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Deciphering the mechanisms of charge storage on carbon-based materials is pivotal for the development of next-generation electrochemical energy storage systems. Graphene, the building block of graphitic electrodes, is an ideal model for probing such processes on a fundamental level. Herein, we investigate the thermodynamics of the graphene/aqueous electrolyte interface by utilizing a multiscale quantum mechanics-classical molecular dynamics (QM/MD) approach to provide insights into the effect of alkali metal ion (Li+) concentration on the interfacial tension (γSL) of the charged graphene/electrolyte interface. We demonstrate that the dependence of γSL on the applied surface charge exhibits an asymmetric behavior relative to the neutral surface. At the positively charged graphene sheet, the electrowetting response is amplified by electrolyte concentration, resulting in a strongly hydrophilic surface. On the contrary, at negative potential bias, γSL shows a weaker response to the charging of the electrode. Changes in γSL greatly affect the total areal capacitance predicted by the Young-Lippmann equation but have a negligible impact on the simulated total areal capacitance, indicating that the EDL structure is not directly correlated with the wettability of the surface and different interfacial mechanisms drive the two phenomena. The proposed model is validated experimentally by studying the electrowetting response of highly oriented pyrolytic graphite over a wide range of electrolyte concentrations. Our work presents the first combined theoretical and experimental study on electrowetting using carbon surfaces, introducing new conceptual routes for the investigation of wetting phenomena under potential bias.
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Cephalexin, a first-generation cephalosporin, is the first-line oral therapy for children with musculoskeletal infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Cefadroxil, a similar first-generation cephalosporin, is an attractive alternative to cephalexin given its longer half-life. In this study, we describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of cephalexin and cefadroxil in children with musculoskeletal infections. Children aged 6 months to 18 years with a musculoskeletal infection were enrolled in a prospective, open-label, crossover PK study and given single oral doses of cefadroxil (50-75 mg/kg up to 2,000 mg) and cephalexin (50 mg/kg up to 1,375 mg). Population PK models were developed and used for dosing simulations. Our primary PD target was the achievement of free antibiotic concentrations above the minimum inhibitory concentration (fT >MIC) for 40% of the day for MICs ≤ 4 mg/L. PK of cephalexin (n = 15) and cefadroxil (n = 14) were best described using a one-compartment, first-order absorption model, with a lag time component for cefadroxil. PK parameters were notable for cefadroxil's longer half-life (1.61 h) than cephalexin's (1.10 h). For pediatric weight bands, our primary PD target was achieved by cephalexin 25 mg/kg/dose, maximum 750 mg/dose, administered three times daily and cefadroxil 40 mg/kg/dose, maximum 1,500 mg/dose, administered twice daily. More aggressive dosing was required to achieve higher PD targets. Among children with musculoskeletal infections, oral cephalexin and cefadroxil achieved PD targets for efficacy against MSSA. Given less frequent dosing, twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy for serious infections due to MSSA.
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Antibacterianos , Cefadroxila , Cefalexina , Estudos Cross-Over , Testes de Sensibilidade Microbiana , Cefalexina/farmacocinética , Cefalexina/uso terapêutico , Humanos , Criança , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Cefadroxila/farmacocinética , Cefadroxila/uso terapêutico , Feminino , Masculino , Pré-Escolar , Adolescente , Lactente , Estudos Prospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
MC1R (melanocortin 1 receptor) encodes the melanocortin-1 receptor, which can activate intracellular cAMP synthesis under the stimulation of the α-melanocyte stimulating hormone (α-MSH) ligand. Increased cAMP then activates the protein kinase A (PKA) pathway, resulting in the up-regulation of the expression of the microphthalmia-associated transcription factor (MITF) which is a critical regulatory factor of melanin synthesis, and tyrosinase (TYR), the rate-limiting enzyme of melanin synthesis tyrosinase (TYR), and ultimately affects production of eumelanin and pheomelanin, and the coat color phenotype of mammalian species. Previous reports have indicated that the mutation A243T in the transmembrane domain 6 (TM6) of MC1R protein might disrupt the function of MC1R, contributing to the red phenotype in Duroc pig. However, functional analysis of the A243T mutation in MC1R has not yet been carried out. In this study, we attempted to used single-stranded oligo-deoxyribonucleotides (ssODN) as donor templates to introduce the c.727G>A (A243T) mutation into MC1R in human melanoma cell line SK-MEL-2 by CRISPR/Cas9 to analyze its effects on MC1R functions. We found the occurrence of ssODN recombination reached to 10%. Unfortunately, Sanger sequencing MC1R in six single-cell clones revealed that none carried the c.727G>A mutation, but all carried undesired mutations surrounding the target site. Cells transfected with CRISPR/Cas9 plasmids and ssODN presented significantly attenuated cAMP activation, and down-regulated MITF and TYR expression, indicating that the editing MC1R could affect the melanin synthesis function in cells. This study provides a basis for further investigation the mechanism of MC1R mutation on animal coat color.
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Melanoma , Receptor Tipo 1 de Melanocortina , Animais , Sistemas CRISPR-Cas , Humanos , Mamíferos/metabolismo , Melaninas/genética , Melanoma/genética , Melanoma/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Receptor Tipo 1 de Melanocortina/genética , Receptor Tipo 1 de Melanocortina/metabolismo , SuínosRESUMO
As a widely known plant hormone, Abscisic acid plays an important role in the progress of planting cell and their stress response. Recently, we reported that ABA might play an anti-cancer role in glioma tissues. In the present study, the molecular mechanism of ABA anti-cancer was further explored in glioblastoma cells. By measuring LC3 puncta formation and conversion in glioblastoma cells, inhibiting the autophagic pathway, targeting the essential autophagic modulator beclin 1 with RNA interference, and analysing cellular morphology via transmission electron microscopy, we found that ABA-treated glioblastoma cells exhibited the features of autophagy. Specifically, ABA-induced autophagy in glioblastoma cells was mediated by the MAPK/JNK signalling pathway rather than the PI3K/AKT/mTOR axis. Moreover, the inhibition or knockdown of JNK specifically blocked ABA-induced autophagic cell death. ABA-induced autophagy was further confirmed in tumour-bearing mice and was accompanied by the inhibition of glioma growth in vivo. This report is the first to describe autophagy induced by ABA and mediated by the MAPK/JNK pathway in human cancer cells and tumour-bearing mice. These results may shed some light in new therapeutic strategies of glioma.
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Ácido Abscísico/farmacologia , Autofagia , Glioblastoma/enzimologia , Glioblastoma/patologia , Sistema de Sinalização das MAP Quinases , Aloenxertos/efeitos dos fármacos , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Vacúolos/ultraestruturaRESUMO
PURPOSE: This study was conducted to explore the cerebellar substructure volumetric alterations in refractory unilateral temporal lobe epilepsy (TLE) patients and the relationship with clinical factors and cognitive scores. METHODS: A total of 48 unilateral refractory TLE patients and 48 age- and gender-matched normal controls (NCs) were retrospectively studied. All subjects underwent high-resolution magnetic resonance imaging (MRI) and automatically segmented volumetric brain information was obtained using volBrain and Data Processing Assistant for Resting-State fMRI (DPARSF) separately. Clinical seizure features and cognitive scores were acquired by a structured review of medical records. RESULTS: The total volumes (TVs) of bilateral crus I, crus II, and IX were significantly smaller in the refractory unilateral TLE epilepsy patients. The gray matter volumes (GMVs) of cerebellar lobules showed lateralized reduction in ipsilateral III, IX, and contralateral crus II. Contralateral crus II GMV showed significant negative correlation with the duration of epilepsy (râ¯=â¯-0.31, pâ¯=â¯0.035) and positive association with the cognitive scores including long-term memory (LTM) (râ¯=â¯0.39, pâ¯=â¯0.017), short-term memory (STM) (râ¯=â¯0.51, pâ¯=â¯0.001) verbal comprehension index (VCI) (râ¯=â¯0.37, pâ¯=â¯0.024), and perceptual organization index (POI) (râ¯=â¯0.36, pâ¯=â¯0.030). The voxel-based morphometry (VBM) analysis proved similar results. The contralateral crus I GMV was significantly smaller in the generalized onset group (tâ¯=â¯2.536, pâ¯=â¯0.015). CONCLUSIONS: The lobules of the cerebellar in refractory TLE patients manifest different volumetric change characteristics. Crus II contralateral GMV is negatively correlated with the duration of epilepsy and positively associated with the cognitive scores.
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Epilepsia do Lobo Temporal , Cerebelo/diagnóstico por imagem , Cognição , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
OBJECTIVE: Exploring the role of amygdala enlargement (AE) in temporal lobe epilepsy (TLE) without ipsilateral mesial temporal sclerosis (MTS) using comprehensive presurgical workup tools including traditional tools, automatically volumetric analysis, high-density EEG (HD-EEG) source imaging (HD-ESI), and stereoelectroencephalography (SEEG). METHODS: Nine patients diagnosed with TLE-AE who underwent resective surgeries encompassing the amygdala were retrospectively studied. HD-ESI was obtained using 256-channel HD-EEG on the individualized head model. For automatic volumetric analysis, 48 matched controls were enrolled. Diagnosis and surgical strategies were based on a comprehensive workup following the anatomo-electro-clinical principle. RESULTS: At post-operative follow-up (average 30.9 months), eight patients had achieved Engel class I and one Engel class II recovery. HD-ESI yielded unifocal source estimates in anterior mesial temporal region in 85.7% of cases. Automatic volumetric analysis showed the AE sides were consistent with the values determined through other preoperative workup tools. Furthermore, the amygdala volume of the affected sides in AE was significantly greater than that of the larger sides in controls (p < 0.001). Meanwhile, the amygdala volume lateral index (LI) of AE was significantly higher than in controls (p < 0.001). SEEG analysis showed that ictal onsets arose from the enlarged amygdala (and hippocampus) in all cases. CONCLUSION: In addition to traditional workup tools, automatic volumetric analysis, HD-ESI on individualized head model, and invasive SEEG can provide evidence of epileptogenicity in TLE-AE. Resective surgical strategies encompassing the amygdala result in better prognosis. In suspected TLE cases, more attention should be focused on detecting enlargement of amygdala which sometimes is "hidden" in "MR-negative" non-MTS cases.
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Epilepsia do Lobo Temporal , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/cirurgia , Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Hipocampo , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Lobo TemporalRESUMO
Myostatin (MSTN), a member of the transforming growth factor-ß superfamily, is a negative regulator of muscle growth and development. Disruption of the MSTN gene in various mammalian species markedly promotes muscle growth. Previous studies have mainly focused on the disruption of the MSTN peptide coding region in pigs but not on the modification of the signal peptide region. In this study, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system was used to successfully introduce two mutations (PVD20H and GP19del) in the MSTN signal peptide region of the indigenous Chinese pig breed, Liang Guang Small Spotted pig. Both mutations in signal peptide increased the muscle mass without inhibiting the production of mature MSTN peptide in the cells. Histological analysis revealed that the enhanced muscle mass in MSTN+/PVD20H pig was mainly due to an increase in the number of muscle fibers. The expression of MSTN in the longissimus dorsi muscle of MSTN+/PVD20H and MSTNKO/PVD20H pigs was significantly downregulated, whereas that of myogenic regulatory factors, including MyoD, Myogenin, and Myf-5, was significantly upregulated when compared to those in the longissimus dorsi muscle of wild-type pigs. Meanwhile, the mutations also activated the PI3K/Akt pathway. The results of this study indicated that precise editing of the MSTN signal peptide can enhance porcine muscle development without markedly affecting the expression of mature MSTN peptide, which could exert other beneficial biological functions in the edited pigs.
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Animais Geneticamente Modificados/genética , Sistemas CRISPR-Cas , Edição de Genes , Desenvolvimento Muscular , Músculo Esquelético/citologia , Miostatina/genética , Sinais Direcionadores de Proteínas/genética , Animais , Animais Geneticamente Modificados/crescimento & desenvolvimento , Masculino , Miostatina/antagonistas & inibidores , SuínosRESUMO
Cu2+ are found to greatly reduce the photoinduced oxidase activity of fluorescein and then inhibit the chromogenic reaction catalyzed by fluorescein. A simple colorimetric assay for Cu2+ is established. Based on this, bifunctional nanocomposites of α-fetoprotein (AFP) antibody (Ab) and copper-based metal-organic framework (Ab2@Cu-MOF) are synthesized by the simple self-assembly of AFP Ab2, Cu2+, and 4,4'-dipyridyl: the binding site of AFP Ab2 exposed on the surface of the nanocomposites can specifically recognize AFP antigen; Cu2+ in nanocomposites can inhibit the visible light-induced activity of fluorescein. The structure of Ab2@Cu-MOF disintegrate and Cu2+ is released in an acetate buffer solution. The higher the amount of AFP antigens, the more significant the inhibitory effect. Thus, the Ab2@Cu-MOF immunoassay for AFP determination is established using 3,3',5,5'-tetramethylbenzidine as chromogenic substrate with a detection limit of 35 pg.mL-1. This simple, cheap, and sensitive method sheds substantial light on practical clinical diagnosis. Meanwhile, the mechanism of inhibition is revealed to facilitate the targeted selection of enzyme regulators. Graphical abstract Diagrammatic illustration of Cu2+ detection (part a) and Ab2@Cu-MOF immunoassay for sensing α-fetoprotein based on the synthesized Ab2@Cu-MOF nanocomposites (parts a and b).
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Anticorpos Biespecíficos/imunologia , Cobre/química , Estruturas Metalorgânicas/química , Nanocompostos/química , alfa-Fetoproteínas/análise , Anticorpos Imobilizados/imunologia , Benzidinas/química , Compostos Cromogênicos/química , Colorimetria , Fluoresceína/química , Corantes Fluorescentes/química , Humanos , Imunoensaio/métodos , Limite de Detecção , Piridinas/química , alfa-Fetoproteínas/imunologiaRESUMO
Lowering the background signal for more sensitive analysis of determinands is as important as amplifying the target signal. The photoinduced oxidase of fluorescein has been reported, which can catalyze the oxidization of common substrates in a few minutes. As a metaphor for locks and keys, we designed double locks confining the activity of fluorescein to reduce the background absorbance during colorimetric detection. The first lock inhibits the main activity of fluorescein by phosphating. The second lock almost completely deactivates fluorescein by forming coordination nanoparticles (CNPs) via the self-assembly of cerium chloride and fluorescein diphosphate (FDP). The Ce-FDP CNPs are characterized by scanning electron microscope (SEM), dynamic light scattering (DLS), Fourier transform infrared spectrometer (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and energy dispersive spectrum (EDS), which show electrostatic formation and amorphous character in the morphology. Alkaline phosphatase (ALP), the key to release fluorescein, can destroy Ce-FDP CNPs along with decomposing FDP by degrading phosphate groups. Therefore, a novel colorimetric strategy for sensitive detection of ALP is established. The detection of α-fetoprotein (AFP) is further succeeded by labeling AFP antibody with ALP. By dramatically reducing the background absorbance, the detection limits of ALP and AFP are as low as 0.014 mU/mL and 0.023 ng/mL, respectively. This convenient, brief, sensitive assay provides a promising prospect for clinical diagnosis. Graphical abstract.
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Fosfatase Alcalina/sangue , Colorimetria/métodos , Imunoensaio/métodos , alfa-Fetoproteínas/análise , Fosfatase Alcalina/química , Anticorpos Imobilizados/imunologia , Benzidinas/química , Catálise , Cério/química , Compostos Cromogênicos/química , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Oxirredução , alfa-Fetoproteínas/imunologiaRESUMO
The nanopore technique employs a nanoscale cavity to electrochemically confine individual molecules, achieving ultrasensitive single-molecule analysis based on evaluating the amplitude and duration of the ionic current. However, each nanopore sensing interface has its own intrinsic sensing ability, which does not always efficiently generate distinctive blockade currents for multiple analytes. Therefore, analytes that differ at only a single site often exhibit similar blockade currents or durations in nanopore experiments, which often produces serious overlap in the resulting statistical graphs. To improve the sensing ability of nanopores, herein we propose a novel shapelet-based machine learning approach to discriminate mixed analytes that exhibit nearly identical blockade current amplitudes and durations. DNA oligomers with a single-nucleotide difference, 5'-AAAA-3' and 5'-GAAA-3', are employed as model analytes that are difficult to identify in aerolysin nanopores at 100 mV. First, a set of the most informative and discriminative segments are learned from the time-series data set of blockade current signals using the learning time-series shapelets (LTS) algorithm. Then, the shapelet-transformed representation of the signals is obtained by calculating the minimum distance between the shapelets and the original signals. A simple logistic classifier is used to identify the two types of DNA oligomers in accordance with the corresponding shapelet-transformed representation. Finally, an evaluation is performed on the validation data set to show that our approach can achieve a high F1 score of 0.933. In comparison with the conventional statistical methods for the analysis of duration and residual current, the shapelet-transformed representation provides clearly discriminated distributions for multiple analytes. Taking advantage of the robust LTS algorithm, one could anticipate the real-time analysis of nanopore events for the direct identification and quantification of multiple biomolecules in a complex real sample (e.g., serum) without labels and time-consuming mutagenesis.
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DNA/química , Nanoporos , Algoritmos , Toxinas Bacterianas/química , Sequência de Bases , Nucleotídeos/química , Proteínas Citotóxicas Formadoras de Poros/químicaRESUMO
Hippocampus is a critical component of the central nervous system. SRSF10 is expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in hippocampus development is unknown. In this study, using SRSF10 conditional knock-out mice in neural progenitor cells (NPCs), we found that dysfunction of SRSF10 leads to developmental defects in the dentate gyrus of hippocampus, which manifests as the reduced length and wider suprapyramidal blade and infrapyramidal blade.Furthermore, we proved that loss of SRSF10 in NPCs caused inhibition of the differentiation activity and the abnormal migration of NPCs and granule cells, resulting in reduced granule cells and more ectopic granule cells dispersed in the molecular layer and hilus. Finally, we found that the abnormal migration may be caused by the radial glia scaffold and the reduced DISC1 expression in NPCs. Together, our results indicate that SRSF10 is required for the cell migration and formation of dentate gyrus during the development of hippocampus.
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Movimento Celular , Giro Denteado , Camundongos Knockout , Células-Tronco Neurais , Fatores de Processamento de Serina-Arginina , Animais , Células-Tronco Neurais/metabolismo , Giro Denteado/metabolismo , Movimento Celular/fisiologia , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Neurônios/metabolismo , Hipocampo/metabolismo , Camundongos , Neurogênese/fisiologia , Diferenciação Celular/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Camundongos Endogâmicos C57BLRESUMO
The excessive emission of CO2 has aroused increasingly serious environmental problems. Electrochemical CO2 reduction reaction (CO2RR) is an effective way to reduce CO2 concentration and simultaneously produce highly valued chemicals and fuels. Cuδ+ species are regarded as promising active sites to obtain multi-carbon compounds in CO2RR, however, they are easily reduced to Cu0 during the reaction and fail to retain the satisfying selectivity for C2+ products. Herein, via a one-step method, we synthesize Cu2(OH)2CO3 microspheres composed of nanosheets, which has achieved a superior Faraday efficiency for C2+ products as high as 76.29 % at -1.55â V vs. RHE in an H cell and 78.07 % at -100â mA cm-2 in a flow cell. Electrochemical measurements, inâ situ Raman spectra and attenuated total reflectance infrared spectra (ATR-IR) as well as the theoretic calculation unveil that, compared with Cu(OH)2 and CuO, the dual O-containing anionic groups (OH- and CO3 2-) in Cu2(OH)2CO3 can effectively stabilize the Cuδ+ species, promote the adsorption and activation of CO2, boost the coverage of *CO and the coupling of *CO-*COH, thus sustain the flourishment of C2+ products.
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Objective: To evaluate the effectiveness of combined resection and radiotherapy (CRAR) for the treatment of primary pineal malignant melanoma (PPMM). Methods: Relevant studies were identified through a literature search in PubMed, Embase, and Web of Science from 1899 to September 1, 2023. Then we further screened the literature according to the updated PRISMA 2020 guidelines. The article information, patient information, treatment, and survival rate were analyzed. The primary outcome measures the survival rate of CRAR compared with the overall patients and the patients without treatment. Secondary outcome measures operation methods, radiotherapy methods, and dose. Results: In total, 28 published articles were recorded. Among them, 35.71% (10/28) articles were on CRAR. The median overall survival, CRAR, and no treatment survival were 65, 88, and 12 weeks, respectively. The median overall survival of CRAR was demonstrably better than that of no treatment (p < 0.0001) and overall survival, even with p = 0.1177. Most of the operations adopted a supracerebellar infratentorial approach, and stereotactic radiation to tumor bed usually ranged between 50 and 60 Gy. Small dose and multiple fractions was the most popular radiotherapy method. Conclusion: Currently, CRAR, compared with other treatments, is more beneficial to prolonging the survival of PPMM patients. However, many more clinical cases are needed to verify it as the best treatment approach.
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Minimally invasive ablation has been widely applied for treatment of various solid tumors, including hepatocellular carcinoma, renal cell carcinoma, breast carcinomas, etc. In addition to removing the primary tumor lesion, ablative techniques are also capable of improving the anti-tumor immune response by inducing immunogenic tumor cell death and modulating the tumor immune microenvironment, which may be of great benefit to inhibit the recurrent metastasis of residual tumor. However, the short-acting activated anti-tumor immunity of post-ablation will rapidly reverse into an immunosuppressive state, and the recurrent metastasis owing to incomplete ablation is closely associated with a dismal prognosis for the patients. In recent years, numerous nanoplatforms have been developed to improve the local ablative effect through enhancing the targeting delivery and combining it with chemotherapy. Particularly, amplifying the anti-tumor immune stimulus signal, modulating the immunosuppressive microenvironment, and improving the anti-tumor immune response with the versatile nanoplatforms have heralded great application prospects for improving the local control and preventing tumor recurrence and distant metastasis. This review discusses recent advances in nanoplatform-potentiated ablation-immune synergistic tumor therapy, focusing on common ablation techniques including radiofrequency, microwave, laser, and high-intensity focused ultrasound ablation, cryoablation, and magnetic hyperthermia ablation, etc. We discuss the advantages and challenges of the corresponding therapies and propose possible directions for future research, which is expected to provide references for improving the traditional ablation efficacy.
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Objective: We designed a novel intraoperative malleable adjustable continuous suction tube to obtain clear surgical fields, reduce intracranial pressure, and lower the temperature of the surgical area. Methods: This device consists of six parts: continuous suction tube head and cotton patty, suction tube, fixed wire position, fixed clip, spiral plastic pressure regulating valve, and tail. It can continuously extract blood, cerebrospinal fluid, and rinsing solution from surgical fields, with minimal contact and trauma to tissues, nerves, and blood vessels, while also having a negligible impact on the surgeon's focus and procedure. Result: The excellent and safe performance (simple, malleable, adjustable, space-saving, inexpensive, safe, and effective) of this device in clearing the operating field has been proven in more than 2000 neurosurgical operative procedures. We encountered no complications associated with this device, such as cerebral hematoma, postoperative low intracranial pressure, or vascular and nerve injuries. Conclusion: The newly innovated intraoperative malleable adjustable continuous suction tube is effective and safe for microneurosurgery.
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Imaging-guided percutaneous microwave thermotherapy has been regarded as an important alternative nonsurgical therapeutic strategy for hepatocellular carcinoma (HCC) that provides excellent local tumor control and favorable survival benefit. However, providing a high-resolution, real-time, and noninvasive imaging technique for intraoperative guidance and controlling postoperative residual tumor recurrence are urgent needs for the clinical setting. In this study, a cisplatin (CDDP)-loaded nanocapsule (NPs@CDDP) with microwave responsive property was prepared to simultaneously serve as a contrast agent of emerging thermoacoustic imaging and a sensitizing agent of microwave thermo-chemotherapy. Accompanying the enzymolysis in the tumor microenvironment, the NPs@CDDP responsively release l-arginine (l-Arg) and CDDP. l-Arg with excellent microwave-absorbing property allowed it to serve as a thermoacoustic imaging contrast agent for accurately delineating the tumor and remarkably increasing tumor temperature under ultralow power microwave irradiation. Apart from the chemotherapeutic effect, CDDP elevated the intracellular H2O2 level through cascade reactions and further accelerated the continuous transformation of l-Arg to nitric oxide (NO), which endowed the NPs@CDDP with NO-generation capability. Notably, the high concentration of intracellular NO was proved to aggravate lipid peroxidation and greatly improved the efficacy of microwave thermo-chemotherapy. Thereby, NPs@CDDP was expected to serve as a theranostic agent integrating the functions of tumor microenvironment-responsive drug delivery system, contrast agent of thermoacoustic imaging, thermal sensitizing agent, and NO nanogenerator, which was promising to provide a potential imaging-guided therapeutic strategy for HCC.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Óxido Nítrico/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Micro-Ondas , Meios de Contraste/uso terapêutico , Peróxido de Hidrogênio , Cisplatino/uso terapêutico , Antineoplásicos/uso terapêutico , Microambiente TumoralRESUMO
Alternative pre-mRNA splicing plays critical roles in brain development. SRSF10 is a splicing factor highly expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in neural development is unclear. In this study, by conditional depleting SRSF10 in neural progenitor cells (NPCs) in vivo and in vitro, we found that dysfunction of SRSF10 leads to developmental defects of the brain, which manifest as abnormal ventricle enlargement and cortical thinning anatomically, as well as decreased NPCs proliferation and weakened cortical neurogenesis histologically. Furthermore, we proved that the function of SRSF10 on NPCs proliferation involved the regulation of PI3K-AKT-mTOR-CCND2 pathway and the alternative splicing of Nasp, a gene encoding isoforms of cell cycle regulators. These findings highlight the necessity of SRSF10 in the formation of a structurally and functionally normal brain.
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Magneto-optical isolators are key components in photonic systems. Despite the progress of silicon-integrated optical isolators, the Faraday rotation of silicon-integrated magneto-optical materials, such as cerium-doped yttrium iron garnet (Ce:YIG), show a strong temperature dependence, limiting the temperature range for integrated nonreciprocal photonic device applications. In this work, we report dysprosium substituted Ce:YIG thin films (Dy2Ce1Fe5O12, Dy:CeIG) showing a low temperature coefficient of Faraday rotation. A temperature insensitive range of the Faraday rotation is observed in between 25 °C to 70 °C for this material, compared to 20% variation of the Faraday rotation in Ce:YIG thin films. A Dy:CeIG based temperature insensitive silicon-integrated optical isolator operating in the temperature range of 23 °C to 70 °C is experimentally demonstrated.
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Graphene-based nanochannels are a popular choice in emerging nanofluidics applications because of their tunable and nanometer-scale channels. In this work, molecular dynamics (MD) simulations were employed both to (i) assess the stability of dry and hydrated graphene nanochannels and (ii) elucidate the properties of water confined in these channels, using replica-scale models with 0.66-2.38 nm channel heights. The use of flexible nanochannel walls allows the nanochannel height to relax in response to the solvation forces arising from the confined fluid and the forces between the confining surfaces, without the need for application of arbitrarily high external pressures. Dry nanochannels were found to completely collapse if the initial nanochannel height was less than 2 nm, due to attractive van der Waals interactions between the confining graphene surfaces. However, the presence of water was found to prevent total nanochannel collapse, due to repulsive hydration forces opposing the attractive van der Waals force. For nanochannel heights less than â¼1.7 nm, the confining surfaces must be relaxed to obtain accurate hydration pressures and water diffusion coefficients, by ensuring commensurability between the number of confined water layers and the channel height. For very small (â¼0.7 nm), hydrated channels a pressure of 231 MPa due to the van der Waals forces was obtained. In the same system, the confined water forms a mobile, liquid monolayer with a diffusion coefficient of 4.0 × 10-5 cm2 s-1, much higher than bulk liquid water. Although this finding conflicts with most classical MD simulations, which predict in-plane order and arrested dynamics, it is supported by experiments and recently published first-principles MD simulations. Classical simulations can therefore be used to predict the properties of water confined in sub-nanometre graphene channels, providing sufficiently realistic molecular models and accurate intermolecular potentials are employed.
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Based on alterations in gene expression associated with the production of glycolysis and cholesterol, this research classified glioma into prognostic metabolic subgroups. In this study, data from the CGGA325 and The Cancer Genome Atlas (TCGA) datasets were utilized to extract single nucleotide variants (SNVs), RNA-seq expression data, copy number variation data, short insertions and deletions (InDel) mutation data, and clinical follow-up information from glioma patients. Glioma metabolic subtypes were classified using the ConsensusClusterPlus algorithm. This study determined four metabolic subgroups (glycolytic, cholesterogenic, quiescent, and mixed). Cholesterogenic patients had a higher survival chance. Genome-wide investigation revealed that inappropriate amplification of MYC and TERT was associated with improper cholesterol anabolic metabolism. In glioma metabolic subtypes, the mRNA levels of mitochondrial pyruvate carriers 1 and 2 (MPC1/2) presented deletion and amplification, respectively. Differentially upregulated genes in the glycolysis group were related to pathways, including IL-17, HIF-1, and TNF signaling pathways and carbon metabolism. Downregulated genes in the glycolysis group were enriched in terpenoid backbone biosynthesis, nitrogen metabolism, butanoate metabolism, and fatty acid metabolism pathway. Cox analysis of univariate and multivariate survival showed that risks of glycolysis subtypes were significantly higher than other subtypes. Those results were validated in the CGGA325 dataset. The current findings greatly contribute to a comprehensive understanding of glioma and personalized treatment.