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1.
Nanotechnology ; 31(3): 035305, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31569084

RESUMO

We present the plasmon-enhanced linear and second-order surface nonlinear optical response of silver nanoparticles (Ag NPs) fabricated using a femtosecond pulse. Theoretical analysis indicates Ag NPs with a diameter of ∼100 nm have excellent linear response within the visible band, and the electric field intensity enhancement factor reaches ∼105 under excitation of continuous light of 632.8 nm. Meanwhile, the simulation result of second-order surface nonlinear optical response shows that the second harmonic conversion efficiency of the Ag NPs dimer is two orders of magnitude higher than that of a single Ag NP, under excitation of a femtosecond pulse. In experiment, the linear response of Ag NPs is examined using surface-enhanced Raman spectroscopy (SERS) with a Raman enhancement factor of ∼1.7 × 1010, revealing the excellent linear optical response of Ag NPs. Moreover, the spectra of the second harmonic can be measured clearly under conditions of an average pump power of 40 µW, revealing the excellent second-order surface nonlinear optical response of Ag NPs.

2.
Nanotechnology ; 31(2): 025704, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31550686

RESUMO

Self-healing polymer materials (SHPM) have aroused great interests in recent years. Ideal SHPM should have not only simple operations, but also high elongations at break, tensile strain and self-healing properties at room temperature. Herein, the amidated carbon fibers (CFs) reinforced self-healing polymer composites were designed by hydrogen bonding interaction between functionalized CFs and hyperbranched polymers. The amidated CFs were prepared by transformation of hydroxyl to acylamino through a one-step amidation. By introducing amidated CFs, amidated CFs self-healing polymer composites (called AD-CF) exhibited many desirable characteristics compared to pure polymer composites, such as a better elasticity, lower healing temperatures, and higher self-healing efficiencies. The stress-strain test was selected to carefully study the self-healing property of the AD-CF. The observed same recovery condition, i.e. without any mechanical breakdown after the 10 sequential cycles of cutting and healing indicates no aging of the AD-CF. The ability of AD-CF to exhibit a soft state and rapid self-healing at room temperature makes it possible for much wider applications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31425724

RESUMO

BACKGROUND: Schizophrenia (SCZ) is a severe mental disorder. Both environmental and genetic factors contribute to the development of SCZ. The estimated heritability of SCZ is about 80%. Previous genetic studies of SCZ mainly focused on the genetic variations associated the risk of SCZ. Limited efforts are paid to explore the roles and biological mechanism of nuclear acid methylation implicated in the pathogenesis of SCZ. METHODS: A two-stage integrative analysis of SCZ GWAS and nuclear acid methylation functional annotation data (including meQTLs and m6A) was performed in this study. First, the discovery GWAS of SCZ was aligned with genomic meQTLs and m6A annotation data to identify the candidate genes associated with SCZ. Second, another independent replication GWAS dataset of SCZ was applied to validate the discovery results. Furthermore, the functional relevance of identified candidate genes with SCZ were validated by the mRNA expression profiling of SCZ brain tissues. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes was performed by the DAVID tool. RESULTS: The two-stage integrative analysis detected 106 meQTLs related candidate genes for SCZ. After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1. Besides, for meQTLs, 29 SCZ associated pathways and 56 SCZ associated GO terms were detected, such as cell adhesion molecules and asthma. For m6A, 25 candidate genes were detected by the two-stage integrative analysis for SCZ, such as ZSCAN12, HLA-DQA1 and SNX19. Furthermore, 17 of the 25 genes were detected in the mRNA expression profiling of SCZ brain tissues. CONCLUSION: This study identified multiple SCZ associated genes and pathways, supporting the implication of nuclear acid methylation in the pathogenesis of SCZ.

4.
Gene ; 723: 144142, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589957

RESUMO

DNA methylation is an epigenetic alteration that may lead to carcinogenesis by silencing key tumor suppressor genes. Hypermethylation of the paired box gene 1 (PAX1) promoter is important in cervical cancer development. Here, PAX1 methylation levels were compared between Uyghur and Han patients with cervical lesions. Data on PAX1 methylation in different cervical lesions were obtained from the Gene Expression Omnibus (GEO) database, whereas data on survival and PAX1 mRNA expression in invasive cervical cancer (ICC) were retrieved from the Cancer Genome Atlas (TCGA) database. MassARRAY spectrometry was used to detect methylation of 19 CpG sites in the promoter region of PAX1, whereas gene mass spectrograms were drawn by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Human papillomavirus (HPV) 16 infection was detected by polymerase chain reaction. PAX1 methylation in high-grade squamous intraepithelial lesion (HSIL) and ICC was significantly higher than in normal tissues. PAX1 hypermethylation was associated with poor prognosis and reduced transcription. ICC-specific PAX1 promoter methylation involved distinct CpG sites in Uyghur and Han patients HPV16 infection in HSIL and ICC patient was significantly higher than in normal women (p < 0.05). Our study revealed a strong association between PAX1 methylation and the development of cervical cancer. Moreover, hypermethylation of distinct CpG sites may induce HSIL transformation into ICC in both Uyghur and Han patients. Our results suggest the existence of ethnic differences in the genetic susceptibility to cervical cancer. Finally, PAX1 methylation and HPV infection exhibited synergistic effects on cervical carcinogenesis.


Assuntos
Carcinoma de Células Escamosas/virologia , Metilação de DNA , Papillomavirus Humano 16/patogenicidade , Fatores de Transcrição Box Pareados/genética , Infecções por Papillomavirus/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/virologia , Neoplasias do Colo do Útero/virologia , Carcinoma de Células Escamosas/genética , China/etnologia , DNA Viral/genética , Bases de Dados Factuais , Regulação para Baixo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16/genética , Humanos , Infecções por Papillomavirus/genética , Prognóstico , Regiões Promotoras Genéticas , Lesões Intraepiteliais Escamosas Cervicais/genética , Análise de Sobrevida , Neoplasias do Colo do Útero/genética
5.
Planta Med ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671467

RESUMO

Four new barringtogenol C-type triterpenoid saponins, namely acerplatanosides A - D (1: -4: ), along with 22 known compounds (5: -26: ), were isolated from the stem bark of Norway maple (Acer platanoides). Their structures were elucidated on the basis of comprehensive spectroscopic analyses and chemical hydrolysis. This is the first report of triterpenoid saponins isolated from Norway maple. Compounds 1, 3: , and 4: showed cytotoxicity against 4 human cancer cell lines with IC50 values ranging from 9.4 to 39.5 µM.

6.
Anal Bioanal Chem ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673753

RESUMO

A candidate reference measurement procedure (RMP) based on isotope dilution coupled with liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) was developed and validated for the quantification of 17α-hydroxyprogesterone (17-OHP) in human plasma. 17-OHP spiked with a deuterium-labeled internal standard was extracted from plasma by liquid-liquid extraction with 1 mL n-hexane/ethyl acetate (3:2, v/v). Reversed-phase chromatography and positive electrospray ionization were used in the ID-LC-MS/MS. Gradient elution coupled with use of a C18-packed ultrahigh-performance liquid chromatography column allowed complete baseline resolution of 17-OHP from its structural analogue desoxycorticosterone in 6 min. To determine the 17-OHP level in human plasma, a bracketing calibration method was used to give higher accuracy and precision. The limit of detection and the lower limit of the measuring interval for the candidate RMP were 2.1 pg/mL (6.4 pmol/L) and 4.6 pg/mL (13.9 pmol/L), respectively. Extraction recovery was determined to be (96.08 ± 3.03)% (n = 3). Imprecision (intra-assay and interassay) was 4.03% or less at 0.83, 15.19, 64.22, and 313.46 ng/mL (2.51, 45.97, 194.34, and 948.56 nmol/L, respectively). Recoveries ranged from 98.05% to 102.24%. When comparing our RMP results with those obtained with an established RMP via International Federation of Clinical Chemistry and Laboratory Medicine external quality assessment scheme for reference laboratories in laboratory medicine (RELA) samples, we found that the biases ranged from -1.99% to 3.08% against the targets. No interference was observed, and the linear response ranged from 0.47 to 958.63 ng/mL (1.42 to 2900.90 nmol/L). Moreover, the candidate RMP was used to measure the concentration of 17-OHP in human plasma and was compared with an immunoassay using 40 plasma samples. The performance of the method meets the needs of an RMP (total coefficient of variation of 5% or less and bias of 3.08% or less). This method can be used for reference material value assignment of 17-OHP in human plasma matrix. It could also serve as an accurate reference baseline for routine methods to increase the accuracy and precision of certain clinical laboratory measurements. Graphical abstract Selected ion chromatograms obtained by liquid chromatography-tandem mass spectrometry with a C18 column for 17α-hydroxyprogesterone (17-OHP) from a plasma sample.

7.
Eur Radiol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31673835

RESUMO

PURPOSE: To develop a radiomics-based model to stratify the risk of early progression (local/regional recurrence or metastasis) among patients with hypopharyngeal cancer undergoing chemoradiotherapy and modify their pretreatment plans. MATERIALS AND METHODS: We randomly assigned 113 patients into two cohorts: training (n = 80) and validation (n = 33). The radiomic significant features were selected in the training cohort using least absolute shrinkage and selection operator and Akaike information criterion methods, and they were used to build the radiomic model. The concordance index (C-index) was applied to evaluate the model's prognostic performance. A Kaplan-Meier analysis and the log-rank test were used to assess risk stratification ability of models in predicting progression. A nomogram was plotted to predict individual risk of progression. RESULTS: Composed of four significant features, the radiomic model showed good performance in stratifying patients into high- and low-risk groups of progression in both the training and validation cohorts (log-rank test, p = 0.00016, p = 0.0063, respectively). Peripheral invasion and metastasis were selected as significant clinical variables. The combined radiomic-clinical model showed good discriminative performance, with C-indices 0.804 (95% confidence interval (CI), 0.688-0.920) and 0.756 (95% CI, 0.605-0.907) in the training and validation cohorts, respectively. The median progression-free survival (PFS) in the high-risk group was significantly shorter than that in the low-risk group in the training (median PFS, 9.5 m and 19.0 m, respectively; p [log-rank] < 0.0001) and validation (median PFS, 11.3 m and 22.5 m, respectively; p [log-rank] = 0.0063) cohorts. CONCLUSIONS: A radiomics-based model was established to predict the risk of progression in hypopharyngeal cancer with chemoradiotherapy. KEY POINTS: • Clinical information showed limited performance in stratifying the risk of progression among patients with hypopharyngeal cancer. • Imaging features extracted from CECT and NCCT images were independent predictors of PFS. • We combined significant features and valuable clinical variables to establish a nomogram to predict individual risk of progression.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31673961

RESUMO

PURPOSE: Acute ischemic stroke is one of the most causes of death all over the world. Onset to treatment time is critical in stroke diagnosis and treatment. Considering the time consumption and high price of MR imaging, CT perfusion (CTP) imaging is strongly recommended for acute stroke. However, too much CT radiation during CTP imaging may increase the risk of health problems. How to reduce CT radiation dose in CT perfusion imaging has drawn our great attention. METHODS: In this study, the original 30-pass CTP images are downsampled to 15 passes in time sequence, which equals to 50% radiation dose reduction. Then, a residual deep convolutional neural network (DCNN) model is proposed to restore the downsampled 15-pass CTP images to 30 passes to calculate the parameters such as cerebral blood flow, cerebral blood volume, mean transit time, time to peak for stroke diagnosis and treatment. The deep restoration CNN is implemented simply and effectively with 16 successive convolutional layers which form a wide enough receptive field for input image data. 18 patients' CTP images are employed as training set and the other six patients' CTP images are treated as test dataset in this study. RESULTS: Experiments demonstrate that our CNN can restore high-quality CTP images in terms of structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR). The average SSIM and PSNR for test images are 0.981 and 56.25, and the SSIM and PSNR of regions of interest are 0.915 and 42.44, respectively, showing promising quantitative level. In addition, we compare the perfusion maps calculated from the restored images and from the original images, and the average perfusion results of them are extremely close. Areas of hypoperfusion of six test cases could be detected with comparable accuracy by radiologists. CONCLUSION: The trained model can restore the temporally downsampled 15-pass CTP to 30 passes very well. According to the contrast test, sufficient information cannot be restored with, e.g., simple interpolation method and deep convolutional generative adversarial network, but can be restored with the proposed CNN model. This method can be an optional way to reduce radiation dose during CTP imaging.

9.
Appl Opt ; 58(30): 8148-8152, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674484

RESUMO

In this work, we report a large-active-area multispectral superconducting nanowire single-photon detector for free-space applications. The detector is realized by fabricating NbTiN nanowire with an active area of 35 µm diameter on two serially connected dielectric mirrors that can simultaneously and efficiently detect single photons at the three typical wavelengths employed in free-space applications, namely, 532, 850, and 1064 nm. Maximal system detection efficiencies (SDEs) of 80.0% at 532 nm and 850 nm and 75.8% at 1064 nm are achieved for polarized light obtained by coupling the detector with an SMF-28 fiber. Upon coupling with a 50 µm multimode fiber, SDEs of 68.6%, 59.6%, and 47.0%, are achieved for 532, 850, and 1064 nm wavelength unpolarized light, respectively. Moreover, the detector shows timing jitters of 37.1 and 41.0 ps when coupled with SMF-28 fiber and 50 µm multimode fiber. This type of detector with a large active area and multiwavelength detection capability is promising for both single and multiwavelength free-space applications.

10.
Opt Express ; 27(21): 29567-29580, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684216

RESUMO

Nonlinear impairments induced by the opto-electronic components are one of the fundamental performance-limiting factors in high-speed optical short-reach communications, significantly hindering capacity improvement. This paper proposes to employ a kernel mapping function to map the signals in a Hilbert space to its inner product in a reproducing kernel Hilbert space, which has been successfully demonstrated to mitigate nonlinear impairments in optical short-reach communication systems. The operation principle is derived. An intensity modulation/direct detection system with 1.5-µm vertical cavity surface emitting laser and 10-km 7-core fiber achieving 540.68-Gbps (net-rate 505.31-Gbps) has been carried out. The experimental results reveal that the kernel mapping based schemes are able to realize comparable transmission performance as the Volterra filtering scheme even with a high order.

11.
Psychiatry Res ; : 112639, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31685286

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, but the genetic mechanism of ADHD remains elusive now. METHODS: Tissue specific transcriptome-wide association study (TWAS) of ADHD was performed by FUSION utilizing a genome-wide association study (GWAS) dataset of ADHD (including 20,183 ADHD cases and 35,191 healthy controls) and gene expression reference from brain and blood. Furthermore, the genes identified by TWAS were compared with the differently expressed genes detected by mRNA expression profiles of ADHD rat model and autism spectrum disorders (ASD) patients. Functional enrichment and annotation analysis of the identified genes were performed by DAVID and FUMAGWAS tool. RESULTS: For brain tissue, TWAS identified 148 genes with P value < 0.05, such as TDO2 (PTWAS=4.01×10-2), CHD1L (PTWAS=9.64×10-3) and KIAA0319L (PTWAS=4.05×10-4). Further 11 common genes were examined in the mRNA expression datasets, such as ACSM5 (PTWAS=3.62×10-2, PmRNA=0.005), CCDC24 (PTWAS=1.49×10-2, PmRNA=2.35×10-3) and MVP (PTWAS=5.55×10-3, PmRNA=5.40×10-3). Pathway enrichment analysis of the genes identified by TWAS detected 3 pathways for ADHD, including Other glycan degradation (P value=0.021), Viral myocarditis (P value=0.034) and Endocytosis (P value=0.041). CONCLUSIONS: Through integrating GWAS and mRNA expression data, we identified a group of ADHD-associated genes and pathways, providing novel clues for understanding the genetic mechanism of ADHD.

12.
Plant J ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692131

RESUMO

Chromosome painting is a powerful technique for chromosome and genome studies. We developed a flexible chromosome painting technique based on multiplex PCR of a synthetic oligonucleotide (oligo) library in cucumber (Cucumis sativus L., 2n=14). Each oligo in the library was associated with an universal as well as nested specific primers for amplification, which allow to generate different probes from the same oligo library. We were also able to generate double-strand-labeled oligos, which produced much stronger signals than single-strand-labeled oligos, by amplification using fluorophore-conjugated primer pairs. Oligos covering cucumber chromosome 1 (Chr1) and chromosome 4 (Chr4) consisting of eight segments were synthesized in one library. Different oligo probes generated from the library painted the corresponding chromosomes/segments unambiguously, especially on pachytene chromosomes. This technique was then applied to study the homoeologous relationships among cucumber, C. hystrix and C. melo chromosomes based on cross-species chromosome painting using Chr4 probes. We demonstrated that the probe was feasible to detect inter-species chromosome homoeologous relationships and chromosomal rearrangement events. Based on its advantages and great convenience, we anticipate that this flexible oligo-painting technique has great potential for the studies of the structure, organization, and evolution of chromosomes in any species with a sequenced genome.

13.
Medicine (Baltimore) ; 98(45): e17795, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702631

RESUMO

RATIONALE: Overactive bladder (OAB) is a common disease in the female urinary system. Refractory OAB is an indication for sacral neuromodulation (SNM) therapy, which was approved by the Food and Drug Administration (FDA) of the United States. However, SNM does not alleviate the clinical symptoms in all refractory OAB cases. Patients are required to undergo an SNM stage 1 operation, a traumatic and costly procedure, to evaluate the clinical efficacy of the treatment. If the procedure is predicted to likely be ineffective, the patient has to bear the physical and economic losses. Here, we report a patient with a 3-year course of refractory urge urinary incontinence who was treated with electroacupuncture according to traditional Chinese medicine (TCM). PATIENT CONCERNS: The patient was 73 years old and had frequent urination and urge urinary incontinence for 3 years; she had 24 to 30 counts of urination per day and 7 to 9 counts of urge incontinence. The patient was treated with multiple TCM and Western medicines and therapies. The TCM treatment consisted of several patented Chinese medicines and TCM decoctions. The Western medication comprised mainly antibiotics, alpha receptor antagonists, and muscarinic receptor antagonists. The treatment effect was unsatisfactory, and there was no apparent alleviation of symptoms; therefore, she underwent electroacupuncture. DIAGNOSIS: Refractory OAB. INTERVENTIONS: The patient received 30 days of TCM-based electroacupuncture with optimized acupoint positioning, which comprised a total of 10 sessions (1 electroacupuncture session every 2 days) targeting the bilateral Zhongliao and Sanyinjiao acupoints. After treatment, the patient experienced a good therapeutic outcome. OUTCOMES: After 30 days of electroacupuncture treatment, the average daily count of urination in 5 days decreased from 29.3 per day before treatment to 19.8 after treatment, and the average count of urge incontinence decreased from 9.3 before treatment to 5.8 after treatment. However, good prognosis was not stable. After careful consideration, the patient accepted SNM treatment, which greatly alleviated the symptoms of frequent urination and urge incontinence. The patient received follow-up visits for 2 years, during which she manifested stable curative effects. LESSONS: The optimized positioning at the Zhongliao acupoint improves the accuracy of acupuncture. Accurate electroacupuncture alleviates the symptoms of refractory OAB by stimulating the Zhongliao and Sanyinjiao acupoints, as the underlying mechanisms are similar to those of SNM. Therefore, it is possible to use electroacupuncture to estimate the therapeutic effect of SNM, thereby providing a reference for patients and clinicians to determine whether SNM treatment will be effective.

14.
Food Chem ; : 125667, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31679851

RESUMO

This research firstly investigated the inhibitory effect of isoquercitrin (ISQ) on Ovalbumin (OVA) glycation. The mechanism was elucidated through the interaction between OVA and ISQ, and changes in glycation sites and degree of each site as deduced by spectroscopy, spectrometry and molecular docking. ISQ significantly inhibited OVA glycation by attenuating the conformational change induced by glycation. It quenched the fluorescence of Trp via static mechanism, and exposed Trp residues to a more hydrophobic surroundings. Formation of OVA-ISQ complex was a endothermic processing driven by hydrophobic interactions, van der Waals forces and hydrogen bonds. LC-Orbitrap-MS/MS revealed that ISQ altered the location of glycation and alleviated the glycation degree of most sites. Molecular docking results indicated that ISQ inserted into the hydrophobic pocket of OVA with six hydrogen bonds and one π-π stacking formed between ISQ and the amino acid residues of OVA, leading to the altered glycation activity of some sites.

15.
J Nutr Sci Vitaminol (Tokyo) ; 65(5): 375-382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666473

RESUMO

Breast cancer is one of the most common cancers among women worldwide, and several studies have investigated the association of dietary patterns and breast cancer. However, findings of studies are inconclusive. Therefore, we aimed to conduct a meta-analysis to summarize the available data regarding the association of vegetable-fruit-soybean dietary pattern and breast cancer. A systematic literature search was conducted via PubMed, Web of Science and EMBASE to identify eligible cohort studies before February 2019. A total of 12 cohort studies were included in the meta-analysis. The summary relative risks (RR) with 95% CI were calculated with a fixed-effects model. The overall RR of breast cancer for the highest versus lowest intake of vegetable-fruit-soybean dietary pattern was 0.87 (95% CI, 0.82-0.91), with little heterogeneity (p=0.73, I2=0%). There was no obvious publication bias according to funnel plot and Begg's and Egger's test. In summary, the evidence from this meta-analysis indicates that vegetable-fruit-soybean dietary pattern was inversely associated with breast cancer. However, well-designed randomized controlled trials are needed to elicit the clear effect of vegetable-fruit-soybean dietary pattern and breast cancer. Women can reduce the risks of breast cancer by eating more fruits and vegetables and soybeans, which is a constructive suggestion.

16.
Chemosphere ; 242: 125168, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31678850

RESUMO

Plants have evolved effective strategies to cope with heavy metals Cd toxicity, but the regulatory mechanism underlying Cd tolerance and accumulation are still poorly understood. miR156 has been shown to be the master regulator of development and stress response in plants. However, whether miR156 is also involved in plant Cd stress response remains unknown. Here, we show that plants overexpressing miR156 (miR156OE) accumulated significantly less Cd in the shoot, and conferred enhanced tolerance to Cd stress. Plants with a knocked-down level of miR156 (MIM156) were sensitive to Cd stress, and accumulated significantly higher Cd. Under Cd stress, miR156OE had significantly longer primary root length, higher biomass and chlorophyll content, increased activities of antioxidative enzymes and lower levels of endogenous reactive oxygen species (ROS), while MIM156 had the opposite phenotype. To investigate the underlying mechanism of miR156-mediated Cd stress response in Arabidopsis, we profiled the expression of several Cd transporter genes. The expression of Cd uptake transporter of AtZIP1、AtZIP2 and vacuole segregated transporter AtABCC1 was significantly elevated in miR156OE, whereas it was significantly reduced in MIM156. MIM156 also led to an elevated level of AtHMA4 responsible for transporting Cd from the root to the shoot. Our results indicate that miR156 acts as a positive regulator of plant tolerance to Cd stress by modulating ROS levels and Cd uptake/transport genes expression. Therefore, our study adds a new layer of regulatory mechanism for Cd transport and tolerance in plants, and provides a perspective to regulate Cd transport artificially by modulating plant vegetative growth and development using miR156.

17.
BMC Neurol ; 19(1): 266, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684908

RESUMO

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

18.
BMC Cancer ; 19(1): 1037, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684910

RESUMO

BACKGROUND: SMAD4 is frequently inactivated and associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Abnormal SMAD4 expression also plays an important role in the malignant progression of PDAC. METHODS: We investigated SMAD4 status in PDAC by immunohistochemical methods to explore the relationships between SMAD4 expression and clinicopathological features and then detected SMAD4 mutations by Sanger sequencing in 95 patients with PDAC to identify new mutation sites in PDAC. We further evaluated the effects of a missense mutation, Y353C, in the SMAD4 MH2 domain, on cell proliferation and migration in vitro. RESULTS: Immunohistochemistry showed that the expression of SMAD4 in PDAC carcinoma tissue was significantly lower than that in normal pancreatic tissue, and negative SMAD4 expression was closely related to tumour diameter, staging, lymph node metastasis and differentiation. Sanger sequencing analysis showed that the rate of SMAD4 mutation was 11.8% in 85 PDAC cases, and the novel SMAD4 Y353C missense mutation identified in this study promoted cell migration and invasion without affecting cell proliferation in vitro. Furthermore, SMAD4 Y353C resulted in reduced expression of E-cadherin and increased expression of Vimentin compared with wild-type SMAD4 overexpression. CONCLUSION: This study supports the key role of SMAD4 as a tumour suppressor gene in PDAC and shows that SMAD4 Y353C is associated with poor progression of PDAC.

19.
Theranostics ; 9(25): 7648-7665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695792

RESUMO

Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous cell carcinoma (HNSC) is urgently required. Methods: Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed. Results: We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR < 0.001) signaling pathways. CASEs enriched in immune-related pathways were closely associated with immune cell infiltration and cytolytic activity. AS regulatory networks suggested a significant association between splicing factor (SF) expression and CASEs and might be regulated by SF methylation. Eighteen CASEs were identified as independent prognostic factors for overall and disease-free survival. Unsupervised clustering analysis revealed distinct correlations between AS-based clusters and prognosis, molecular characteristics and immune features. Immunogenic features and immune subgroups cooperatively depict the immune features of AS-based clusters. Conclusion: This comprehensive genome-wide analysis of the AS landscape in HNSC revealed novel AS events related to carcinogenesis and immune microenvironment, with implications for prognosis and therapeutic responses.

20.
Theranostics ; 9(25): 7807-7825, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695802

RESUMO

Peptide-based materials hold great promise as immunotherapeutic agents for the treatment of many malignant cancers. Extensive studies have focused on the development of peptide-based cancer vaccines and delivery systems by mimicking the functional domains of proteins with highly specific immuno-regulatory functions or tumor cells fate controls. However, a systemic understanding of the interactions between the different peptides and immune systems remains unknown. This review describes the role of peptides in regulating the functions of the innate and adaptive immune systems and provides a comprehensive focus on the design, categories, and applications of peptide-based cancer vaccines. By elucidating the impacts of peptide length and formulations on their immunogenicity, peptide-based immunomodulating agents can be better utilized and dramatic breakthroughs may also be realized. Moreover, some critical challenges for translating peptides into large-scale synthesis, safe delivery, and efficient cancer immunotherapy are posed to improve the next-generation peptide-based immunotherapy.

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