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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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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
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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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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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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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
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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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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Despite the importance of timing in our daily lives, our understanding of how the human brain mediates second-scale time perception is limited. Here, we combined intracranial stereoelectroencephalography (SEEG) recordings in epileptic patients and circuit dissection in mice to show that visual cortex (VC) encodes timing information. We first asked human participants to perform an interval-timing task and found VC to be a key timing brain area. We then conducted optogenetic experiments in mice and showed that VC plays an important role in the interval-timing behavior. We further found that VC neurons fired in a time-keeping sequential manner and exhibited increased excitability in a timed manner. Finally, we used a computational model to illustrate a self-correcting learning process that generates interval-timed activities with scalar-timing property. Our work reveals how localized oscillations in VC occurring in the seconds to deca-seconds range relate timing information from the external world to guide behavior.
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Percepção do Tempo , Córtex Visual , Humanos , Camundongos , Animais , Neurônios/fisiologia , Córtex Visual/fisiologia , Percepção do Tempo/fisiologia , Aprendizagem , Fatores de TempoRESUMO
Photodynamic therapy (PDT) is a promising alternative and palliative therapeutic strategy for colorectal cancer (CRC). A novel photosensitizer with higher selectivity for CRC and fewer side effects is vital for clinical application. Given that the overexpression of hydrogen sulfide (H2S) in CRC, it is expected to provide a selective stimulus for activatable photosensitizers that in respond to the specific microenvironment. Herein, we report a novel development of metal-organic frameworks (MOFs) composed of meso-Tetra (4-carboxyphenyl) porphine (TCPP) and ferric ion (Fe3+) through a facile one-pot process. Experiments both in vitro and in vivo reveal that the MOF is capable of depredating in response to the high content of H2S in tumor microenvironment of CRC. Accompanying with the degradation and release of TCPP, the fluorescence and photosensitivity effect is switched from "off" to "on", enabling the MOF to serve as a H2S activatable nano-photosensitizer for real-time fluorescence imaging-guided and targeted PDT of CRC.
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The utilization of solar energy for CO2 conversion not only enables a green and low-carbon recycling of CO2 with renewable energy, but also solves ecological problems. BixMOy (M = V, Mo, W) materials have typical layered structures and unique electronic properties that provide suitable band gaps and potential to meet the basic conditions for CO2 reduction. However, pristine BixMOy faces with problems such as small specific surface area, insufficient active sites, low charge carriers' separation and utilization efficiency. This review comprehensively described the basic principles and reaction pathways of photocatalytic CO2 reduction, and further presented the research progress of BixMOy catalysts in CO2 conversion reactions. In this perspective, we further focus on the design concepts and modification strategies to improve the photocatalytic CO2 reduction activity of BixMOy, such as morphology control, constructing surface vacancies and heterojunction fabrication. Finally, based on representative researches, the present review will be expected to provide updated information and insights for developing advanced BixMOy materials to further improve CO2 reduction activity and selectivity.
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Base editing technology is being increasingly applied in genome engineering, but the current strategy for designing guide RNA (gRNA) relies substantially on empirical experience rather than a dependable and efficient in silico design. Furthermore, the pleiotropic effect of base editing on disease treatment remains unexplored, which prevents its further clinical usage. Here, we presented BExplorer, an integrated and comprehensive computational pipeline to optimize the design of gRNAs for 26 existing types of base editors in silico. Using BExplorer, we described its results for two types of mainstream base editors, BE3 and ABE7.10, and evaluated the pleiotropic effect of the corresponding base editing loci. BExplorer revealed 524 and 900 editable pathogenic Single Nucleotide Polymorphism (SNP) loci in the human genome together with the selected optimized gRNAs for BE3 and ABE7.10, respectively. In addition, the impact of 707 edited pathogenic SNP loci following base editing on 151 diseases was systematically explored by revealing their pleiotropic effects, indicating that base editing should be carefully utilized given the potential pleiotropic effects. Collectively, the systematic exploration of optimized base editing gRNA design and the corresponding pleiotropic effects with BExplorer provides a computational basis for applying base editing in disease treatment.
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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
OBJECTIVE: To retrospectively analyze radiotherapy (RT) regimens for patients with high-risk neuroblastoma (HRNB) at the primary site after surgery, and to further analyze the characteristics of patients who would benefit more from RT. METHODS: 98 pediatric patients with HRNB were analyzed for local control (LC), RT dose, extent of excision and prognostic factors. Among them, 69 children received RT. RESULTS: The 3 year LC rates were 96.9 and 62.1% (p < 0.001) in the RT and non-RT groups, respectively. In the non-RT group, LC was better in patients with complete macroscopic resection (CME) than in those with incomplete macroscopic resection (IME) (p = 0.026), while in the RT group, no significant difference in LC was found (p = 0.985). Among patients with IME, the LC was 100% in patients with RT doses >= 36 Gy and 66.7% in patients with doses <36 Gy. CONCLUSION: RT is valuable, provides patients with excellent LC, and is safe in the short term. RT had a complementary therapeutic effect on incompletely resected tumors, thus bringing their LC to the level of patients with CME. For patients with IME, RT at a dose of not less than 36 Gy may improve LC. ADVANCES IN KNOWLEDGE: This study analysed the role of radiotherapy in HRNB, investigated the dose of RT depending on the degree of resection, and explored the characteristics of patients who would benefit more from RT.
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Neuroblastoma , Radioterapia (Especialidade) , Criança , Fracionamento da Dose de Radiação , Humanos , Neuroblastoma/radioterapia , Neuroblastoma/cirurgia , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
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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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.
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Neoplasias Encefálicas/classificação , Glioma/classificação , Algoritmos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Colesterol/biossíntese , Colesterol/genética , Biologia Computacional , Bases de Dados Genéticas/estatística & dados numéricos , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Glicólise/genética , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Doxorubicin (DOX) is a widely used first-line antitumor agent; however, acquired drug resistance and side effects have become the main challenges to effective cancer therapy. Herein, DOX is loaded into iron-rich metal-organic framework/tannic acid (TA) nanocomplex to form a tumor-targeting and acid-activatable drug delivery system (MOF/TA-DOX, MTD). Under the acidic tumor microenvironment, MTD simultaneously releases DOX and ferrous ion (Fe2+) accompanied by degradation. Apart from the chemotherapeutic effect, DOX elevates the intracellular H2O2 levels through cascade reactions, which will be beneficial to the Fenton reaction between the Fe2+ and H2O2, to persistently produce hydroxyl radicals (â¢OH). Thus, MTD efficiently mediates chemodynamic therapy (CDT) and remarkably enhances the sensitivity of chemotherapy. More encouragingly, the cancer cell killing efficiency of MTD is up to ~86% even at the ultralow equivalent concentration of DOX (2.26 µg/mL), while the viability of normal cells remained >88% at the same concentration of MTD. Taken together, MTD is expected to serve as drug-delivery nanoplatforms and â¢OH nanogenerators for improving chemo/chemodynamic synergistic therapy and reducing the toxic side effects.
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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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Oxidative stress is becoming increasingly implicated in the development of a variety of neurological disorders. However, the underlying mechanism remains elusive. In the present study, we investigated the function and related signal pathway which Cpg15, a neuronal-specific expressed neurotrophic factor, plays in the oxidative stress of neurons using a H2O2-treated N2a cell model. The results showed that the Cpg15 expression was decreased under oxidative stress, and overexpression of Cpg15 increased the activity of antioxidative SOD enzymes and decreased the expression level of prooxidative COX2 enzyme, and the level of oxidative products malondialdehyde (MDA), indicating its function and potential mechanism in alleviating the oxidative stress of cells. The results also indicated that the Nrf2/HO-1 antioxidative pathway was involved in the Cpg15-mediated alleviation of oxidative stress. Also, overexpression of Cpg15 activated the Nrf2 antioxidative pathway in the thalamus of the REM sleep-deprived mice. In conclusion, our results implied that supplemental expression of Cpg15 may alleviate oxidative stress in neuronal cells via regulating the redox enzymes or activating the Nrf2 antioxidant pathway.