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We present a 4×4 real-valued channel equalizer with embedded phase estimator, designed for carrier phase and frequency offset estimation and compensation in coherent optical communications with in-phase/quadrature (IQ) impairments. These impairments include IQ timing skew, gain imbalance, and quadrature phase errors at the transmitter side. To achieve adaptive control of the equalizer's filter coefficients, we employ the decision-directed least mean square (DD-LMS) algorithm. This algorithm minimizes the error between the filter outputs and the desired signals in a symbol-by-symbol manner, resulting in faster channel coefficients adaptation speed. Simulation results for a 60 GBaud polarization-multiplexing 16 quadrature amplitude modulation (PM-16QAM) signal demonstrate that our proposed equalizer outperforms a 2×2 cascaded multi modulus algorithm-based (CMMA-based) equalizer, a 2×2 complex-valued method based on the DD-LMS algorithm, and the 4×4 real-valued equalizer without embedded frequency offset estimation (FOE), when the transmitter IQ impairments exist. Experimental validation is also conducted for the 60 GBaud PM-16QAM and 45 GBaud PM-64QAM signals. Similar to the simulation results, our experiments show that the proposed 4×4 real-valued equalizer with embedded FOE can achieve effective SNR penalties of less than 0.41 dB at 7 ps skew, 1.33 dB at 3.5 dB gain imbalance, and 1.64 dB at the bias voltage shift of 0.5 V for the 60 GBaud PM-16QAM signal. Finally, our experimental results confirm the effectiveness of our proposed method in carrier phase estimation as well as the frequency offset compensation, when compared with 4×4 real-valued equalizer without embedded FOE.
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Integrating optoelectronic devices with various functions into a monolithic chip is a popular research frontier. The top-down integration scheme on silicon-based III-nitride wafers has unique advantages. A monolithic III-nitride on-chip system with lighting source, electrical absorption modulator, waveguide and photodetector with the same structure were designed and fabricated to discover the asymmetry of photon emission and absorption in quantum well diode. The characteristics of the chip were characterized in detail and three different spectral redshifts were observed in the experiment. Results revealed that the asymmetric absorption causes spectral redshift in a quantum well diode, and self-absorption is a fundamental and universal phenomenon in quantum wells. This work provides an important reference for future III-nitride optoelectronic integration.
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In this paper, a new method for rotational angle and speed measurements is proposed by integrating a GaN optoelectronic chip with a stepped disc. The optoelectronic chip that integrates a light-emitting diode (LED) and a photodiode (PD) is fabricated by wafer-level microfabrication. The disc is designed with a spiral staircase shape, and has increasing thickness distribution along the circumferential direction. The sensing mechanism is that the optoelectronic chip measures angle-dependent intensity change of the light reflected off the stepped disc. Through a series of performance tests, the chip is highly sensitive to a continuous rotation from 0 ∘ to 360 ∘, and produces photocurrent to indicate the rotational angle and speed. A rotational speed up to 5000 rpm is measured with a relative error less than 1.27%. The developed sensing architecture provides an alternative solution for constructing a low-cost, miniaturized, and high-efficiency rotational angle and speed sensing system.
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A large-sized multiple quantum well (MQW) light-emitting diode (LED) integrated with a thermopile for on-chip temperature and power monitoring is presented in this study. Seven thermopile structures, fully compatible with the fabrication of LEDs, are strategically placed at different locations on the LED to monitor its temperature during the operation. Additionally, the thermopile allows for monitoring the power of the LED, as there exists an approximate linear relationship between the light output power and temperature. Compared to traditional methods of measuring LED temperature, the thermopile offers several advantages, including no moving parts, long lifetime, no maintenance, high reliability, and direct conversion without intermediate processes. The results demonstrate that the integration of the thermopiles onto the LED provides superior temperature and power monitoring capabilities. Furthermore, this integrated solution has the potential to enable real-time management and control of LED temperature.
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The gallium nitride (GaN) integrated optical transceiver chip based on multiple quantum wells (MQW) structure exhibits great promise in the fields of communication and sensing. In this Letter, the effect of ambient temperature on the performance of GaN-integrated optical transceiver chips including a blue MQW light-emitting diode (LED) and a MQW photodiode (PD) is comprehensively studied. Temperature-dependent light-emitting and current-voltage characteristics of the blue MQW LEDs are measured with the ambient temperature ranging from -70°C to 120°C. The experimental results reveal a decline in the electroluminescent (EL) intensity and an obvious redshift in the emission peak wavelength of the LED with increasing ambient temperature. The light detection performance of MQW PD under different temperatures is also measured with the illumination of an external blue MQW LED, indicating an enhancement in the PD sensitivity as the temperature rises. Finally, the temperature effect on the MQW PD under the illumination of the MQW LED on the GaN-integrated optical transceiver chip is characterized, and the PD photocurrent increases with higher ambient temperature. Furthermore, the measured temperature characteristics indicate that the GaN-integrated optical transceiver chip offers a promising application potential for optoelectronic temperature sensor.
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This Letter reports a collinear optical interconnect architecture for acoustic sensing via a monolithic integrated GaN optoelectronic chip. The chip is designed with a ring-shaped photodiode (PD) surrounding a light-emitting diode (LED) of a spectral range from 420-530 nm. The axisymmetric structure helps the coaxial propagation of light transmission and reception. By placing this multiple-quantum wells (MQW)-based device and a piece of aluminum-coated polyethylene terephthalate (Al/PET) film on fiber ends, an ultra-compact acoustic sensing system is built. The sound vibrations can be simply detected by direct measurement of the diaphragm deformation-induced power change. An average signal noise ratio (SNR) of 40 dB and a maximum sensitivity of 82 mV/Pa are obtained when the acoustic vibration frequency changes from 400 Hz to 3.2 kHz. This work provides a feasible solution to miniaturize the sensing system footprint and reduce the cost.
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BACKGROUND: PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types. METHODS: The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures. RESULTS: In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown. CONCLUSIONS: Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Técnicas de Silenciamiento del Gen , Neoplasias Pulmonares , Neovascularización Patológica , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Humanos , Transición Epitelial-Mesenquimal/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Línea Celular Tumoral , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , Células A549 , Persona de Mediana EdadRESUMEN
Immunoglobulin G (IgG) autoantibodies can lead to the formation of autoimmune diseases through Fab and/or Fc-mediated interactions with host molecules as well as activated T cells. The neonatal Fc receptor (FcRn) binds at acidic pH IgG and albumin, and the mechanism for prolonging serum IgG half-life is making IgG re-entry into circulation by prompting it not to be degraded by lysosomes and back to the cell surface. Given the FcRn receptor's essential role in IgG homeostasis, one of the strategies to promote the quick degradation of endogenous IgG is to suppress the function of FcRn, which is beneficial to the treatment of IgG-driven autoimmune disorders like myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), stiff person syndrome, and immune thrombocytopenia (ITP). We elaborately read the literature about efgartigimod and systematically reviewed the research progress and clinical application of this novel FcRn inhibitor in autoimmune diseases. Efgartigimod is the firstly FcRn antagonist developed and was approved on 17 December 2021 by the United States for the therapy of acetylcholine receptor-positive MG. In January 2022, efgartigimod received its second regulatory approval in Japan. In addition, the market authorization application in Europe was submitted and validated in August 2021. China's National Medical Products Administration officially accepted the marketing application of efgartigimod on July 13, 2022. To suppress the function of FcRn, which is beneficial to the treatment of IgG-driven autoimmune disorders like MG, CIDP, ITP, and stiff person syndrome. We review the rationale, clinical evidence, and future perspectives of efgartigimod for the treatment of autoimmune disease.
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Enfermedades Autoinmunes , Antígenos de Histocompatibilidad Clase I , Receptores Fc , Humanos , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Animales , Inmunoglobulina GRESUMEN
Alzheimer's disease (AD) lacks effective clinical treatments. As the disease progresses, the cerebral glucose hypometabolism that appears in the preclinical phase of AD gradually worsens, leading to increasingly severe brain energy disorders. This review analyzes the brain energy deficit in AD and its etiology, brain energy rescue strategies based on ketone intervention, the effects and mechanisms of IF, the differences in efficacy between IF and ketogenic diet and the duality of IF. The evidence suggests that brain energy deficits lead to the development and progression of AD pathology. IF, which improves brain energy impairments by promoting ketone metabolism, thus has good therapeutic potential for AD.
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Enfermedad de Alzheimer , Dieta Cetogénica , Humanos , Enfermedad de Alzheimer/metabolismo , Cuerpos Cetónicos/metabolismo , Ayuno Intermitente , Encéfalo/metabolismo , Cetonas/metabolismoRESUMEN
H1.4 is one of the 11 variants of linker histone H1, and is associated with tumorigenesis and development of various cancers. However, it is unclear for the role of histone H1.4 in non-small cell lung cancer (NSCLC). In this study, we found that overexpression of H1.4 significantly inhibited the cell viability, migration, invasion and epithelial-mesenchymal transition (EMT) processes, whereas silencing H1.4 by shRNA knockdown promoted these processes in NSCLC cell lines A549 and H1299. We further showed that H1.4 overexpression reduced ERK1/2 expression or its phosphorylation levels, while H1.4 knockdown increased ERK1/2 expression or phosphorylation levels in NSCLC. Furthermore, we demonstrated that H1.4 bound to the promoter of ERK1/2, and acted as a transcriptional suppressor to inhibit ERK1/2 expression in A549 or H1299 cells. Importantly, we found that ERK ecto-expression can largely recovered the inhibitory effects of H1.4 on cell viability, migration, invasion and EMT processes. In summary, our study reveals that the H1.4-ERK pathway is crucial for cell viability, migration, invasion and EMT of NSCLC and could be a therapeutic target for NSCLC.
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A core-shell ZIF-67@ZIF-8-derived Co nanoparticles embedded in N-doped carbon nanotube polyhedra (Co/C-NCNP) hybrid nanostructure was prepared by a pyrolysis method. The synthesized Co/C-NCNP was modified on the screen-printed carbon electrode and used for the portable wireless sensitive determination of breviscapine (BVC) by differential pulse voltammetry. The Co/C-NCNP had a large surface area and excellent catalytic activity with increasing Co sites to combine with BVC for selective determination, which led to the improvement of the sensitivity of the electrochemical sensor. Under optimized conditions, the constructed sensor had linear ranges from 0.15 to 20.0 µmol/L and 20.0 to 100.0 µmol/L with the limit of detection of 0.014 µmol/L (3S0/S). The sensor was successfully applied to BVC tablet sample analysis with satisfactory results. This work provided the potential applications of zeolitic imidazolate framework-derived nanomaterials in the fabrication of electrochemical sensors for the sensitive detection of drug samples.
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Glucagon receptor (GCGR) is a class B1 G-protein-coupled receptor that plays a crucial role in maintaining human blood glucose homeostasis and is a significant target for the treatment of type 2 diabetes mellitus (T2DM). Currently, six small molecules (Bay 27-9955, MK-0893, MK-3577, LY2409021, PF-06291874, and LGD-6972) have been tested or are undergoing clinical trials, but only the binding site of MK-0893 has been resolved. To predict binding sites for other small molecules, we utilized both the crystal structure of the GCGR and MK-0893 complex and dynamic conformations. We docked five small molecules and selected the best conformation based on binding mode, docking score, and binding free energy. We performed MD simulations to verify the binding mode of the selected small molecules. Moreover, when selecting conformations, results of competitive binding were referred to. MD simulation indicated that Bay 27-9955 exhibits moderate binding stability in Pocket 3. MK-3577, LY2409021, and PF-06291874 exhibited highly stable binding to Pocket 2, consistent with experimental results. However, LY2409021 may also bind to Pocket 5. Additionally, LGD-6972 exhibited relatively stable binding in Pocket 5. We also conducted structural modifications of LGD-6972 based on the results of MD simulations and predicted its analogues' bioavailability, providing a reference for the study of GCGR small molecules.
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Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Conformación Proteica , Receptores de Glucagón , Sitios de Unión , Humanos , Cristalografía por Rayos X , Receptores de Glucagón/química , Receptores de Glucagón/metabolismo , Unión Proteica , Bibliotecas de Moléculas Pequeñas/química , Ligandos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismoRESUMEN
Metallic catalyst modification by organic ligands is an emerging catalyst design in enhancing the activity and selectivity of electrocatalytic carbon dioxide (CO2) reactive capture and reduction to value-added fuels. However, a lack of fundamental science on how these ligand-metal interfaces interact with CO2 and key intermediates under working conditions has resulted in a trial-and-error approach for experimental designs. With the aid of density functional theory calculations, we provided a comprehensive mechanism study of CO2 reduction to multicarbon products over aminothiolate-coated copper (Cu) catalysts. Our results indicate that the CO2 reduction performance was closely related to the alkyl chain length, ligand coverage, ligand configuration, and Cu facet. The aminothiolate ligand-Cu interface significantly promoted initial CO2 activation and lowered the activation barrier of carbon-carbon coupling through the organic (nitrogen (N)) and inorganic (Cu) interfacial active sites. Experimentally, the selectivity and partial current density of the multicarbon products over aminothiolate-coated Cu increased by 1.5-fold and 2-fold, respectively, as compared to the pristine Cu at -1.16 VRHE, consistent with our theoretical findings. This work highlights the promising strategy of designing the ligand-metal interface for CO2 reactive capture and conversion to multicarbon products.
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MOTIVATION: The presence of tumor cell clusters in pleural effusion may be a signal of cancer metastasis. The instance segmentation of single cell from cell clusters plays a pivotal role in cluster cell analysis. However, current cell segmentation methods perform poorly for cluster cells due to the overlapping/touching characters of clusters, multiple instance properties of cells, and the poor generalization ability of the models. RESULTS: In this article, we propose a contour constraint instance segmentation framework (CC framework) for cluster cells based on a cluster cell combination enhancement module. The framework can accurately locate each instance from cluster cells and realize high-precision contour segmentation under a few samples. Specifically, we propose the contour attention constraint module to alleviate over- and under-segmentation among individual cell-instance boundaries. In addition, to evaluate the framework, we construct a pleural effusion cluster cell dataset including 197 high-quality samples. The quantitative results show that the numeric result of APmask is > 90%, a more than 10% increase compared with state-of-the-art semantic segmentation algorithms. From the qualitative results, we can observe that our method rarely has segmentation errors.
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Algoritmos , Derrame Pleural , Análisis por Conglomerados , HumanosRESUMEN
Lightweight, low-cost, and simple systems for magnetic field sensing are in high demand. Here, we demonstrate such a magnetic field sensing system by integrating a light source, detector, magnetic fluid (MF), and plastic optical fiber (POF). Two bifunctional AlGaInP diodes with identical multiple-quantum well structures separately function as the light source and the detector of the sensing system due to the partial overlap between the electroluminescence and responsivity spectra. Magnetic field sensing is realized by changing the amount of reflected light due to the change in reflection coefficient of the POF/MF interface caused by the ambient magnetic field. The chip-integrated POF magnetic field sensor exhibits a reliable operation with a detection range from 10 Gs to 400 Gs. The results indicate that the chip-integrated POF sensor is promising for magnetic field sensing.
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III-nitride optoelectronic chips have tremendous potential for developing integrated computing and communication systems with low power consumption. The monolithic, top-down approaches are advantageous for simplifying the fabrication process and reducing the corresponding manufacturing cost. Herein, an ultraviolet optical interconnection system is investigated to discover the way of multiplexing between emission and absorption modulations on a monolithic optoelectronic chip. All on-chip components, the transmitter, monitor, waveguide, modulator, and receiver, share the same quantum well structure. As an example, two bias-controlled modulation modes are used to modulate video and audio signals in the experiment presented in this Letter. The results show that our on-chip optoelectronic system works efficiently in the near ultraviolet band, revealing the potential breadth of GaN optoelectronic integration.
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The combination of plastic optical fiber (POF) with monolithically integrated transmitter and receiver is becoming increasingly attractive for the development of miniature optoelectronic sensing systems. Here, we propose a temperature sensing system by integrating a GaN optoelectronic chip with a POF and aluminum (Al) reflector. Owing to the overlap between electroluminescence and responsivity spectra of multiple quantum well (MQW) diodes, both the transmitter and the receiver having identical MQW structures are monolithically integrated on a tiny GaN chip by using the same fabrication process flow. Environmental temperature change leads to thermal deformation in the Al reflector, which reflects the transmitted light back with a light pulse. The reflected light is coupled into the guided POF again and sensed by the on-chip receiver. Finally, the temperature information is read out as electrical signals. When the ambient temperature changes from 20.1°C to 100°C, the optically induced electrical signal decreases from -3.04 µA to -3.13 µA. The results suggest that the monolithically integrated GaN device offers a promising option for optoelectronic temperature sensing systems.
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BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects. OBJECTIVE: To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms. METHODS: We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis. RESULTS: The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P = .004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P = .118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols. LIMITATIONS: The cohort size is relatively small. Both cohorts had low overall SCORTEN scores. CONCLUSION: Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN.
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Síndrome de Stevens-Johnson , Humanos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/complicaciones , Estudios Prospectivos , Adalimumab/efectos adversos , Proteómica , Pronóstico , Corticoesteroides/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) are critical regulators in the initiation and progression of breast cancer. Our study aims to characterize the functions of LINC02086 which few published in breast cancer and decipher the downstream molecular mechanisms. METHODS: LINC02086 expression is tested in RNA-seq data from GEPIA database, tumor tissue samples from hospital patients and breast cancer cell lines. LINC02086 was silenced or overexpressed by lenti-virus-mediated shRNAs, or pLVX-Puro plasmids. Luciferase reporter assay and RNA pull-down assay were applied to study interactions between LINC02086, miR-6757-5p and ephrin type-A receptor 2 (EPHA2). LINC02086-silencing MCF-7 cells were injected into mice to establish xenograft animal models. RESULTS: Using RNA-seq data, tumor tissue samples and breast cancer cells, LINC02086 was consistently found to be up-regulated in breast cancer, and correlated with poorer prognosis. LINC02086 knockdown decreased cell viability, promoted cell apoptosis and suppressed tumor growth. LINC02086 interacted with miR-6757-5p that interacted with EPHA2.LINC02086 expression was negatively correlated with miR-6757-5p expression (r = -0.5698, P < 0.001) but was positively correlated with EPHA2 expression (r = 0.5061, P < 0.001). miR-6757-5p expression was negatively correlated with EPHA2 expression (r = -0.5919, P < 0.001). LINC02086 regulated EPHA2 via miR-6757-5p. miR-6757-5p/EPHA2 axis was a mediator of the effect of LINC02086 on cell viability and apoptosis. CONCLUSION: LINC02086 increases cell viability and decreases apoptotic cells in breast cancer by sponging miR-6757-5p to upregulate EPHA2. This study presents LINC02086/miR-6757-5p/EPHA2 axis as promising therapeutic targets for breast cancer intervention.
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Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Animales , Femenino , Humanos , Ratones , Apoptosis/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Black phosphorene quantum dots (BPQDs) were prepared by ultrasonic-assisted liquid-phase exfoliation and centrifugation with morphologies proved by TEM results. Furthermore, an electrochemical enzyme sensor was prepared by co-modification of BPQDs with horseradish peroxidase (HRP) on the surface of a carbon ionic liquid electrode (CILE) for the first time. The direct electrochemical behavior of HRP was studied with a pair of well-shaped voltammetric peaks that appeared, indicating that the existence of BPQDs was beneficial to accelerate the electron transfer rate between HRP and the electrode surface. This was due to the excellent properties of BPQDs, such as small particle size, high interfacial reaction activity, fast conductivity, and good biocompatibility. The presence of BPQDs on the electrode surface provided a fast channel for direct electron transfer of HRP. Therefore, the constructed electrochemical HRP biosensor was firstly used to investigate the electrocatalytic behavior of trichloroacetic acid (TCA) and potassium bromate (KBrO3), and the wide linear detection ranges of TCA and KBrO3 were 4.0-600.0 mmol/L and 2.0-57.0 mmol/L, respectively. The modified electrode was applied to the actual samples detection with satisfactory results.