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In ßthalassemia, excessive αglobin chain impedes the normal development of red blood cells resulting in anemia. Numerous miRNAs, including miR67473p, are aberrantly expressed in ßthalassemia major (ßTM), but there are no reports on the mechanism of miR67473p in regulating red blood cell lineage development and fetal hemoglobin (HbF) expression. In the present study, RTqPCR was utilized to confirm miR67473p expression in patients with ßTM and the healthy controls. Electrotransfection was employed to introduce the miR67473p mimic and inhibitor in both HUDEP2 and K562 cells, and red blood cell lineage development was evaluated by CCK8 assay, flow cytometry, WrightGiemsa staining and Benzidine blue staining. Bcell lymphoma/leukemia 11A (BCL11A) was selected as a candidate target gene of miR67473p for further validation through FISH assay, dual luciferase assay and Western blotting. The results indicated that miR67473p expression was notably higher in patients with ßTM compared with healthy controls and was positively related to HbF levels. Functionally, miR67473p overexpression resulted in the hindrance of cell proliferation, promotion of cell apoptosis, facilitation of cellular erythroid differentiation and γglobin expression in HUDEP2 and K562 cells. Mechanistically, miR67473p could specifically bind to the 546552 loci of BCL11A 3'UTR and induce γglobin expression. These data indicate that upregulation of miR67473p affects red blood cell lineage development and induces HbF expression by targeting BCL11A in ßthalassemia, highlighting miR67473p as a potential molecular target for ßthalassemia therapy.
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Hemoglobina Fetal , MicroARNs , Proteínas Represoras , Talasemia beta , Humanos , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Talasemia beta/genética , Talasemia beta/metabolismo , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Células K562 , Masculino , Femenino , Eritrocitos/metabolismo , Linaje de la Célula/genética , Regulación hacia Arriba , Apoptosis/genética , Adulto , Proliferación Celular/genética , Regulación de la Expresión Génica , Regiones no Traducidas 3' , Diferenciación Celular/genética , AdolescenteRESUMEN
Purpose: The purpose of this study was to investigate the short- and long-term learning effect of dynamic visual acuity (DVA) tests. Methods: Participants between 18 and 30 years with corrected to normal visual acuity were enrolled in this study. Three repeated sessions were performed, with 15 minutes and 15 days' intervals between sessions. Each session included 9 DVA tests of horizontal, vertical, and diagonal motions of E optotypes at 20, 40, and 80 degrees per second (dps). The short- and long-term learning effects were analyzed from repeated DVA tests. Results: Of the 58 enrolled participants, the mean age was 23.1 ± 2.1 years. DVA significantly varied among motion types and velocities (P < 0.05, respectively). There was a significant short-term learning effect for 20 (P = 0.004), 40 (P < 0.001), and 80 (P = 0.014) dps DVA test of horizontal motion, 40 dps DVA test of vertical (P = 0.003), and diagonal motion (P = 0.036). The long-term learning effect was detected in the 40 dps diagonal motion DVA test (P = 0.015). The short- and long-term learning effects were positively associated with initial DVA in most combinations of motion type and velocity tests (P < 0.05, respectively). The short- (P = 0.031) and long-term (P = 0.024) learning effect of 80 dps horizontal motion DVA test was greater in male than female participants. Conclusions: There is a significant short-term learning effect in the DVA test of various motion types, but the long-term learning effect was rarely observed, and it is greater in participants with worse initial DVA.
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Pruebas de Visión , Agudeza Visual , Humanos , Masculino , Agudeza Visual/fisiología , Femenino , Adulto , Adulto Joven , Adolescente , Aprendizaje/fisiología , Factores de Tiempo , Percepción de Movimiento/fisiologíaRESUMEN
This study presents a design of a 3D interface simulation model featuring an inverted pyramid structure. Our objective is to forecast the performance of GaN-based betavoltaic nuclear batteries with the PN junction 3D interface structures comparing a practical machining process. Initially, we computed the electron-hole pairs (EHPs) generation rate in GaN materials irradiated by both 63Ni and 147Pm sources using Geant4. Furthermore, we employed COMSOL Multiphysics, a finite element analysis software, to simulate the EHPs transport phenomena within the battery and investigate the influence of structural parameters on the output performance. Despite maintaining thicknesses of the P- and N-regions and consistent doping concentrations (Hp-GaN, Hn-GaN, Na, and Nd) as constants, the simulation results revealed notable disparities in the short-circuit current density (Jsc), open-circuit voltage (Voc), and maximum output power density (Pmax) among batteries irradiated with various radioactive sources. Subsequently, we investigated the output performance of the nuclear battery by altering parameters such as the number of inverted pyramid structures, junction depth, and type of radioactive source. Our investigation revealed that selecting 63Ni as the radioactive source, with Na at 1017 cm-3, Nd at 1014 cm-3, a junction depth of 0.1 µm, and inverted pyramid structures of 25, resulted in the following battery performance parameters: a short-circuit current density (Jsc) of 0.648 µA/cm2, an open-circuit voltage (Voc) of 2.3481 V, and a maximum output power density (Pmax) of 1.2949 µW/cm2. Substituting the radioactive source with 147Pm, the average short-circuit current density, Jsc, increased to 56.865 µA/cm2, and the maximum output power density, Pmax, increased to 94.975 µW/cm2, It's a significant enhancement in output performance.
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Verticillium dahliae is a widespread and destructive soilborne fungus that can cause vascular wilt disease and substantially reduce cotton (Gossypium hirsutum) yield and quality. Scopoletin, a natural coumarin, exhibits antifungal activity against V. dahliae; however, the mechanisms of action remain unclear. In this study, we reveal the regulatory activities of feruloyl-CoA 6'-hydroxylase 1 (GhF6'H1) in enhancing V. dahliae resistance by modulating scopoletin accumulation. Silencing GhF6'H1, encoding the pivotal enzyme in scopoletin biosynthesis, through virus-induced silencing resulted in increased susceptibility to V. dahliae and decreased scopoletin accumulation. In transgenic cotton plants expressing GhF6'H1 under the CaMV 35S promoter, GhF6'H1 modulated scopoletin accumulation, affecting cotton resistance to V. dahliae, with increased resistance associated with increased scopoletin accumulation. GhF6'H1 has been identified as a direct target of the transcription factor GhWRKY33-like, indicating that GhWRKY33-like can bind to and activate the GhF6'H1 promoter. Moreover, GhWRKY33-like overexpression in cotton enhanced resistance to V. dahliae through scopoletin accumulation, phenylpropanoid pathway activation, and upregulation of defense response genes. Ectopic expression of GhF6'H1 resulted in effective catalysis of scopoletin synthesis in enzyme assays using substrates like feruloyl coenzyme A, while molecular docking analysis revealed specific amino acid residues playing crucial roles in establishing salt-bridge interactions with the substrate. These findings suggest that GhF6`H1, regulated by GhWRKY33-like, plays a crucial role in enhancing cotton resistance to V. dahliae by modulating scopoletin accumulation.
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Pancreatic ductal adenocarcinoma (PDAC) relies heavily on neoangiogenesis for its progression, making early detection crucial. Here, LTZi-MHI148 (Letrozole inhibitor bonding with MHI-148 dye), a near-infrared (NIR) fluorescent agent is developed, to target RhoJ (Ras Homolog Family Member J), a protein expressed in neonatal vasculature, for both imaging and therapy of early PDAC. This agent is synthesized by conjugating Letrozole with MHI-148, exhibiting excellent NIR characteristics and photostability. In vitro studies showed that LTZi-MHI148 selectively accumulated within pancreatic cancer cells through Organic Anion Transporting Polypeptide (OATP) transporters and bound to cytoplasmic RhoJ. In vivo, the probe effectively targeted neoangiogenesis and Pancreatic Intraepithelial Neoplasias (PanINs) in various PDAC models, including the orthotopic, ectopic, spontaneous, and tamoxifen-induced tumors. Notably, LTZi-MHI148 detected preneoplastic PanIN lesions with Overexpressed RhoJ and active neoangiogenesis in both spontaneous and tamoxifen-induced PDAC murine models. Longitudinal imaging studies revealed that RhoJ-targeted neoangiogenesis tracks lesion progression, highlighting LTZi-MHI148's utility in monitoring disease progression. Furthermore, multiple LTZi-MHI148 administrations attenuated PanINs to PDAC progression, suggesting its potential as a therapeutic intervention. These findings underscore the translational potential of LTZi-MHI148 for the early detection and targeted therapy of PDAC, utilizing NIR-I/II imaging to monitor RhoJ overexpression in precancerous ductal neoplasia associated with neoangiogenesis.
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The oxygen level in the tumor microenvironment (TME) plays a critical role in regulating cell fates such as proliferation, migration, apoptosis, and so forth. To better elucidate how hypoxia affects tumor cell behaviors, a series of microfluidic strategies have been utilized to generate an oxygen gradient covering both hypoxia and normoxia conditions. However, in most studies, some chemicals are introduced into microfluidic chips, causing the potential of their poor biocompatibility. The common oxygen gradient with linear variation does not allow the effects of specific oxygen concentrations on tumor cells to be analyzed accurately. In this paper, based on the physical method of gas diffusion, a microfluidic device integrated with an oxygen gradient generator is proposed for investigating effects of different hypoxia levels on responses of tumor cells. This device consists of three layers, i.e., upper layer, thin film layer, and bottom layer. The upper layer is used for introducing the initial gas and generating an oxygen gradient in the form of gas. The bottom layer is used for introducing cells and culture medium. The thin film layer separates the former two layers, allowing the gas to diffuse from the top to the bottom through it. The oxygen gradient in the bottom layer is finally generated in the form of dissolved oxygen. The device is fabricated using microfabrication technology. The effects of structural and working parameters of the device on the oxygen gradient are evaluated by finite element simulation. The oxygen gradient in cell culture channels is characterized by using oxygen-sensitive fluorescence materials. The proliferation and morphology of HeLa cells under specific oxygen levels are compared after culturing for 48 h. The oxygen gradient with a ladder-like distribution demonstrates that this microfluidic device can provide a prospective experimental platform for in vitro cell studies and revelation of the mechanism of tumor metastasis associated with a specific hypoxic microenvironment.
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Oxígeno , Humanos , Oxígeno/química , Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas/instrumentación , Células HeLa , Microambiente Tumoral , Hipoxia de la CélulaRESUMEN
Purpose: Thalassemia, an inherited quantitative globin disorder, is the most prevalent monogenic disease globally. While severe alpha thalassemia results in intrauterine death, ß-thalassemia manifests during childhood due to the "second conversion of hemoglobin", garnering increased attention in recent decades. Methods: In this study, a bibliometric analysis was conducted of thalassemia articles published in the Web of Science Core Collection database between 2013 and 2023 to establish a comprehensive overview and to identify emerging trends. A total of 5655 studies published between 2013 and 2023 were systematically retrieved, and annual publications demonstrated a steady increase, maintaining a high level over the past decade. Results: The United States contributed the highest number of publications, followed by China. Notably, the journal Blood emerged as the leading authority in ß-thalassemia research. Analysis of research hotspots revealed that the pathogenesis of ß-thalassemia is primarily linked to iron overload, anemia, gene mutations, and ineffective erythropoiesis. Furthermore, recent studies focusing on gene editing therapies present promising avenues for future investigation. Conclusion: These findings grasp the research status of ß-thalassemia and shed new light on future research frontiers.
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Chitin-degrading enzymes are critical components in regulating the molting process of the Asian corn borer and serve as potential targets for controlling this destructive pest of maize. Here, we used a scaffold-hopping strategy to design a series of efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition of chitinase from OfChi-h and OfChtI at low nanomolar concentrations (IC50 = 1.51 and 9.21 nM, respectively). Molecular docking simulations suggested that 8c binds to chitinase by mimicking the interaction of chitin oligosaccharide substrates with chitinase. At low ppm concentrations, compound 8c performed comparably to commercial insecticides in controlling the highly destructive plant pest, the Asian corn borer. Tests on a wide range of nontarget organisms indicate that compound 8c has very low toxicity. In addition, the effect of inhibitor treatment on the expression of genes associated with the Asian corn borer chitin-degrading enzymes was further investigated by quantitative real-time polymerase chain reaction. In conclusion, our study highlights the potential of 8c as a novel chitinase-targeting insecticide for effective control of the Asian corn borer, providing a promising solution in the quest for sustainable pest management.
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Quitina , Quitinasas , Proteínas de Insectos , Insecticidas , Simulación del Acoplamiento Molecular , Mariposas Nocturnas , Zea mays , Animales , Quitinasas/química , Quitinasas/genética , Quitinasas/metabolismo , Mariposas Nocturnas/enzimología , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/genética , Quitina/química , Quitina/metabolismo , Insecticidas/química , Insecticidas/farmacología , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química , Proteínas de Insectos/antagonistas & inhibidores , Zea mays/química , Zea mays/parasitología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Diseño de Fármacos , Control de Insectos , Larva/crecimiento & desarrollo , Larva/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an in vitro model to investigate the potential immune evasion strategies employed by SADS-CoV against the IFN-λ response. Our results showed that SADS-CoV infection suppressed the production of IFN-λ1 induced by poly(I:C). Through screening SADS-CoV-encoded proteins, nsp1, nsp5, nsp10, nsp12, nsp16, E, S1, and S2 were identified as antagonists of IFN-λ1 production. Specifically, SADS-CoV nsp1 impeded the activation of the IFN-λ1 promoter mediated by MAVS, TBK1, IKKε, and IRF1. Both SADS-CoV and nsp1 obstructed poly(I:C)-induced nuclear translocation of IRF1. Moreover, SADS-CoV nsp1 degraded IRF1 via the ubiquitin-mediated proteasome pathway without interacting with it. Overall, our study provides the first evidence that SADS-CoV inhibits the type III IFN response, shedding light on the molecular mechanisms employed by SADS-CoV to evade the host immune response.
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Alphacoronavirus , Infecciones por Coronavirus , Enfermedades de los Porcinos , Animales , Porcinos , Complejo de la Endopetidasa Proteasomal , Interferón lambda , Alphacoronavirus/fisiología , Ubiquitinas , Infecciones por Coronavirus/veterinariaRESUMEN
Background: In the post-American College of Surgeons Oncology Group Z0011 trial era, clinicians are attempting to preoperatively evaluate axillary lymph node (ALN) status using ultrasound. However, the value of preoperative ultrasound examination remains uncertain. The study aimed to investigate the ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS), in combination with molecular biomarkers, to predict the risk of ALN metastasis (ALNM) in clinical T1-T2 breast cancer. Methods: A retrospective case-control analysis was conducted on 168 patients with clinical T1-T2 breast cancer at Peking University First Hospital between January 2013 and August 2021. Preoperative ABVS and HHUS examinations were performed. According to the pathology results of the ALN, patients were divided into metastatic and nonmetastatic groups. Logistic regression analyses were used to analyze the ultrasonic characteristics of ABVS and HHUS on clinical T1-T2 breast cancer, and molecular biomarkers were incorporated to predict the risk of ALNM. Results: Of the 168 patients, 88 (52.4%) had ipsilateral ALNM while 80 (47.6%) had no ipsilateral ALNM. The univariate analysis showed that shorter tumor-skin distance (P=0.011), the Adler blood flow grade of II-III (P=0.014), and larger tumor size on ABVS (P<0.001) were associated with ALNM. The multivariate logistic analysis showed that these three risk factors, including the tumor-skin distance [odds ratio (OR) =0.279; P=0.024], the Adler blood flow grade (OR =2.164; P=0.046), and the tumor size on ABVS (OR =1.033; P=0.002), were independent predictive parameters. Conclusions: The tumor-skin distance, tumor size on ABVS, and Adler blood flow grade have diagnostic value for ALNM in clinical T1-T2 breast cancer.
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The surface modification technique is applied in microfluidic devices to modify wettability and achieve different flow velocities. Currently available methods for poly(dimethylsiloxane) (PDMS) surfaces may reliably induce wettability changes, but only one area can be altered at a time. This work introduces the controlled gradient oxygen plasma modification (CGPM) technique, which layers several resin masks with varying porosities on top of the PDMS surface. Selective wettability of the PDMS surface can be achieved by varying the oxygen plasma density above the modified material's surface by manipulation of the porosity value. Through the implementation of the COMSOL plasma module, the impact of the mask's porosity, through-hole size, distribution, and distance from the PDMS surface on wettability was studied. The suggested CGPM approach was characterized by contact angle measurements. During the 25-second CGPM procedure, the PDMS surface's contact angle continually changed from 8.77° to 76.98°. An integrated microfluidic device was created and manufactured to identify D-dimers to illustrate this method. In comparison with standard oxygen plasma treatment, the D-dimer assay was finished in 10 minutes and had a dynamic range of 1-1000 ng mL-1, with a peak fluorescence signal augmentation of 78.3% and an average fluorescence intensity enhancement of 31.1%.
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Curcumin is a chemical with various pharmacological activities used for cancer treatment. It inhibits hepatocellular carcinoma (HCC) by inducing apoptosis. Here, the mechanism underlying the effect of curcumin on the apoptosis of HCC cells was studied. Cell counting kit-8 and plate cloning assays were used to assess the proliferation of HCC cells, and acridine orange/ethidium bromide and Annexin V/PI staining were used to analyze their apoptosis. HCC xenograft tumor models were established to validate anti-cancer effects of curcumin. Expression levels of XRCC4 protein in tumor tissues were assessed by immunohistochemistry. Correlation between XRCC4 expression and the prognosis of patients with HCC was analyzed by integrating publicly available gene expression data. Curcumin inhibited HCC cells proliferation in a dose-dependent manner. Compared with the control group, curcumin significantly promoted the apoptosis of HCC cells in vitro and in vivo. Immunohistochemical analysis revealed that curcumin downregulated XRCC4 expression levels in HCC tissues. Prognosis of HCC patients with high XRCC4 expression was poorer than that of patients with low XRCC4 expression. Therefore, curcumin exerts anti-cancer effects by inhibiting cell proliferation and promoting cell apoptosis in HCC. This may be due to curcumin interference in the repair process of the nonhomologous DNA terminal link of HCC cells by downregulating XRCC4 expression.
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Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Curcumina/farmacología , Curcumina/uso terapéutico , Línea Celular Tumoral , Apoptosis , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
Hydrophilicity is a requisite attribute for the 2D cell culture substrate's surface, facilitating cell adhesion and spreading. Conventional poly(dimethylsiloxane) (PDMS) microfluidic chips necessitate protein coatings to enhance hydrophilicity; however, this approach is afflicted by issues of transient efficacy, interference with cell analysis, and high costs. This paper presents a protein-free microfluidic chip, termed a "microfluidic Petri dish-chip (MPD-chip)", integrating PDMS as the cover and a tissue culture-treated (TC-treated) Petri dish as the substrate. Microstructures are hot-embossed onto the Petri dish substrate using a silicon mold. This meticulous replication process serves to establish stable flow field dynamics within the chip. A simplified method for irreversible bonding, utilizing plasma activation and silylation, is proposed for affixing the PDMS cover onto the microstructured Petri dish substrate. The prepared composite chip exhibits remarkable tightness, boasting a notable bond strength of 2825 kPa. Furthermore, the composite microfluidic chip demonstrates the capability to withstand flow velocities of at least 200 µL/min, effectively meeting the required injection standards for both cell suspension and culture medium. SH-SY5Y and HeLa cells are cultured dynamically in the MPD-chip and control groups. Outcomes encompassing normalized cell density, cell adhesion area, and cell viability metrics unequivocally highlight the superiority of the MPD-chip in facilitating long-term two-dimensional (2D) cell cultures.
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Técnicas Analíticas Microfluídicas , Neuroblastoma , Humanos , Microfluídica , Técnicas Analíticas Microfluídicas/métodos , Células HeLa , Técnicas de Cultivo de Célula/métodos , ProteínasRESUMEN
Activating transcription factor 4 (ATF4) is a fundamental basic region/leucine zipper transcription factor, responds to various stress signals, and plays crucial roles in normal metabolic and stress response processes. Although its functions in human health and disease are not completely understood, compelling evidence underscores ATF4 is indispensable for multiple stages and lineages of erythroid development, including the regulation of fetal liver hematopoietic stem cells, induction of terminal erythroid differentiation, and maintenance of erythroid homeostasis. [Formula: see text]-Thalassemia is a blood disorder arising from mutations in the [Formula: see text]-globin gene. Reactivating the expression of the [Formula: see text]-globin gene in adult patients has emerged as a promising therapeutic strategy for ameliorating clinical symptoms associated with [Formula: see text]-thalassemia. Recent research has suggested that ATF4 contributes to decreased fetal hemoglobin (HbF) level through its binding to potent negative regulators of HbF, such as BCL11A and MYB. Notably, evidence also suggests a contrasting outcome where increased ATF4 protein levels are associated with enhanced HbF at the transcriptional level. Consequently, the identification of mechanisms that modulate ATF4-mediated [Formula: see text]-globin transcription and its effects on erythroid development may unveil novel targets for [Formula: see text]-thalassemia treatment.
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Caged plant growth regulators (caged PGRs) that release bioactive molecules under irradiation are critical in enhancing the efficacy and mitigating the negative environmental effects of PGRs. The synthetically derived plant growth inhibitor exo-16,17-dihydro-gibberellin A5-13-acetate (DHGA5) regulates the development and stress resilience of plants. We report here the conception of novel caged DHGA5 derivatives wherein the photoremovable protecting groups (PRPGs) serve not only to enable light-controlled release but also to protect the carboxyl group during chemical synthesis. Three o-nitrobenzyl-based caged DHGA5 derivatives with different substituents on the nitrobenzyl moiety were obtained and evaluated for their properties in vitro and in vivo. The photolysis half-life values of caged DHGA5 derivatives 7a, 7b, and 7c under a UV lamp were 15.6 h, 1.2 h, and 28.2 h, respectively. Experiments in vivo showed that 0.2 mM of the caged compounds significantly inhibited the growth of the model plant Arabidopsis thaliana and important crop rice in a precise photoactivated form.
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Arabidopsis , Reguladores del Crecimiento de las Plantas , Reguladores del Crecimiento de las Plantas/farmacología , Giberelinas , Acetatos , FotólisisRESUMEN
A precursor film is a unique microfluidic entity that arises at the liquid/solid interface. The formation mechanism of this entity in high-temperature systems is yet to be explained, mainly due to the limitations posed by the increased reaction at the solid/liquid interface. In this study, we investigate the formation process of the precursor film in high-temperature molten metal systems (Ag/Ni, Au/Ni, and Cu/Ni) using molecular dynamics simulations. The alloying energies for different alloying pairs were determined to extract the excess energy, which was found to be distributed from the interface to the upper liquid. The pattern of this energy distribution determines the shape of the near-surface liquid, including the precursor film. This relationship is further reflected by the structural disjoining pressure, which is the excess pressure exerted by the ordered microstructures within the wedge-shaped area of the droplet. Strong nonlinearity has been found in the structural disjoining pressure of Ag/Ni and Au/Ni systems, which is considered to be the main reason for the formation of the precursor film. The fluctuation of the dissolution rate is also reflected in the disjoining pressure, and the inhibition of dissolution on the precursor film formation is phenomenally clarified.
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Objective. Three-dimensional micro-nano electrodes (MNEs) with the vertical nanopillar array distributed on the surface play an increasingly important role in neural science research. The geometric parameters of the nanopillar array and the cell adhesion state on the nanopillar array are the factors that may affect the MNE recording. However, the quantified relationship between these parameters and the signal-to-noise ratio (SNR) is still unclear. This paper establishes a cell-MNE interface SNR model and obtains the mathematical relationship between the above parameters and SNR.Approach. The equivalent electrical circuit and numerical simulation are used to study the sensing performance of the cell-electrode interface. The adhesion state of cells on MNE is quantified as engulfment percentage, and an equivalent cleft width is proposed to describe the signal loss caused by clefts between the cell membrane and the electrode surface.Main results. Whether the planar substrate is insulated or not, the SNR of MNE is greater than planar microelectrode only when the engulfment percentage is greater than a certain value. Under the premise of maximum engulfment percentage, the spacing and height of nanopillars should be minimized, and the radius of the nanopillar should be maximized for better signal quality.Significance. The model can clarify the mechanism of improving SNR by nanopillar arrays and provides the theoretical basis for the design of such nanopillar neural electrodes.
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Relación Señal-Ruido , Microelectrodos , Membrana Celular , Simulación por Computador , Diseño de EquipoRESUMEN
The antitumor mechanism of curcumin is unclear, especially in hepatocellular carcinoma (HCC) cells. To clarify the mechanism of action of curcumin in the effective treatment of HCC, the targets of curcumin were screened and validated. Candidate genes of curcumin for HCC were screened using the traditional Chinese medicine systems pharmacology (TCMSP) database and validated using The Cancer Genome Atlas (TCGA) database. The correlation of mRNA expression levels between key candidate genes was identified in the TCGA liver hepatocellular carcinoma (LIHC) dataset. The effects on prognosis were analyzed to identify the target gene of curcumin, which inhibits HCC cell proliferation. Based on the subcutaneous xenograft model of human HCC in nude mice, the expression levels of target proteins were observed using immunohistochemistry. The analysis results of the present study identified the target genes of curcumin, which were obtained by screening the TCSMP database. The protein tyrosine phosphatase non-receptor type 1 (PTPN1) was obtained from TCGA database analysis of the targeted genes. The expression levels of PTPN1 and its homologous sequence genes in TCGA LIHC project was analyzed to identify the potential target gene of curcumin, for use in HCC treatment. Next, xenograft experiments were performed to investigate the therapeutic effects of curcumin in an animal model. Curcumin was demonstrated to inhibit the growth of HCC xenograft tumors in mice. Immunohistochemistry results demonstrated that the protein expression levels of PTPN1 and PTPN11 in the curcumin group were significantly lower compared with those in the control group. In conclusion, these results demonstrated that curcumin inhibits the proliferation of HCC cells by inhibiting the expression of PTPN1 and PTPN11.