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Bone metastasis is a type of metastatic tumors that involves the spreads of malignant tumor cells into skeleton, and its diagnosis and treatment remain a big challenge due to the unique tumor microenvironment. We herein develop osteoclast and tumor cell dual-targeting biomimetic semiconducting polymer nanocomposites (SPFeNOC ) for amplified theranostics of bone metastasis. SPFeNOC contain semiconducting polymer and iron oxide (Fe3 O4 ) nanoparticles inside core and surface camouflaged hybrid membrane of cancer cells and osteoclasts. The hybrid membrane camouflage enables their targeting to both metastatic tumor cells and osteoclasts in bone metastasis through homologous targeting mechanism, thus achieving an enhanced nanoparticle accumulation in tumors. The semiconducting polymer mediates near-infrared (NIR) fluorescence imaging and sonodynamic therapy (SDT), and Fe3 O4 nanoparticles are used for magnetic resonance (MR) imaging and chemodynamic therapy (CDT). Because both cancer cells and osteoclasts are killed synchronously via the combinational action of SDT and CDT, the vicious cycle in bone metastasis is broken to realize high antitumor efficacy. Therefore, 4T1 breast cancer-based bone metastasis can be effectively detected and cured by using SPFeNOC as dual-targeting theranostic nanoagents. This study provides an unusual biomimetic nanoplatform that simultaneously targets osteoclasts and cancer cells for amplified theranostics of bone metastasis.
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Neoplasias Ósseas , Nanocompostos , Nanopartículas , Neoplasias , Humanos , Polímeros , Medicina de Precisão , Biomimética , Nanomedicina Teranóstica/métodos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapia , Nanocompostos/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Regulation of gene expression is conducive to understanding the physiological roles of specific genes and provides therapeutic potentials, which however still remains a great challenge. Nonviral carriers have some advantages for gene delivery compared to traditional physical delivery strategies, but they often fail to control the delivery of genes in targeting regions, and thus lead to off-target side effects. Although endogenous biochemical signal-responsive carriers have been used to improve the transfection efficiency, their selectivity and specificity are still poor because of the coexistence of biochemical signals in both normal tissues and disease sites. In contrast, light-responsive carriers can be adopted to precisely control gene transgenic behaviors at the specified locations and time, thus reducing the off-target gene editing at nontarget positions. Particularly, the near-infrared (NIR) light has better tissue penetration depth and lower phototoxicity than ultraviolet and visible light sources, showing great promise for intracellular gene expression regulation. In this review, we summarize the recent progress of NIR photoresponsive nanotransducers for precision regulation of gene expression. These nanotransducers can achieve controlled gene expression via three different mechanisms (photothermal activation, photodynamic regulation, and NIR photoconversion) to allow various applications, such as gene therapy of cancer, which will be discussed in detail. A conclusion and discussion of the challenges and outlook will be given at the end of this review.
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Real-time online monitoring of volatile organic compounds (VOCs) in ambient air is crucial for timely and effective human health protection. Here, we developed an innovative, automated two-staged adsorption/thermal desorption gas chromatography/mass spectrometry (GC/MS) system for real-time online monitoring of 117 regulated volatile organic compounds (VOCs). This system comprised a sampling unit, water management trap, two-staged adsorption/thermal desorption unit, thermoelectric coolers (TECs), and a commercial GC/MS system. By implementing a micro-purge-and-trap (MP & T) step and a two-staged adsorption/thermal desorption unit, the presence of interfering substances was effectively minimized. The utilization of a heart-cutting GC, combined with a single MS detector, facilitated the precise separation and detection of 117 C2-C12 VOCs, while circumventing the identification and coelution challenges commonly associated with traditional GC-FID or GC-FID/MS methods. The performance of our newly developed online system was meticulously optimized and evaluated using standard gas mixtures. Under optimal conditions, we achieved impressive results, with R2 values ≥ 0.9946 for the standard linear curves of all 117 VOCs, demonstrating a precision (RSD) ranging from 0.2% to 6.4%. When applied in the field monitoring, the concentration drifts for 10 ppbv standard gas mixtures were 0.01-5.64% within 24 h. Our study developed a system for online monitoring of 117 atmospheric VOCs with relatively high accuracy and robustness.
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Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Adsorção , Monitoramento Ambiental/métodos , Sistemas On-Line , Gases/análiseRESUMO
A specific surface-enhanced Raman scattering (SERS) assay for dopamine (DA) based on an azo derivatization reaction is proposed for the first time by preparation of p-aminothiophenol (PATP)-modified composite SERS substrate, composed of metal-organic framework (MIL-101) decorated with Au and Ag nanoparticles. As the result, the SERS method for detection of the azo reaction between PATP and DA exhibits superior sensitivity, selectivity, and stability. A reasonable linearity in the range 10-6 to 10-10 molâL-1 is achieved, and the limit of detection is 1.2 × 10-12 molâL-1. The reactive SERS assay is free from interference in complex physiological fluid. The feasibility of the proposed SERS method for the detection of DA levels in fetal bovine serum (FBS) samples and human serum samples is validated by HPLC-MS methods, displaying promising application potential in early disease diagnosis.
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Nanopartículas Metálicas , Estruturas Metalorgânicas , Compostos de Anilina , Dopamina , Humanos , Prata , Compostos de SulfidrilaRESUMO
A novel and low-cost DNAzyme, Ni/Fe layered double hydroxide (LDH) nanosheet/G-quadruplex (without hemin) with enhanced peroxidase-mimic activity was designed. The catalytic mechanism was investigated. The detection of Cu(II) in actual serum samples could be realized sensitively via this efficient DNAzyme-based method.
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Técnicas Biossensoriais , DNA Catalítico , Quadruplex G , DNA Catalítico/metabolismo , Hemina , Hidróxidos , Peroxidase , PeroxidasesRESUMO
In this work, the sensitive detection of hydrogen sulfide (H2S) was realized at low cost and high efficiency through the application of silver-gold core-shell nanoprism (Ag@Au-np) combined with headspace single-drop microextraction (HS-SDME). After SDME, smartphone nanocolorimetry (SNC), with the aid of a smartphone camera and color picker software, was used to detect and quantify the H2S. The method took advantage of the inhibition of the ultraviolet-visible (UV-vis) signal caused by H2S etching of the Ag@Au-np preadded to the SDME solvent to measure the H2S concentration. The coating of the gold layer not only ensured the high stability of the nanomaterial but also enhanced the selectivity toward H2S. The HS-SDME method was simple to process and required only a droplet of solvent for analysis to be realized. This HS-SDME-SCN approach exhibited a calibration graph linearity of between 0.1 and 100 µM and a limit of detection of 65 nM (relative standard deviations of N% ( n = 3) < 4.80). A comparison with UV-vis spectrophotometry was conducted. The practical applicability of HS-SDME-SNC was successfully demonstrated by determining H2S in genuine biosamples (egg and milk).
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Ovos/análise , Ouro/química , Sulfeto de Hidrogênio/análise , Sulfeto de Hidrogênio/isolamento & purificação , Nanopartículas Metálicas/química , Leite/química , Prata/química , Animais , Calorimetria/métodos , Microextração em Fase Sólida/métodosRESUMO
CODAS syndrome is a multi-system developmental disorder characterized by cerebral, ocular, dental, auricular, and skeletal anomalies. Using whole-exome and Sanger sequencing, we identified four LONP1 mutations inherited as homozygous or compound-heterozygous combinations among ten individuals with CODAS syndrome. The individuals come from three different ancestral backgrounds (Amish-Swiss from United States, n = 8; Mennonite-German from Canada, n = 1; mixed European from Canada, n = 1). LONP1 encodes Lon protease, a homohexameric enzyme that mediates protein quality control, respiratory-complex assembly, gene expression, and stress responses in mitochondria. All four pathogenic amino acid substitutions cluster within the AAA(+) domain at residues near the ATP-binding pocket. In biochemical assays, pathogenic Lon proteins show substrate-specific defects in ATP-dependent proteolysis. When expressed recombinantly in cells, all altered Lon proteins localize to mitochondria. The Old Order Amish Lon variant (LONP1 c.2161C>G[p.Arg721Gly]) homo-oligomerizes poorly in vitro. Lymphoblastoid cell lines generated from affected children have (1) swollen mitochondria with electron-dense inclusions and abnormal inner-membrane morphology; (2) aggregated MT-CO2, the mtDNA-encoded subunit II of cytochrome c oxidase; and (3) reduced spare respiratory capacity, leading to impaired mitochondrial proteostasis and function. CODAS syndrome is a distinct, autosomal-recessive, developmental disorder associated with dysfunction of the mitochondrial Lon protease.
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Proteases Dependentes de ATP/genética , Anormalidades Craniofaciais/genética , Anormalidades do Olho/genética , Transtornos do Crescimento/genética , Luxação Congênita de Quadril/genética , Proteínas Mitocondriais/genética , Osteocondrodisplasias/genética , Serina Proteases/genética , Anormalidades Dentárias/genética , Proteases Dependentes de ATP/metabolismo , Adolescente , Animais , Linhagem Celular Tumoral , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Exoma , Feminino , Frequência do Gene , Células HEK293 , Células HeLa , Homozigoto , Humanos , Lactente , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Mitocôndrias/enzimologia , Proteínas Mitocondriais/metabolismo , Mutação , Fenótipo , Estrutura Terciária de Proteína , Proteólise , Serina Proteases/metabolismoRESUMO
BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls. RESULTS: Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis. CONCLUSIONS: Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS.
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Encéfalo/diagnóstico por imagem , Síndrome de DiGeorge/diagnóstico por imagem , Síndrome de DiGeorge/psicologia , Imagem de Tensor de Difusão , Rede Nervosa/diagnóstico por imagem , Transtornos do Comportamento Social/diagnóstico por imagem , Transtornos do Comportamento Social/psicologia , Adolescente , Estudos Transversais , Síndrome de DiGeorge/epidemiologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos do Comportamento Social/epidemiologia , Adulto JovemRESUMO
In this report, the adsorption characteristics and conformation changes of model protein bovine serum albumin (BSA) adsorbed on nanographene oxide (NGO) are described. The adsorption isotherms obtained at pH 4.0, 4.7, 7.4 and 8.8 show that NGO has the highest affinity for BSA in the acid environment of pH 4.0, but the protein adsorption capacity decreases with the pH value increasing. The data imply that the spontaneously binding of BSA to the NGO surfaces is mainly due to the protein conformation and an electrostatic attraction mechanism. The fluorescence and synchronous fluorescence spectroscopic studies show that NGO quenches the fluorescence of BSA both statically and dynamically, and induces obvious perturbations on the conformation of BSA as well as the microenvironments around the Trp and Tyr residues. Moreover, analysis of the secondary structure of the proteins via Fourier transform infrared spectroscopy revealed that evident secondary structural changes may undergo upon adsorption. This study gives an insight into the interaction between NGO and proteins, which is critical in the design of optimal graphene nanosheets-protein conjugates.
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Grafite/química , Nanopartículas/química , Nanotecnologia/métodos , Óxidos/química , Soroalbumina Bovina/química , Adsorção , Animais , Bovinos , Concentração de Íons de Hidrogênio , Ligação Proteica , Conformação Proteica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Triptofano/química , Tirosina/químicaRESUMO
The gender paradox in suicide research refers to the phenomenon that while males report higher suicide mortality, females suffer more from suicidal thoughts, leading to higher suicidal risks. This paradox may lead to the misconception that female suicides do not require as much attention. Therefore, there is an urgent need for researchers to shift their perspectives from the current male-centric approach to more inclusive knowledge for female suicidality. Following this, the current commentary emphasizes the importance of identifying and addressing the crucial but overlooked psychosocial factors underlying female suicidality. In addition, the ecological framework is employed as a guiding tool for exploring the intricate interplay of biological, psychological, societal, and cultural factors that are associated with female suicidality, thereby allowing researchers and stakeholders to develop more effective prevention and intervention strategies tailored to women's needs. Overall, this commentary calls for more refined and equitable approaches to suicide prevention that address the needs of individuals for all gender identities.
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Prevenção do Suicídio , Suicídio , Humanos , Feminino , Suicídio/psicologia , Masculino , Ideação Suicida , Fatores Sexuais , Fatores de RiscoRESUMO
Glioblastoma (GBM) is one of the deadliest primary brain tumors, but its diagnosis and curative therapy still remain a big challenge. Herein, neutrophil-targeting semiconducting polymer nanotheranostics (SSPNiNO) is reported for second near-infrared (NIR-II) fluorescence imaging-guided trimodal therapy of orthotopic glioblastoma in mouse models. The SSPNiNO are formed based on two semiconducting polymers acting as NIR-II fluorescence probe as well as photothermal conversion agent, respectively. A thermal-responsive nitric oxide (NO) donor and an adenosine 2A receptor (A2AR) inhibitor are co-integrated into SSPNiNO to enable trimodal therapeutic actions. SSPNiNO are surface attached with a neutrophil-targeting ligand to mediate their effective delivery into orthotopic GBM sites via a "Trojan Horse" manner, enabling high-sensitive NIR-II fluorescence imaging. Upon NIR-II light illumination, SSPNiNO effectively generates heat via NIR-II photothermal effect, which not only kills tumor cells and induces immunogenic cell death (ICD), but also triggers controlled NO release to strengthen tumor ICD. Additionally, the encapsulated A2AR inhibitor can modulate immunosuppressive tumor microenvironment by blocking adenosine-A2AR pathway, which further boosts the antitumor immunological effect to observably suppress the orthotopic GBM progression. This study can provide a multifunctional theranostic nanoplatform with cumulative therapeutic actions for NIR-II fluorescence imaging-guided effective GBM treatment.
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BACKGROUND: The aging of skeletal muscle is the leading cause of physical disability in older adults, currently effective treatment methods are lacking. Ginsenoside Rh4, an active component extracted from ginseng, possesses beneficial anti-inflammatory and anti-oxidative effects. PURPOSE: The aim of this study was to elucidate the antioxidant effect of ginsenoside Rh4 on aging skeletal muscle and its molecular mechanism of anti-aging of skeletal muscle. STUDY DESIGN: In this study, we employed a D-galactose-induced model of skeletal muscle aging to investigate whether ginsenoside Rh4 can delay the process of skeletal muscle senescence. METHODS: The effects of ginsenoside Rh4 on oxidative damage and inflammation in aging skeletal muscle were analyzed using immunofluorescence, immunohistochemistry, ELISA kits, H&E staining, flow cytometry, and protein immunoblotting. The changes of ginsenoside Rh4 on mitochondrial morphology were observed by transmission electron microscopy, and ELISA kits and protein immunoblotting analyzed the effects of ginsenoside Rh4 on mitochondrial homeostasis in skeletal muscle cells. The influence of ginsenoside Rh4 on the SIRT1 signaling pathway in aging skeletal muscle were investigated by protein immunoblotting, immunofluorescence, and ß-galactosidase staining. RESULTS: Our results showed that Rh4 improved the morphology of muscle fibers and produced an anti-inflammatory response. Furthermore, in vitro experiments indicated that ginsenosides reduced the production of senescent cells, while Rh4 effectively alleviated oxidative damage in skeletal muscle and restored mitochondrial balance. Transcriptome analysis and molecular docking showed that Rh4 improved mitochondrial homeostasis and delayed skeletal muscle aging by regulating the PGC-1α-TFAM and HIF-1α-c-Myc pathways via targeting SIRT1. CONCLUSION: Ginsenoside Rh4 improves oxidative stress and inflammation in skeletal muscle by activating SIRT1, deacetylating Nrf2, regulating PGC-1α-TFAM and HIF-1α-c-Myc pathways, and enhancing mitochondrial homeostasis, thus achieving the effect of delaying skeletal muscle aging.
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Ginsenosídeos , Ginsenosídeos/farmacologia , Sirtuína 1 , Simulação de Acoplamento Molecular , Músculo EsqueléticoRESUMO
Radiotherapy is a common cancer treatment approach in clinical practice, yet its efficacy has been restricted by tumor hypoxia. Nanomaterials-mediated systemic delivery of glucose oxidase (GOx) and catalase (CAT) or CAT-like nanoenzymes holds the potential to enhance tumor oxygenation. However, they face the challenge of intermediate (hydrogen peroxide [H2 O2 ]) escape during systemic circulation if the enzyme pair is not closely placed to largely decompose H2 O2 , leading to oxidative stress on normal tissues. In the present study, a oxygen-generating nanocascade, n(GOx-CAT)C7A , constructed by strategically placing an enzymatic cascade (GOx and CAT) within a polymeric coating rich in hexamethyleneimine (C7A) moieties, is reported. During blood circulation, C7A remains predominantly non-protonated , achieving prolonged blood circulation due to its low-fouling surface. Once n(GOx-CAT)C7A reaches the tumor site, the acidic tumor microenvironment (TME) induces protonation of C7A moieties, resulting in a positively charged surface for enhanced tumor transcytosis. Moreover, GOx and CAT are covalently conjugated into close spatial proximity (<10 nm) for effective H2 O2 elimination. As demonstrated by the in vivo results, n(GOx-CAT)C7A achieves effective tumor retention and oxygenation, potent radiosensitization and antitumor effects. Such a dual-enzyme nanocascade for smart O2 delivery holds great potential for enhancing the hypoxia-compromised cancer therapies.
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Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias/patologia , Peróxido de Hidrogênio , Estresse Oxidativo , Hipóxia Tumoral , Oxigênio , Glucose Oxidase/metabolismo , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Glutathione, referred to as GSH, abnormal physiologic level of GSH is an indication to some neurodegenerative diseases and cancers. A measurement of cellular GSH calls for rapid, sensitive, and selective methods. In this work, we rationally design and prepare Au@MnO2 core-shell composite nanoparticles combining with tetramethylbenzidine (TMB) molecules to determine intracellular GSH by Surface enhanced Raman scattering (SERS) technique. MnO2 plays multifunctional roles in the method, including the participation in catalyzing TMB to molecules form dimer charge-transfer complex (CTC) which own a great SERS signal reporter. With the addition of GSH, the MnO2 will be dissolving detaching CTC molecules from the surface of Au@MnO2 and resulting in a signal-oï¬ off SERS response and indirect and sensitive detection of GSH could be realized. The limit of detection of GSH by SERS method is as low as 0.1⯵mol/L and a good linear relationship of GSH is found in the range from 0.5 to 30⯵mol/L. Au@MnO2-SERS assay is successfully applied to detect cellular GSH, which is validated by using Enzyme-linked-immunoassay-based Kit. The Au@MnO2-SERS protocol has promising potential for clinical application.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Glutationa , Ouro , Compostos de Manganês , Óxidos , Análise Espectral Raman/métodosRESUMO
A highly sensitive triple-amplification assay for the detection of microRNA (miRNA) let-7a is reported in this work. The assay relies on the formation of magnetic two-dimensional DNA/Fe3O4 nanosheet networks initiated by the target miRNA-associated hybridization chain reaction. The Fe3O4 nanosheets in the DNA/Fe3O4 networks display peroxidase-like catalytic activity towards a colorimetric reaction, thereby producing a highly sensitive signal for the quantification of let-7a. Under optimal conditions, the assay achieved a detection limit of 13 aM at a signal-to-noise ratio of 3 and a linear calibration plot between 0.05 fM and 12 nM. Successful attempts were made in the quantification of let-7a in serum samples.
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Materiais Biomiméticos/química , DNA/química , Óxido Ferroso-Férrico/química , MicroRNAs/sangue , Humanos , Limite de Detecção , Fenômenos Magnéticos , Nanoestruturas/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Peroxidase/químicaRESUMO
OBJECTIVE: Detecting brain abnormalities in clinical high-risk populations before the onset of psychosis is important for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders. Co-occurring cellular and extracellular white matter alterations have previously been implicated after a first psychotic episode. The authors investigated whether or not cellular and extracellular alterations are already present in a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms. METHODS: Fifty individuals at clinical high risk, of whom 40 were never medicated, were compared with 50 healthy control subjects, group-matched for age, gender, and parental socioeconomic status. 3-T multishell diffusion MRI data were obtained to estimate free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW). RESULTS: Significantly lower FAT was observed in the clinical high-risk group compared with the healthy control group, but no statistically significant FW alterations were observed between groups. Lower FAT in the clinical high-risk group was significantly associated with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months. CONCLUSIONS: Cellular but not extracellular alterations characterized the clinical high-risk group, especially in those who experienced a decline in functioning. These cellular changes suggest an early deficit that possibly reflects a predisposition to develop attenuated psychotic symptoms. In contrast, extracellular alterations were not observed in this clinical high-risk sample, suggesting that previously reported extracellular abnormalities may reflect an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.
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Encéfalo/diagnóstico por imagem , Transtornos Psicóticos/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Imagem de Difusão por Ressonância Magnética , Espaço Extracelular/metabolismo , Feminino , Humanos , Masculino , Neuroimagem , Transtornos Psicóticos/patologia , Fatores de Risco , Água , Substância Branca/patologia , Adulto JovemRESUMO
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1) white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2) the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF), and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.
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Síndrome de DiGeorge/diagnóstico por imagem , Fibras Nervosas Mielinizadas/patologia , Adulto , Síndrome de DiGeorge/genética , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Aprendizado de Máquina , Masculino , Rede Nervosa/patologia , Testes Neuropsicológicos , Substância Branca/patologia , Adulto JovemRESUMO
OBJECTIVES: Stimulative nanostructures play a crucial role in developing the smart nanomedicine for high therapeutic efficacy with minimum adverse effects. Herein, a near-infrared (NIR) light-responsive nanohybrids p-nanographene oxide (GO)-copper sulfide (CuS)/indocyanine green (ICG) comprised of GO, CuS nanoparticles and photosensitizer ICG was fabricated to couple the photothermal property of CuS and photodynamic effect of ICG in one system in order to achieve the synergistic phototherapy. METHODS: pGO-CuS/ICG was constructed by self-assembling ICG on pGO-CuS nanostructure. Its physicochemical, photothermal and photodynamic properties were studied by spectroscopic methods. The in vitro cellular uptake, cytotoxicity, the single/combined photothermal therapeutic (PTT) and photodynamic therapeutic (PDT) effects were investigated with biological techniques. RESULTS: pGO-CuS/ICG exhibited high efficacy of photothermal conversation and singlet oxygen generation under NIR laser excitation. It entered into the target cancer cells probably via passive transmembrane pathway and exerted obvious PTT and PDT effect against the tumor cells upon irradiation with the respective 940 and 808 nm lasers. In particular, the tremendous synergistic efficacy of PDT and PTT had been demonstrated by tuning the NIR laser combined irradiation. CONCLUSIONS: This study promises the future applications of pGO-CuS/ICG as a NIR light activable theranostic nanodrug for deep-seated cancer noninvasive phototherapy.
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Cobre/administração & dosagem , Grafite/administração & dosagem , Nanopartículas/química , Fármacos Fotossensibilizantes/administração & dosagem , Fototerapia/métodos , Polietilenoglicóis/química , Humanos , NeoplasiasRESUMO
Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure.
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Corpo Caloso/lesões , Corpo Caloso/patologia , Futebol Americano/lesões , Substância Branca/lesões , Substância Branca/patologia , Adolescente , Adulto , Idade de Início , Idoso , Anisotropia , Criança , Pré-Escolar , Imagem de Tensor de Difusão , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Multimodal therapeutic agents based on nanomaterials for cancer combination therapy have attracted increasing attention. In this report, a novel photo- and chemoactive nanohybrid was fabricated by assembling photosensitizer Zn(II)-phthalocyanine (ZnPc) and anticancer drug doxorubicin (DOX) on the biocompatible poly-l-lysine (PLL)-grafted graphene (G-PLL). This nanocomplex of G-PLL/DOX/ZnPc showed excellent physiochemical properties, including high solubility and stability in biological solutions, high drug loading efficiency, pH-triggered drug release, and ability to generalize (1)O2 under light excitation. Compared to free drug molecules, cells treated with G-PLL/DOX/ZnPc showed a higher cellular uptake. In particular, G-PLL/DOX/ZnPc elicited a remarkable synergistic anticancer activity owing to combined photodynamic and chemotherapeutic effects. The combination dose reduction indexes revealed that combining DOX with ZnPc provided strong synergistic effects (combination index < 0.1) against three cancer cell lines tested (HeLa, MCF-7, and B16). Thus, this study demonstrates programmable dual-modality therapy exemplified by G-PLL/DOX/ZnPc to synergistically treat cancers.