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Dopamine (DA), ascorbic acid (AA), and uric acid (UA) are crucial neurochemicals, and their abnormal levels are involved in various neurological disorders. While electrodes for their detection have been developed, achieving the sensitivity required for in vivo applications remains a challenge. In this study, we proposed a synthetic Au24Cd nanoenzyme (ACNE) that significantly enhanced the electrochemical performance of metal electrodes. ACNE-modified electrodes demonstrated a remarkable 10-fold reduction in impedance compared to silver microelectrodes. Furthermore, we validated their excellent electrocatalytic activity and sensitivity using five electrochemical detection methods, including cyclic voltammetry, differential pulse voltammetry, square-wave pulse voltammetry, normal pulse voltammetry, and linear scanning voltammetry. Importantly, the stability of gold microelectrodes (Au MEs) modified with ACNEs was significantly improved, exhibiting a 30-fold enhancement compared to Au MEs. This improved performance suggests that ACNE functionalization holds great promise for developing micro-biosensors with enhanced sensitivity and stability for detecting small molecules.
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Ácido Ascórbico , Técnicas Biossensoriais , Dopamina , Técnicas Eletroquímicas , Ouro , Microeletrodos , Ácido Úrico , Dopamina/análise , Ouro/química , Ácido Ascórbico/análise , Ácido Úrico/análise , Prata/química , Cádmio/análiseRESUMO
Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.
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Febre , Transplante de Células-Tronco Hematopoéticas , Aprendizado de Máquina , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Febre/etiologia , Febre/diagnóstico , Febre/sangue , Algoritmos , MicroRNAs/sangue , Biomarcadores/sangue , Adolescente , Adulto JovemRESUMO
Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.
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BACKGROUND: Hexokinase I (HK1) is highly expressed in a variety of malignancies, regulates glycolytic pathway in cancer cells, and thus considered to be one of the promising molecular targets for cancer therapy. Nonetheless, the development of a specific inhibitor against HK1 remains elusive. PURPOSE: This study aims to elucidate the mechanism by which oridonin inhibits the proliferation and immune evasion of bladder cancer cells, specifically through the suppression of HK1. METHODS: To examine the mechanisms by which oridonin directly binds to cysteines of HK1 and inhibits bladder cancer growth, this study utilized a variety of methods. These included the Human Proteome Microarray, Streptavidin-agarose affinity assay, Biolayer Interferometry (BLI) ainding analysis, Mass Spectrometry, Cellular Thermal Shift Assay, Extracellular Acidification Rate measurement, and Xenotransplant mouse models. RESULTS: As indicated by our current findings, oridonin forms a covalent bond with Cys-813, located adjacently to glucose-binding domain of HK1. This suppresses the enzymatic activity of HK1, leading to an effective reduction of glycolysis, which triggers cell death via apoptosis in cells derived from human bladder cancer. Significantly, oridonin also inhibits lactate-induced PD-L1 expression in bladder cancer. Furthermore, pairing oridonin with a PD-L1 inhibitor amplifies the cytotoxicity of CD8+ T cells against bladder cancer. CONCLUSION: This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.
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Antineoplásicos , Diterpenos do Tipo Caurano , Neoplasias da Bexiga Urinária , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/química , Antineoplásicos/farmacologia , Proliferação de Células , ApoptoseRESUMO
Implanted neural electrodes have been widely used to treat brain diseases that require high sensitivity and biocompatibility at the tissue-electrode interface. However, currently used clinical electrodes cannot meet both these requirements simultaneously, which hinders the effective recording of electronic signals. Herein, nanozyme-based neural electrodes incorporating bioinspired atomically precise clusters are developed as a general strategy with a heterogeneous design for multiscale and ultrasensitive neural recording via quantum transport and biocatalytic processes. Owing to the dual high-speed electronic and ionic currents at the electrode-tissue interface, the impedance of nanozyme electrodes is 26 times lower than that of state-of-the-art metal electrodes, and the acquisition sensitivity for the local field potential is ≈10 times higher than that of clinical PtIr electrodes, enabling a signal-to-noise ratio (SNR) of up to 14.7 dB for single-neuron recordings in rats. The electrodes provide more than 100-fold higher antioxidant and multi-enzyme-like activities, which effectively decrease 67% of the neuronal injury area by inhibiting glial proliferation and allowing sensitive and stable neural recording. Moreover, nanozyme electrodes can considerably improve the SNR of seizures in acute epileptic rats and are expected to achieve precise localization of seizure foci in clinical settings.
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Neurônios , Ratos , Animais , Eletrodos , Eletrodos Implantados , Razão Sinal-Ruído , Neurônios/fisiologia , Impedância Elétrica , MicroeletrodosRESUMO
Effective depolymerization of lignin is the most important step for its comprehensive utilization. So far, most of the studies on depolymerization of lignin focused on batch processing, whereas only a few studies relied on the microreactor. In this study, we developed a continuous-flow microreactor for depolymerization of lignin into monomeric and oligomeric compounds. The yields of monomers and oligomers can be adjusted by varying the temperature, pressure, residence time, NaOH dosage, and solvent. Under optimized conditions, the lignin conversion rate was 77.73 wt %, and the monomer yield was 13.26 wt %, with 77.81% being phenolic compounds. In addition, comparative characterizations on the raw lignin and products demonstrated that the oil products were mainly composed of phenolic tetramers and trimers, and the effective cleavage of the ß-O-4 linkage of S-type lignin was responsible for the high yield of 2,6-dimethoxyphenol. It indicated that raw lignin could be effectively depolymerized continuously using the continuous-flow microreactor, and it will be a new strategy for comprehensive utilization of lignin to produce fine-chemical intermediates.
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Lignina , Fenóis , Lignina/química , Catálise , Polimerização , Solventes/químicaRESUMO
The performance of supercapacitors is directly influenced by the conductivity of polypyrrole, which serves as the electrode material. In order to balance considerations of cost-effectiveness and conductivity, this study employs magnetron sputtering to fabricate a copper-tin alloy layer as the conductive layer for polypyrrole. The deposition of a copper-tin alloy film through magnetron sputtering has a significant impact on the polymerization effect of pyrrole as well as being a crucial factor influencing the performance of supercapacitors. Various parameters, including working pressure, sputtering time, and sputtering power, affect the conductivity of the copper-tin alloy film. Furthermore, the degree of influence of each parameter on the conductivity of the copper-tin alloy film varies. This study utilizes an orthogonal experimental design to investigate the impact of various factors and levels on the conductivity and uniformity of a metal film. The objective is to optimize the process parameters for the creation of a copper-tin alloy film with desirable characteristics. Experimental results indicate that the working voltage, sputtering time, and sputtering power significantly influence the coefficient of variation, deposition rate, target current, and operating voltage of the film. Furthermore, FT-IR, XRD, and SEM tests are conducted on samples prepared using the identified optimal process parameters. In addition, we demonstrate various approaches to enhance the experiment's reliability. The findings indicate that the most favorable process parameters for achieving optimal results are a working pressure of 0.065 Pa, a sputtering time of 20 min, and a sputtering power of 70 W. It was observed that the sputtering time significantly influences the uniformity of the copper-tin alloy film, whereas the sputtering power has a minimal impact on its uniformity. The deposition rate is primarily influenced by the working pressure, with the greatest effect observed. Conversely, the sputtering time has the least impact on the deposition rate. Similarly, the target current is predominantly affected by the sputtering power, exhibiting the greatest influence, while the sputtering time has the least effect. Furthermore, the working voltage is most significantly influenced by the working pressure, whereas the sputtering time has the least impact on the working voltage.
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Finding cancer-driver genes has been a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth, which we named cancer-keeper genes (CKGs). Intervening CKGs may rectify aberrant cell growth, making them potential cancer therapeutic targets. We introduced control-hub genes and developed an efficient algorithm by extending network controllability theory. Control hub are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA). All genes on the cell-cycle and p53 pathways in BLCA were identified as CKGs, showing their importance in cancer. We discovered that sensitive CKGs - genes easily altered by structural perturbation - were particularly suitable therapeutic targets. Experiments on cell lines and a mouse model confirmed that six sensitive CKGs effectively suppressed cancer cell growth, demonstrating the immense therapeutic potential of CKGs.
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In this paper, a 3D printing system for a thermal battery electrode ink film is set up and investigated based on the on-demand microdroplet ejection technology. The optimal structural dimensions of the spray chamber and metal membrane of the micronozzle are determined via simulation analysis. The workflow and functional requirements of the printing system are set up. The printing system includes a pretreatment system, piezoelectric micronozzle, motion control system, piezoelectric drive system, sealing system, and liquid conveying system. Different printing parameters are compared to obtain optimized printing parameters, which can be attributed to the optimal pattern of the film. The feasibility and controllability of 3D printing methods are verified by printing tests. The size and output speed of the droplets can be controlled by adjusting the amplitude and frequency of the driving waveform acting on the piezoelectric actuator. So, the required shape and thickness of the film can be achieved. An ink film in terms of nozzle diameter = 0.6 mm, printing height = 8 mm, wiring width = 1 mm, input voltage = 3 V and square wave signal frequency = 35 Hz can be achieved. The electrochemical performance of thin-film electrodes is crucial in thermal batteries. The voltage of the thermal battery reaches its peak and tends to flatten out at around 100 s when using this printed film. The electrical performance of the thermal batteries using the printed thin films is found to be stable. This stabilized voltage makes it applicable to thermal batteries.
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BACKGROUND: Although the aberrant activation of NOTCH1 pathway causes a malignant progression of renal cell carcinoma (RCC), the precise molecular mechanisms behind the potential action of pro-oncogenic NOTCH1/HES1 axis remain elusive. Here, we examined the role of tumor suppressive miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC. METHODS: This study employed bioinformatics, xenotransplant mouse models, ChIP assay, luciferase reporter assay, functional experiments, real-time PCR and Western blot analysis to explore the mechanisms of miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC, and further explored miR-138-2-containing combination treatment strategies. RESULTS: There existed a positive correlation between down-regulation of miR-138 and the aberrant augmentation of NOTCH1/HES1 regulatory axis. Mechanistically, HES1 directly bound to miR-138-2 promoter region and thereby attenuated the transcription of miR-138-5p as well as miR-138-2-3p. Further analysis revealed that miR-138-5p as well as miR-138-2-3p synergistically impairs pro-oncogenic NOTCH1 pathway through the direct targeting of APH1A, MAML1 and NOTCH1. CONCLUSIONS: Collectively, our current study strongly suggests that miR-138-2 acts as a novel epigenetic regulator of pro-oncogenic NOTCH1 pathway, and that the potential feedback regulatory loop composed of HES1, miR-138-2 and NOTCH1 contributes to the malignant development of RCC. From the clinical point of view, this feedback regulatory loop might be a promising therapeutic target to treat the patients with RCC.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Animais , Humanos , Camundongos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismoRESUMO
Neuron interface devices can be used to explore the relationships between neuron firing and synaptic transmission, as well as to diagnose and treat neurological disorders, such as epilepsy and Alzheimer's disease. It is crucial to exploit neuron devices with high sensitivity, high biocompatibility, multifunctional integration and high-speed data processing. During the past decades, researchers have made significant progress in neural electrodes, artificial sensory neuron devices, and neuromorphic optic neuron devices. The main part of the review is divided into two sections, providing an overview of recently developed neuron interface devices for recording electrophysiological signals, as well as applications in neuromodulation, simulating the human sensory system, and achieving memory and recognition. We mainly discussed the development, characteristics, functional mechanisms, and applications of neuron devices and elucidated several key points for clinical translation. The present review highlights the advances in neuron devices on brain-computer interfaces and neuroscience research.
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BACKGROUND: Protein arginine methyltransferases (PRMTs) regulate protein biological activity by modulating arginine methylation in cancer and are increasingly recognized as potential drug targets. Inhibitors targeting PRMTs are currently in the early phases of clinical trials and more candidate drugs are needed. Flavokawain A (FKA), extracted from kava plant, has been recognized as a potential chemotherapy drug in bladder cancer (BC), but its action mechanism remains unclear. METHODS: We first determined the role of a type II PRMT, PRMT5, in BC tissue samples and performed cytological experiments. We then utilized bioinformatics tools, including computational simulation, virtual screening, molecular docking, and energy analysis, to identify the potential use of PRMT5 inhibitors for BC treatment. In vitro and in vivo co-IP and mutation assays were performed to elucidate the molecular mechanism of PRMT5 inhibitor. Pharmacology experiments like bio-layer interferometry, CETSA, and pull-down assays were further used to provide direct evidence of the complex binding process. RESULTS: Among PRMTs, PRMT5 was identified as a therapeutic target for BC. PRMT5 expression in BC was correlated with poor prognosis and manipulating its expression could affect cancer cell growth. Through screening and extensive experimental validation, we recognized that a natural product, FKA, was a small new inhibitor molecule for PRMT5. We noticed that the product could inhibit the action of BC, in vitro and in vivo, by inhibiting PRMT5. We further demonstrated that FKA blocks the symmetric arginine dimethylation of histone H2A and H4 by binding to Y304 and F580 of PRMT5. CONCLUSIONS: In summary, our research strongly suggests that PRMT5 is a potential epigenetic therapeutic target in bladder cancer, and that FKA can be used as a targeted inhibitor of PRMT5 for the treatment of bladder cancer.
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Produtos Biológicos , Neoplasias da Bexiga Urinária , Arginina , Chalcona/análogos & derivados , Inibidores Enzimáticos/farmacologia , Histonas/metabolismo , Humanos , Simulação de Acoplamento Molecular , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genéticaRESUMO
Neural electrodes have been widely used to monitor neurological disorders and have a major impact on neuroscience, whereas traditional electrodes are limited to their inherent high impedance, which makes them insensitive to weak signals during recording neural signals. Herein, we developed a neural electrode based on the graphene/Ag van der Waals heterostructure for improving the detection sensitivity and signal-to-noise ratio (SNR). The impedance of the graphene/Ag electrode is reduced to 161.4 ± 13.4 MΩ µm2, while the cathode charge-storage capacity (CSCc) reaches 24.2 ± 1.9 mC cm-2, which is 6.3 and 48.4 times higher than those of the commercial Ag electrodes, respectively. Density functional theory (DFT) results find that the Ag-graphene interface has more doped electronic states, providing faster electron transfer and enhanced interfacial transport. In vivo detection sensitivity and SNR of graphene/Ag electrodes are significantly improved. The current work provides a feasible solution for designing brain electrodes to monitor neural signals more sensitively and accurately.
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Grafite , Encéfalo , Impedância Elétrica , Eletrodos , Grafite/química , Razão Sinal-RuídoRESUMO
Near-infrared-II (NIR-II, 1000-1700 nm) fluorescence imaging is widely used for in vivo biological imaging. With the unique electronic structures and capability of band-gap engineering, two-dimensional (2D) materials can be potential candidates for NIR-II imaging. Herein, a theoretical investigation of the electronic structure and optical properties of iodine (I)-doped monolayer MoTe2 systems with different doping concentrations is carried out through simulations to explore their NIR optical properties. The results suggest that the emergence of impurity levels due to I doping effectively reduces the bandwidth of I-doped monolayer MoTe2 systems, and the bandwidth decreases with the increase in the I doping concentration. Although the I and Mo atoms possess clear covalent-bonding features according to the charge density difference, impurity levels induced by the strong hybridization between the I 5p and Mo 4d orbitals cross the Fermi level, making the doped systems exhibit metallic behavior. In addition, with the increase in the I doping concentration, the energy required for electron transition from valence bands to impurity levels gradually decreases, which can be linked to the enhancement of the optical absorption in the red-shifted NIR-II region. Meanwhile, with a higher I doping concentration, the emission spectra, which are the product of the absorption spectra and quasi-Fermi distributions for electrons and holes, can be enhanced in the NIR-II window.
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Bladder cancer is a common tumor with a high recurrence rate and high fatality rate, and its mechanism of occurrence and development remains unclear. Many proteins and metabolites reprogram at different stages of tumor development to support tumor cell growth. The moonlighting effect happens when a protein performs multiple functions simultaneously in a cell. In this study, we identified a metabolic protein, MTHFD2, which participates in the cell cycle by binding to CDK2 in bladder cancer. MTHFD2 has been shown to affect bladder cancer cell growth, which is independent of its metabolic function. We found that MTHFD2 was involved in cell cycle regulation and could encourage cell cycle progression by activating CDK2 and sequentially affecting E2F1 activation. In addition, moonlighting MTHFD2 might be regulated by the dynamics of the mitochondria. In conclusion, MTHFD2 localizes in the nucleus to perform a distinct function of catalyzing metabolic reactions. Moreover, the nuclear MTHFD2 activates CDK2 and promotes bladder cancer cell growth by modulating the cell cycle.
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Aminoidrolases/genética , Quinase 2 Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Enzimas Multifuncionais/genética , Neoplasias da Bexiga Urinária/genética , Aminoidrolases/metabolismo , Animais , Ciclo Celular/genética , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Ativação Enzimática/genética , Feminino , Células HEK293 , Humanos , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Enzimas Multifuncionais/metabolismo , Ligação Proteica , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapiaRESUMO
Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag-S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 µM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.
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Catálise , Catalase/genéticaRESUMO
As the transmembrane receptor of Netrin-1, the tumor suppressor gene Unc-5 Netrin Receptor C (UNC5C) can trigger apoptosis. Although its tumor suppressor effects have been demonstrated in solid tumors such as colon cancer, there is still a lack of systematic research on its expression regulation mechanism. To address this need, we analyzed datasets from The Cancer Genome Atlas (TCGA) database, including multi-omics data for 32 types of cancers and 10,967 cases. Analysis of these data revealed a trend of significantly decreased UNC5C expression in 16 types of solid tumors. Additionally, low UNC5C expression is related to poor prognosis of five types of tumors and restoring the expression of UNC5C can effectively inhibit the proliferation potential of renal cancer cells. Promoter DNA methylation, chromatin remodeling-mediated epigenetic regulation, transcriptional inhibition, RNA-binding protein and miRNA-mediated post-transcriptional inhibition, genetic changes caused by deep deletion and truncated mutations, and ubiquitinating enzyme-mediated protein degradation can synergistically cause the down-regulation of UNC5C expression in solid tumors. This study is the first to analyze the comprehensive molecular mechanism of down-regulation of the tumor suppressor gene UNC5C from multiple dimensions using pan-cancer data. Our results suggest that analyses of gene expression regulation relying on computational biological methods may help guide the targeted therapy of tumor suppressor gene reactivation.
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Biologia Computacional/métodos , Regulação para Baixo/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Redes Reguladoras de Genes/fisiologia , Receptores de Netrina/genética , Receptores de Netrina/metabolismo , Linhagem Celular Tumoral , Humanos , Análise de Sequência de RNA/métodosRESUMO
Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo. The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO2 (Cr/CeO2) nanozyme increases the reduced Ce3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO2. Furthermore, Cr/CeO2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.
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Lesões Encefálicas Traumáticas/tratamento farmacológico , Catálise/efeitos dos fármacos , Cério/administração & dosagem , Compostos de Cromo/administração & dosagem , Oxirredução/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taxa de Sobrevida , Cicatrização/efeitos dos fármacosRESUMO
Hexokinase (HK) plays a key role in various biological processes such as glycolysis of tumor cells. However, there is still a lack of systematic understanding of the contribution of HK family genes in different types of cancer. In the present study, we systematically analyzed the molecular changes and clinical correlations of HK family genes in 33 types of cancer extracted from more than 10,000 subjects. As a result, there were extensive genetic changes in HK family genes and the expression levels of HK family were significantly correlated with the activity of cancer marker-related pathways. In addition, HK family genes may be useful in predicting prognosis and therapeutic efficacy. Moreover, HK1,HK2 and HK3 may become potential oncogenes across a variety of cancer types. Furthermore, the oncogenic functions of HK1 in bladder cancer have been confirmed in vitro. Collectively, our results provide valuable resources to guide the mechanism and therapeutic analysis concerning the role of HK family genes in cancer.
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Biomarcadores Tumorais/genética , Carcinogênese/genética , Redes Reguladoras de Genes/fisiologia , Hexoquinase/genética , Neoplasias/genética , Oncogenes/fisiologia , Biomarcadores Tumorais/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Hexoquinase/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Atomically precise Au25(SG)18 clusters have shown great promise in near-infrared II cerebrovascular imaging, X-ray imaging, and cancer radiotherapy due to their high atomic number, unique molecular-like electronic structure, and renal clearable properties. Therefore, it is important to study the in vivo toxicity of Au25 clusters. Unfortunately, previous toxicological investigations focused on low injected doses (<100 mg kg-1) and routine research methods, such as blood chemistry and biochemistry, which cannot reflect neurotoxicity or tiny changes in neural activity. In this work, in vivo neuroelectrophysiology of Au25 clusters at ultrahigh injected doses (200, 300, and 500 mg kg-1) was investigated. Local field potential showed that the Au25-treated mice showed a spike in delta rhythm and moved to lower frequency over time. The power spectrum showed a 38.3% reduction in the peak value at 10 h post-injection of Au25 clusters compared with 3 h post-injection, which gradually became close to the normal level, indicating no permanent damage to the nervous system. Moreover, no significant structural changes were found in both neurons and glial cells at the histological level. These results of in vivo neuroelectrophysiology will encourage scientists to make more exciting discoveries on nervous system diseases by employing Au25 clusters even at ultrahigh injected doses.