant quadratic programming (QP) with multi-type constraints including equality, inequality, and bound constraints is ubiquitous in practice. In the literature, there exist a few zeroing neural networks (ZNNs) that are applicable to time-variant QPs with multi-type constraints. These ZNN solvers involve continuous and differentiable elements for handling inequality and/or bound constraints, and they possess their own drawbacks such as the failure in solving problems, the approximated optimal solutions, and the boring and sometimes difficult process of tuning parameters. Differing from the existing ZNN solvers, this article aims to propose a novel ZNN solver for time-variant QPs with multi-type constraints based on a continuous but not differentiable projection operator that is deemed unsuitable for designing ZNN solvers in the community, due to the lack of the required time derivative information. To achieve the aforementioned aim, the upper right-hand Dini derivative of the projection operator with respect to its input is introduced to serve as a mode switcher, leading to a novel ZNN solver, termed Dini-derivative-aided ZNN (Dini-ZNN). In theory, the convergent optimal solution of the Dini-ZNN solver is rigorously analyzed and proved. Comparative validations are performed, verifying the effectiveness of the Dini-ZNN solver that has merits such as guaranteed capability to solve problems, high solution accuracy, and no extra hyperparameter to be tuned. To illustrate potential applications, the Dini-ZNN solver is successfully applied to kinematic control of a joint-constrained robot with simulation and experimentation conducted.
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PURPOSE: To explore an efficient preventive strategy for radiation cystitis. METHODS: We instilled IR-780 into the bladders of rats 1 h before bladder irradiation, and its bio-distribution was observed at different times. Bladders were then examined for pathogenic alterations and inflammation levels by day 3 and week 12 postirradiation, and the functional characteristics of the bladder were tested via cystometry by week 12. Human uroepithelial sv-huc-1 cells were used to determine the effect of IR-780 on cell viability, regardless of irradiation. We measured the intracellular levels of oxidative stress, DNA damage, apoptosis proportion, and the expression of antioxidant proteases and apoptotic caspases in IR-780 pretreated cells after radiation. RESULTS: IR-780 is localized in the urothelium after intravesical instillation in vivo. Ionizing radiation could induce acute impairment of the bladder urothelium and inflammation in the bladder on day 3. Fibrosis of the irradiated bladder progressed and eventually affected voiding function at 12 weeks. Treatment with IR-780 before irradiation ameliorated these changes. In vitro, IR-780 protected against cell viability and apoptosis of sv-huc-1 cells after irradiation. Additionally, IR-780 may assist in eliminating reactive oxygen species and repairing irradiation-induced DNA damage. CONCLUSION: Our data indicate that IR-780 can be used before irradiation to prevent acute urinary mucosal injury and late bladder dysfunction. Moreover, early urothelial impairment plays a significant role in radiation cystitis development.
Subject(s)
Cystitis , Radiation Injuries , Rats , Animals , Humans , Administration, Intravesical , Urothelium/metabolism , Cystitis/prevention & control , Cystitis/chemically induced , Inflammation/metabolism , Radiation Injuries/prevention & controlABSTRACT
BACKGROUND: Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. MATERIAL AND METHODS: The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. RESULTS: IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. CONCLUSION: We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.
Subject(s)
Hyperbaric Oxygenation , Radiation-Sensitizing Agents , Urinary Bladder Neoplasms , Humans , Animals , Mice , Reactive Oxygen Species/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/metabolism , Apoptosis , Radiation-Sensitizing Agents/pharmacology , Mitochondria , Cell Line, TumorABSTRACT
Generally, the infinity-norm joint-velocity minimization (INVM) of physically constrained kinematically redundant robots can be formulated as time-variant linear programming (TVLP) with equality and inequality constraints. Zeroing neural network (ZNN) is an effective neural method for solving equality-constrained TVLP. For inequality-constrained TVLP, however, existing ZNNs become incompetent due to the lack of relevant derivative information and the inability to handle inequality constraints. Currently, there is no capable ZNN in the literature that has achieved the INVM of redundant robots under joint limits. To fill this gap, a classical INVM scheme is first introduced in this article. Then, a new joint-limit handling technique is proposed and employed to convert the INVM scheme into a unified TVLP with full derivative information. By using a perturbed Fisher-Burmeister function, the TVLP is further converted into a nonlinear equation. These conversion techniques lay a foundation for the success of designing a capable ZNN. To solve the nonlinear equation and the TVLP, a novel continuous-time ZNN (CTZNN) is designed and its corresponding discrete-time ZNN (DTZNN) is established using an extrapolated backward differentiation formula. Theoretical analysis is rigorously conducted to prove the convergence of the neural approach. Numerical studies are performed by comparing the DTZNN solver and the state-of-the-art (SOTA) linear programming (LP) solvers. Comparative results show that the DTZNN consumes the least computing time and can be a powerful alternative to the SOTA solvers. The DTZNN and the INVM scheme are finally applied to control two kinematically redundant robots. Both simulative and experimental results show that the robots successfully accomplish user-specified path-tracking tasks, verifying the effectiveness and practicability of the proposed neural approach and the INVM scheme equipped with the new joint-limit handling technique.
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Clinical management of cyclophosphamide (CYP) results in numerous side effects including hemorrhagic cystitis (HC), which is characterized by inflammation and oxidative stress damage. Intravesical hyaluronic acid (HA) supplementation, a therapeutic method to restore barrier function of bladder, avoid the stimulation of metabolic toxicants on bladder and reduce inflammatory response, has shown good results in acute or chronic bladder diseases. However, there are unmet medical needs for the treatment of HC to temporarily restore bladder barrier and reduce inflammation. Herein, sulfhydryl functionalized HA (HA-SH) and dimethyl sulfoxide (DMSO) were used to prepared a hydrogel system for optimizing the treatment of HC. We systematically evaluated the physicochemical of hydrogels and their roles in a rat model of CYP-induced HC. The prepared hydrogels exhibited outstanding gel forming properties, injectability, and biosafety. Swelling and retention studies showed that hydrogels were stable and could prolong the residence time of HA in the bladder. Histopathology and vascular permeability studies indicated that the hydrogels significantly attenuated bladder injury caused by CYP administration. Moreover, the hydrogels also showed excellent anti-inflammation and anti-oxidation properties. In conclusion, these data suggest that intravesical instillation of HA-SH/DMSO hydrogels reduces CYP-induced bladder toxicity and this work provides a new strategy for the prevention and early treatment of HC.
Subject(s)
Cystitis , Urinary Bladder , Rats , Animals , Hyaluronic Acid/pharmacology , Hydrogels/pharmacology , Dimethyl Sulfoxide , Cystitis/chemically induced , Cystitis/drug therapy , Cystitis/metabolism , Cyclophosphamide/adverse effects , Hemorrhage , Inflammation/metabolismABSTRACT
Manual rigid endoscopes have defects such as a low efficiency, difficult operation, and safety risks, and the antinoise interference ability, convergence speed, and control accuracy of the neural network control technology for the existing autonomous endoscopes are often ignored. Solving these problems is important for the stable operation of endoscopes. Therefore, a new adaptive fast convergent antinoise dual neural network (AFA-DNN) controller for the visual servo control of ten-degree of freedom flexible endoscope robots (FERs) with physical constraints is proposed in this work. First, the control scheme of the FERs is formulated as a quadratic programming problem, and then, an AFA-DNN visual servo controller is designed for the FERs. The adaptive gains of the controller can accelerate the convergence, improve the antinoise ability, and increase the convergence accuracy of the controller. Then, according to the Lyapunov theory, the fast convergence of the AFA-DNN in finite time is proven for both noise-free and noisy conditions. The experimental results indicate that the FER controlled by the proposed AFA-DNN can accurately track various trajectories and that the AFA-DNN has a better antinoise interference ability, higher convergence accuracy, and faster convergence speed than conventional methods. The convergence speed of the AFA-DNN is increased by a factor of 4.22 by using the adaptive gains. Experiments also indicate that the AFA-DNN remains well functioning under various noise disturbances (such as constant, periodic, linear, and Gaussian noise).
ABSTRACT
As a representative of immiscible alloy systems, the Cu-Ta system was the research topic because of its potential application in industry, military and defense fields. In this study, an amorphous Cu-Ta alloy film was manufactured through magnetron sputter deposition, which was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Mechanical properties of Cu-Ta film were detected by the nanoindentation method, which show that the elastic modulus of Cu3.5Ta96.5 is 156.7 GPa, and the hardness is 14.4 GPa. The nanoindentation process was also simulated by molecular dynamic simulation to indicate the deformation mechanism during the load-unload stage. The simulation results show that the structure <0,2,8,4> and <0,2,8,5> Voronoi cells decreased by 0.1% at 50 Ps and then remained at this value during the nanoindentation process. In addition, the number of dislocations vary rapidly with the depth between indenter and surface. Based on the experimental and simulation results, the Voronoi structural changes and dislocation motions are the key reasons for the crystallization of amorphous alloys when loads are applied.
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Gastric cancer (GC) is one of the most common malignancies, ranking the third highest mortality rate worldwide. Due to the insidious symptoms and difficulty in early detection, patients with GS were mostly in the middle and late stages when they were diagnosed. Although ontogenetic or tumor-suppressive effects of miRNA-200a-3p have been demonstrated, the exact mechanism underlying GC is not clear. Therefore, the expression, effect, and mechanism of miRNA-200a-3p in GC progression were systematically investigated in this study. qRT-PCR, Western blotting, and immunohistochemical staining were applied to investigate the miRNA-200a-3p and deleted in liver cancer 1 (DLC-1) expression. Cell viability, proliferation, apoptosis, migration, and invasion capabilities of GC cells were assessed using cell counting kit-8 (CCK-8) colorimetry, EdU integration, flow cytometry, wound healing, and the transwell assay. The relationship between miRNA-200a-3p and tumor growth was investigated by tumor xenograft assay in vivo. A dual-luciferase reporter assay was estimated to verify the connection between miR-200-3p and DLC-1. The results showed that miRNA-200a-3p expression was significantly increased in both GC tissues and cells. Furthermore, via DLC-1, miRNA-200a-3p promotes tumor growth and development. miRNA-200a-3p, by targeting DLC-1, can function as an oncogene in GC cells. Collectively, our findings indicated that the miRNA-200a-3p/DLC axis might provide a theological basis for potential improvements in GC treatment strategies.
Subject(s)
Gene Expression Regulation, Neoplastic/physiology , MicroRNAs/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Animals , Apoptosis , Blotting, Western , Cell Count , Cell Movement , Cell Proliferation , Cell Survival , Disease Progression , Female , Gene Targeting , Humans , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Real-Time Polymerase Chain Reaction , Stomach Neoplasms/pathology , Transfection , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Background: Colorectal cancer (CRC) is the third most common malignancy worldwide. Matrine can act as a potential antitumor drug, and its antitumor activities have been tested in various cancers, including CRC. However, the effect of matrine and the related mechanisms on CRC cells remains poorly defined. Materials and Methods: CRC cells were treated with different concentrations of matrine, and then MTT, flow cytometric, and transwell assays were used to assess cell proliferation, apoptosis, invasion, and migration. MiR-10b-5p and Phosphatase and tensin homolog (PTEN) expression levels were measured by quantitative real-time polymerase chain reaction and Western blot assay. The binding interaction of miR-10b-5p and PTEN were predicted by TargetScan and verified by a dual-luciferase reporter and RIP assay. The effect of matrine, miR-10b-5p, and PTEN on CRC cell proliferation, apoptosis, migration, and invasion was detected by MTT, flow cytometric, and transwell assays severally. Results: Matrine notably restrained proliferation, invasion, and migration and boosted apoptosis of CRC cells, as well as downregulated miR-10b-5p expression and upregulated PTEN protein level. PTEN was a direct target of miR-10b-5p in CRC cells. MiR-10b-5p knockdown and matrine treatment inhibited cell proliferation, migration, and invasion and induced apoptosis, and reintroduction of si-PTEN partly regained the inhibiting effect. Besides, MiR-10b-5p knockdown and matrine treatment repressed CRC growth in vivo. Conclusion: Matrine could suppress proliferation, migration, and invasion and induce apoptosis of CRC cells via the miR-10b/PTEN pathway, providing the potential molecular mechanism of matrine in blocking CRC progression.
Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , PTEN Phosphohydrolase/genetics , Matrines , Neoplasm Invasiveness , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Movement , Apoptosis , Cell Proliferation , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, NeoplasticABSTRACT
This study aimed at elucidating some characteristics of the shock wave overpressure generated by a non-traditional layered charge comprising an inner high-energy explosive and an outer polymer matrix composite. Two models for predicting the peak overpressure (Δpm) of the charge were established, namely, a model based on the initial parameters of the blast wave, and a model considering the weakening of the explosion energy through the introduction of polymer matrix cladding. The overpressure of a typical layered charge was experimentally measured for model validation. It was found that the difference between the Δpm predicted by the two models and the experimental data is less than 15.12% and 14.17%, respectively. The model that was established based on the conservation of energy law, is in best agreement with the experimental data under different cladding/charge mass ratios (αm). The model that was based on the initial parameters of the blast wave obtained a low predicted value when αm was 0.4-0.8, which is attributed to the non-uniformity of the gas-solid mixture during the explosive dispersion stage.