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1.
J Nanobiotechnology ; 22(1): 240, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735931

RESUMO

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.


Assuntos
Ouro , Grafite , Estresse Oxidativo , Pontos Quânticos , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas , Óxido de Zinco , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Ouro/química , Grafite/química , Óxido de Zinco/química , Animais , Pontos Quânticos/química , Camundongos , Nanopartículas Metálicas/química , Apoptose/efeitos dos fármacos , Ácido Hialurônico/química , Elétrons
2.
Neuroimage ; 291: 120592, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548037

RESUMO

The growing trend of bilingual education between Chinese and English has contributed to a rise in the number of early bilingual children, who were exposed to L2 prior to formal language instruction of L1. The L2-L1 transfer effect in an L1-dominant environment has been well established. However, the threshold of L2 proficiency at which such transfer manifests remains unclear. This study investigated the behavioral and neural processes involved when manipulating phonemes in an auditory phonological task to uncover the transfer effect in young bilingual children. Sixty-two first graders from elementary schools in Taiwan were recruited in this study (29 Chinese monolinguals, 33 Chinese-English bilinguals). The brain activity was measured using fNIRS (functional near-infrared spectroscopy). Bilingual children showed right lateralization to process Chinese and left lateralization to process English, which supports more on the accommodation effect within the framework of the assimilation-accommodation hypothesis. Also, compared to monolinguals, bilingual children showed more bilateral frontal activation in Chinese, potentially reflecting a mixed influence from L2-L1 transfer effects and increased cognitive load of bilingual exposure. These results elucidate the developmental adjustments in the neural substrates associated with early bilingual exposure in phonological processing, offering valuable insights into the bilingual learning process.


Assuntos
Multilinguismo , Criança , Humanos , Linguística , China
3.
Eye Contact Lens ; 49(12): 512-520, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37728877

RESUMO

OBJECTIVE: To investigate the changes in choroidal thickness and axial length after orthokeratology in adolescents with low-to-moderate myopia and to explore the relationship between choroidal thickness and axial length variation. METHODS: Thirty eyes with low-to-moderate myopia were retrospectively studied, and optometric data were collected before and after 6 months of continuous orthokeratology. Axial length and choroidal and foveal thicknesses were measured using optical biometry and enhanced depth imaging-spectral domain optical coherence tomography, respectively. RESULTS: Axial length in the low myopia group increased ( P <0.001) after 6 months of orthokeratology, and the variation was greater than that in the moderate myopia group ( P <0.05). The subfoveal choroidal thickness in low and moderate myopia groups increased ( P <0.01), and the variation was greater in the moderate myopia group ( P <0.05). Choroidal thickness in all seven measured spots increased, with the variation of subfovea, nasal 1 mm to fovea, and temporal 1 mm to fovea being statistically significant ( P <0.001, P <0.05, and P <0.05). The change in axial length was negatively associated with subfoveal and average choroidal thicknesses ( P <0.01). CONCLUSION: Adolescents with moderate myopia presented better axial length control after 6 months of orthokeratology. The choroidal thickness of low and moderate myopic eyes increased, and the variation was more significant in moderate myopic eyes. The axial length control effects can be associated with an increase in the subfoveal and average choroidal thickness.


Assuntos
Comprimento Axial do Olho , Miopia , Humanos , Adolescente , Estudos Retrospectivos , Miopia/terapia , Refração Ocular , Acuidade Visual , Corioide , Tomografia de Coerência Óptica/métodos
4.
J Ocul Pharmacol Ther ; 39(9): 643-652, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37582278

RESUMO

Purpose: To investigate the efficacy and safety of scleral cross-linking (CXL) using Genipin in the treatment of juvenile guinea pigs with high myopia. Methods: Twenty-four 4-week-old tricolor guinea pigs with high myopia of diopter ≤ -6.0 DS in the right eye were randomly divided into two groups: Genipin CXL group and control group (n = 12 for each group). They received separately form-deprivation (FD) combined with sub-tenon injection, and the former was 0.5% Genipin solution, while the latter was 0.9% saline solution. Refractive error, axial length (AL), intraocular pressure (IOP), and structural and vasculature optic disc changes in optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed at baseline and at 3 weeks after injection. Results: Baseline parameters were similar between the two groups (P > 0.05). After 3 weeks of the intervention, the difference of AL between the two groups was statistically significant (t = -11.28, P < 0.001). Besides, IOP increased in both groups, and the changes of IOP between the two groups were statistically significant (t = 2.80, P = 0.01). The average cup-disc ratio (C/D) (t = 3.11, P = 0.006) and the vertical C/D (t = 2.96, P = 0.009) of OCT-related optic disc parameters in the Genipin CXL group increased, and the differences were statistically significant compared with the control group. Conclusion: The CXL method of sub-tenon injection of Genipin solution could effectively inhibit the progression of myopia in juvenile guinea pigs with highly myopic eyes combined with FD. The slightly elevated IOP and increased C/D of some fundus optic discs should be further assessed.


Assuntos
Miopia , Cobaias , Animais , Miopia/tratamento farmacológico , Esclera , Iridoides/farmacologia , Iridoides/uso terapêutico , Pressão Intraocular
5.
J Orthop Surg Res ; 18(1): 416, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291606

RESUMO

BACKGROUND: The goat cervical spine represents a promising alternative for human specimen in spinal implant testing, but the range of motion (ROM) of the spine is lacking. We aimed to evaluate and compare the ROMs of fresh goat and human mid-cervical spine specimens. METHODS: Ten fresh adult healthy male goat cervical spine specimens (G group) and ten fresh frozen adult healthy human cervical spine specimens (average age: 49.5 ± 12.1 years; 6 males, 4 females) (H group) were included. The ROMs of each specimen were biomechanically tested at the C2-3, C3-4, C4-5 and C2-5 levels at 1.5 Nm and 2.5 Nm torque and recorded. The ROMs of different levels of goat cervical samples were compared to those of human cervical samples using an independent sample t test. Significance was defined as a P value of less than 0.05. RESULTS: At the C2-3, C3-4 and C4-5 levels, the ROMs of the goat cervical spine were significantly larger than those of the human cervical spine in all directions except extension under 1.5 Nm torque; under 2.5 Nm torque, the ROMs of the goat cervical spine at the C2-3 and C3-4 levels were significantly larger than those of humans in the pure movement of flexion, lateral bending and axial rotation, and the ROMs for axial rotation of the goat specimens and human specimens were comparable. Under both 1.5 Nm and 2.5 Nm torque, the goat cervical spine displayed a much greater ROM in all directions at the C2-5 level. CONCLUSIONS: Several segmental ROMs of fresh goat and human cervical spine specimens were recorded in this investigation. We recommend using goat cervical specimens as an alternative to fresh human cervical specimens in future studies when focusing only on the ROMs of C2-3, C3-4 and C4-5 in flexion under a torque of 1.5 Nm or the ROMs of C2-3 and C3-4 in flexion and rotation under a torque of 2.5 Nm.


Assuntos
Cabras , Fusão Vertebral , Adulto , Feminino , Animais , Humanos , Masculino , Pessoa de Meia-Idade , Vértebras Cervicais , Pescoço , Amplitude de Movimento Articular , Fenômenos Biomecânicos
6.
J Orthop Translat ; 37: 61-68, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36225948

RESUMO

Objective: Anterior cervical corpectomy and fusion (ACCF) has been widely used in the treatment of cervical spondylotic myelopathy (CSM) but is accompanied by unavoidable motion loss and destruction of vertebra. We aim to evaluate the range of motion (ROM) of caprine cervical spine constructs implanted with cervical artificial disc and vertebra system (ADVS). The purpose of this study was to investigate the biomechanical properties of the ADVS from an in vivo caprine cervical spine non-fusion model. Methods: Twelve goats were randomly divided into ADVS or control group, with 6 animals in each group. The animals in the ADVS group were implanted with ADVS at the C4 level. The cervical spine constructs were harvested 6 months after the operation. The ROM of cervical spine specimens in the ADVS group was recorded. Biomechanical testing of the specimens in the control group were conducted to evaluate the ROM of the cervical spine specimens under intact and fixed condition (C3-C5) by an anterior plate, respectively. Results: The biomechanical outcomes showed that the ROM of the levels (C3-C5) implanted with ADVS was maintained. The ROM in the adjacent level (C2-3) did not increase significantly comparing with intact group. Conclusions: In general, ADVS could preserve the ROM of operative levels and could reconstruct the height of the vertebra. ADVS did not increase the ROM of upper adjacent level. This device provides a non-fusion method for the treatment of patients suffering from CSM. However, improvements on the design of ADVS are still needed. Translational potential statement: This study introduced a novel cervical spinal implant, which was designed to have the ability of motion preservation and vertebra construction. Our study provided a non-fusion procedure in the treatment of CSM after ACCF.

7.
PLoS One ; 17(7): e0271030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35793352

RESUMO

Demoralization has become increasingly prevalent among college students who have lost motivation in life and feel hopeless about their future. Many college students who demonstrate symptoms of demoralization are neglected because they might fail to typical symptoms of depression. Taiwanese college students are simultaneously influenced by bicultural-self system, such as individual- and social-oriented views of self, which vary considerably in the view of self, achievement motivation, and the value of self-realization, and may even create contradictory expectations and behavioral standard. The purpose of this study was to investigate the extent of the relationship between attitude towards demoralization, individual- and social-oriented views of self. Three-hundred fifty-six college students completed the online questionnaire, which was designed to explore their demoralization status and cultural differences. Four groups were divided into bicultural self, individual-oriented self, social-oriented self, and unintegrated self. Bicultural group demonstrated significantly lower demoralization overall scores than other groups. Moreover, the five dimensions of demoralization in college students were mostly significantly and negatively correlated with individual- and social-oriented views of self, indicating that college students' bicultural views of self may contribute to or prevent demoralization.


Assuntos
Desmoralização , Afeto , Humanos , Motivação , Autoimagem , Estudantes
8.
Gene ; 804: 145902, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34403773

RESUMO

BACKGROUNDS: Osteonecrosis of the femoral head (ONFH) is one of the common and complicated diseases in the orthopedic clinic. Previous studies indicate that genetic factors play a crucial role in the occurrence of ONFH. This case-control study aimed to investigate the associations of MIR137HG genetic polymorphisms with the alcohol-induced ONFH risk. METHODS: A total of 731 participants were recruited to detect the effect of MIR137HG SNPs on the alcohol-induced ONFH risk in a Chinese male population. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations. Multifactor dimensionality reduction (MDR) was used to analyze the SNP-SNP interaction with the alcohol-induced ONFH risk. RESULTS: Our study showed that rs7549905 played a protective role in alcohol-induced ONFH risk (OR 0.57, p = 0.045). Stratified analysis indicated that rs9440302 was associated with an increased risk of patients aged >45 years (OR 2.00, p = 0.038), and rs7549905 showed a reduced risk in patients aged ≤ 45 years (OR 0.43, p = 0.023). In addition, we found that rs9440302 and rs7554283 exhibited a significantly increased susceptibility of III-IV grade alcohol-induced ONFH patients (OR 2.34, p = 0.003; OR 2.13, p = 0.011, respectively). We also observed that rs12138817 was related to an increased risk in patients with >21 months of course (OR 1.77, p = 0.043). Interestingly, rs17371457 showed a significant correlation with low-density lipoprotein-cholesterol (p = 0.040). CONCLUSION: Our study suggests that MIR137HG genetic variants are associated with the alcohol-induced ONFH susceptibility in a Chinese male population, which may give scientific evidence for exploring molecular mechanisms of the alcohol-induced ONFH.


Assuntos
Necrose da Cabeça do Fêmur/genética , MicroRNAs/genética , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Induzidos por Álcool/epidemiologia , Transtornos Induzidos por Álcool/genética , Transtornos Induzidos por Álcool/metabolismo , Povo Asiático/genética , Estudos de Casos e Controles , Criança , China/epidemiologia , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/epidemiologia , Necrose da Cabeça do Fêmur/patologia , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único
9.
Hum Exp Toxicol ; 40(10): 1612-1623, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33779331

RESUMO

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1ß and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.


Assuntos
Apoptose/fisiologia , Células da Medula Óssea/fisiologia , Exossomos/metabolismo , Inflamação/metabolismo , Células-Tronco Mesenquimais/fisiologia , Traumatismos da Medula Espinal/metabolismo , Animais , Humanos , Masculino , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Células PC12 , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
10.
Medicine (Baltimore) ; 100(8): e24255, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663046

RESUMO

BACKGROUND: The prognostic role of the expression of metastasis-associated in colon cancer-1 (MACC1) in gynecologic cancers and breast cancer remains unclear. The aim of this systematic review and meta-analysis was to determine the prognostic significance of MACC1 expression in gynecologic cancers and breast cancer. MATERIALS AND METHODS: PubMed, Web of Science and Embase were comprehensively searched up to February 9, 2020. Studies focusing on the relationship between the expression of MACC1 and prognosis in gynecologic cancers and breast cancer were included into the analysis. Pooled hazard ratio (HR) or odd ratio with 95% confidence interval (CI) was used to estimate the prognostic value of the expression of MACC1. RESULTS: A total of 1,811patients with gynecologic cancers or breast cancer were included into the analysis. Patients with high expression of MACC1 tended to suffer a shorter overall survival (HR = 2.76, 95%CI = 2.12-3.59, P < .01) and recurrence-free survival (HR = 2.37, 95%CI = 1.44-3.90, P < .01) compared to those with low expression of MACC1. High expression of MACC1 was significantly associated with worse tumor differentiation (P = .04), more advanced FIGO stage (P < .01) and earlier lymph node metastasis (P < .01) compared to low expression of MACC1. CONCLUSION: Compared to low expression of MACC1, high expression of MACC1 predicts a worse prognosis of gynecologic cancers and breast cancer. The expression of MACC1 can serve as a prognostic indicator of gynecologic cancers and breast cancer.


Assuntos
Neoplasias da Mama/patologia , Neoplasias dos Genitais Femininos/patologia , Transativadores/biossíntese , Feminino , Humanos , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Projetos de Pesquisa , Análise de Sobrevida , Metanálise como Assunto
11.
J Child Psychol Psychiatry ; 62(9): 1090-1099, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33543509

RESUMO

BACKGROUND: Youths with autism spectrum disorder (ASD) rely more on lower-level visual processing as revealed by greater occipital activation, yet less effectively engage higher-level processing of modality-independent semantic knowledge as indicated by reduced frontal activation, compared to typically developing (TD) youths. However, little is known about age-dependent differences in neural connectivity during semantic processing in youths with ASD as compared to TD youths. METHODS: Four groups were recruited: 31 ASD children (mean age = 10.5 years old), 33 TD children (mean age = 10.4), 30 ASD adolescents (mean age = 14.9), and 34 TD adolescents (mean age = 15.1). We explored their differences in neural connectivity by using functional magnetic resonance imaging (fMRI) with psychophysiological interaction (PPI) during semantic judgments. RESULTS: In comparison with TD children, children with ASD showed greater activation in the left cuneus and weaker connectivity between the left cuneus and left middle temporal gyrus (MTG). In comparison with TD adolescents, adolescents with ASD showed less activation in the left inferior frontal gyrus (IFG) and weaker functional connectivity between the left IFG and left MTG. CONCLUSIONS: Children with ASD may rely more on visual processes in the occipital cortex that are disconnected from modality-independent semantics in the temporal cortex. However, adolescents with ASD may less effectively engage frontal mechanisms involved in the top-down control of modality-independent semantic knowledge in the temporal cortex. Our findings provide evidence of developmental differences in the neural substrates of the alterations in semantic processing in youths with ASD compared to TD youths.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Adolescente , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Criança , Humanos , Imageamento por Ressonância Magnética , Vias Neurais , Semântica
12.
Front Hum Neurosci ; 14: 233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714169

RESUMO

Previous studies have investigated the developmental differences of semantic processing regarding brain activation between adults and children. However, little is known about whether the patterns of structural connectivity and effective connectivity differ between adults and children during semantic processing. Functional magnetic resonance imaging (fMRI), diffusion spectrum imaging (DSI), and dynamic causal modeling (DCM) were used to study the developmental differences of brain activation, structural connectivity, and effective connectivity during semantic judgments. Twenty-six children (8- to 12-year-olds) and 26 adults were asked to indicate if character pairs were related in meaning. Compared to children, adults showed greater activation in the left ventral inferior frontal gyrus (IFG) and left middle temporal gyrus (MTG). Also, adults had significantly greater structural connectivity in the left ventral pathway (inferior frontal occipital fasciculus, IFOF) than children. Moreover, adults showed significantly stronger bottom-up effects from left fusiform gyrus (FG) to ventral IFG than children in the related condition. In conclusion, our findings suggest that age-related increases in brain activation (ventral IFG and MTG), IFOF, and effective connectivity (from FG to ventral IFG) might be associated with the bottom-up influence of orthographic representations on retrieving semantic representations for processing Chinese characters.

13.
J Ocul Pharmacol Ther ; 36(2): 97-101, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31800355

RESUMO

Purpose: To investigate the efficacy and safety of topical low-concentration (0.01%) atropine for controlling near work-induced transient myopia (NITM) in a young Chinese population. Methods: This was a randomized, double-blinded, placebo-controlled study. The participants were randomly divided into the 0.5% hydroxypropyl-methylcellulose-treated group (control group) or 0.01% atropine-treated group (study group). Participants' pulse rate, respiration rate, intraocular pressure, pupil diameter, and magnitude of initial NITM were evaluated at baseline and on day 7 and 14 during treatment. In addition, ocular discomfort and adverse effects were recorded. Results: Of the initial 176 participants, 145 (82.4%) completed the 14-day treatment and all evaluations. At baseline, no difference in the magnitude of initial NITM was observed between the control and study groups (P = 0.826). However, the magnitude of initial NITM of the study group was significantly lower at both day 7 (-0.11 ± 0.227 D) and day 14 (0.076 ± 0.183 D) after treatment initiation, compared with the magnitude of initial NITM in the control group (P < 0.001). No serious complications were observed. However, significantly larger pupil diameters were noted on day 7 and 14 in the study group than in the control group (P < 0.001). Conclusions: We speculate that daily topical 0.01% atropine application effectively reduced the magnitude of initial NITM, without any serious complications. The minimal pupil dilation induced by the treatment was acceptable. Low-concentration atropine may be useful in clinical settings as treatment for young patients with NITM.


Assuntos
Atropina/uso terapêutico , Miopia/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Leitura , Administração Tópica , Adolescente , Povo Asiático , Atropina/administração & dosagem , Criança , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Miopia/fisiopatologia , Soluções Oftálmicas/administração & dosagem , Testes Visuais
14.
Nat Med ; 25(4): 597-602, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833747

RESUMO

Spitzoid melanoma is a specific morphologic variant of melanoma that most commonly affects children and adolescents, and ranges on the spectrum of malignancy from low grade to overtly malignant. These tumors are generally driven by fusions of ALK, RET, NTRK1/3, MET, ROS1 and BRAF1,2. However, in approximately 50% of cases no genetic driver has been established2. Clinical whole-genome and transcriptome sequencing (RNA-Seq) of a spitzoid tumor from an adolescent revealed a novel gene fusion of MAP3K8, encoding a serine-threonine kinase that activates MEK3,4. The patient, who had exhausted all other therapeutic options, was treated with a MEK inhibitor and underwent a transient clinical response. We subsequently analyzed spitzoid tumors from 49 patients by RNA-Seq and found in-frame fusions or C-terminal truncations of MAP3K8 in 33% of cases. The fusion transcripts and truncated genes all contained MAP3K8 exons 1-8 but lacked the autoinhibitory final exon. Data mining of RNA-Seq from the Cancer Genome Atlas (TCGA) uncovered analogous MAP3K8 rearrangements in 1.5% of adult melanomas. Thus, MAP3K8 rearrangements-uncovered by comprehensive clinical sequencing of a single case-are the most common genetic event in spitzoid melanoma, are present in adult melanomas and could be amenable to MEK inhibition.


Assuntos
Genoma Humano , MAP Quinase Quinase Quinases/genética , Melanoma/genética , Proteínas Proto-Oncogênicas/genética , Análise de Sequência de DNA , Animais , Criança , Éxons/genética , Humanos , Masculino , Camundongos , Mutação/genética , Células NIH 3T3 , Proteínas de Fusão Oncogênica/genética
15.
Brain Lang ; 189: 10-19, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30593860

RESUMO

Semantic knowledge has thematic relations of contiguity based on association and taxonomic relations of similarity based on shared features to form categories. It is unknown if there are distinct brain networks between thematic and taxonomic organizations in children and if this distinction is related to changes in specialized brain regions with age and/or skill. We orthogonally manipulated association strength (strong, weak) and categorical relatedness (high, low) to examine 10- to 14-year-old children over a two-year interval. Moreover, we examined whether initial behavioral performance predicted brain activation changes. Weak versus strong association strength produced greater activation over time in left middle temporal gyrus and inferior frontal gyrus, and initial accuracy predicted activation changes in the latter. Moreover, high versus low categorical relatedness produced greater activation over time in left occipito-temporal cortex and precuneus, and initial accuracy predicted activation changes in the latter. These developmental findings suggest different organization for thematic and taxonomic relations.


Assuntos
Encéfalo/fisiologia , Desenvolvimento da Linguagem , Semântica , Percepção da Fala , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Mapeamento Encefálico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino
16.
Exp Ther Med ; 16(6): 5190-5200, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30546414

RESUMO

3'-Phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) has been shown to be important in the development of normal skeletal structure. The aim of the present study was to evaluate the role of PAPSS2 in the differentiation of chondrocytes as well as their mechanisms. Using RNA interference-mediated via a lentivirus and a retrovirus, PAPSS2 gene silence and overexpression in ATDC5 chondrogenic cells were performed. Chondrocyte differentiation and chondrogenic-related gene markers associated with extracellular matrix formation were noted. The mRNA and protein expression for Wnt4, ß-catenin and SOX9 genes were observed. The PAPSS2 transcript expression levels progressively decline in ATDC5-induced chondrocyte-like cells during differentiation. Silencing of PAPSS2 expression had a significantly attenuating effect on cell differentiation and decreased expression of collagen II and X. In contrast, over-expression of PAPSS2 promoted the differentiation of ATDC5 chondrogenic cells. The mRNA expression levels of Wnt4 and SOX9 decreased significantly in PAPSS2 knock down cells vs. control cells. However, this expression was increased in the cells over-expressing PAPSS2. These data indicate that PAPSS2 regulates aggrecan activity as well as cell differentiation. The findings favor a mechanism by which PAPSS2 induces differentiation in ATDC5 cells via direct regulation of early signaling events that promote formation of collagenous matrix components. This control is probably mediated via extracellular matrix formation Wnt/ß-catenin signaling pathways.

18.
RNA ; 24(8): 1056-1066, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29844105

RESUMO

The recent identification of compounds that interact with the spliceosome (sudemycins, spliceostatin A, and meayamycin) indicates that these molecules modulate aberrant splicing via SF3B1 inhibition. Through whole transcriptome sequencing, we have demonstrated that treatment of Rh18 cells with sudemycin leads to exon skipping as the predominant aberrant splicing event. This was also observed following reanalysis of published RNA-seq data sets derived from HeLa cells after spliceostatin A exposure. These results are in contrast to previous reports that indicate that intron retention was the major consequence of SF3B1 inhibition. Analysis of the exon junctions up-regulated by these small molecules indicated that these sequences were absent in annotated human genes, suggesting that aberrant splicing events yielded novel RNA transcripts. Interestingly, the length of preferred downstream exons was significantly longer than the skipped exons, although there was no difference between the lengths of introns flanking skipped exons. The reading frame of the aberrantly skipped exons maintained a ratio of 2:1:1, close to that of the cassette exons (3:1:1) present in naturally occurring isoforms, suggesting negative selection by the nonsense-mediated decay (NMD) machinery for out-of-frame transcripts. Accordingly, genes involved in NMD and RNAs encoding proteins involved in the splicing process were enriched in both data sets. Our findings, therefore, further elucidate the mechanisms by which SF3B1 inhibition modulates pre-mRNA splicing.


Assuntos
Compostos de Epóxi/farmacologia , Éxons/genética , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/genética , Biossíntese de Proteínas/genética , Fatores de Processamento de RNA/antagonistas & inibidores , Fatores de Processamento de RNA/genética , Splicing de RNA/genética , Compostos de Espiro/farmacologia , Spliceossomos/genética , Sequência de Bases , Linhagem Celular Tumoral , Células HCT116 , Células HeLa , Humanos , Degradação do RNAm Mediada por Códon sem Sentido/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Fases de Leitura/genética , Análise de Sequência de RNA , Transcriptoma/genética
19.
Hum Brain Mapp ; 39(10): 3827-3835, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29749060

RESUMO

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Endofenótipos , Função Executiva/fisiologia , Neuroimagem Funcional/métodos , Inibição Psicológica , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Percepção Visual/fisiologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Irmãos , Teste de Stroop
20.
Sensors (Basel) ; 18(1)2018 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-29301318

RESUMO

Advances in acoustic technology and instrumentation now make it possible to explore marine resources. As a significant component of ocean exploration, underwater acoustic target tracking has aroused wide attention both in military and civil fields. Due to the complexity of the marine environment, numerous techniques have been proposed to obtain better tracking performance. In this paper, we survey over 100 papers ranging from innovative papers to the state-of-the-art in this field to present underwater tracking technologies. Not only the related knowledge of acoustic tracking instrument and tracking progress is clarified in detail, but also a novel taxonomy method is proposed. In this paper, algorithms for underwater acoustic target tracking are classified based on the methods used as: (1) instrument-assisted methods; (2) mode-based methods; (3) tracking optimization methods. These algorithms are compared and analyzed in the aspect of dimensions, numbers, and maneuvering of the tracking target, which is different from other survey papers. Meanwhile, challenges, countermeasures, and lessons learned are illustrated in this paper.

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