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1.
Br J Haematol ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068254

RESUMO

Dehydropeptidase-1 (DPEP1) is a zinc-dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B cell acute lymphoblastic leukaemia (ALL) is unknown. We found that in adults with common B cell ALL high DPEP1, transcript levels at diagnosis were independently associated with an increased cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels. We show an increased proliferation and prosurvival role of DPEP1 in B cell ALL cells via regulation of phosphCREB and p53, which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analysing DPEP1 transcript levels at diagnosis could help predict therapy outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B cell ALL.

2.
J Med Genet ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066630

RESUMO

BACKGROUND: Hirschsprung disease (HSCR) is a life-threatening congenital disorder in which the enteric nervous system is completely missing from the distal gut. Recent studies have shown that miR-4516 markedly inhibits cell migration, and as one of its potential targets, MAPK10 functions as a modifier for developing HSCR. We thus aimed to evaluate the role of miR-4516 and MAPK10 in HSCR and how they contribute to the pathogenesis of HSCR. METHODS: We examined 13 genetic variants using the MassArray system in a case-control study (n=1015). We further investigated miR-4516-mediated regulation of MAPK10 in HSCR cases and human neural cells, the effects of cis-acting elements in MAPK10 on miR-4516-mediated modulation and cell migration process. RESULTS: Three positive 3' UTR variants in MAPK10 were associated with altered HSCR susceptibility. We also showed that miR-4516 directly regulates MAPK10 expression, and this regulatory mechanism is significantly affected by the 3' UTR cis-acting elements of MAPK10. In addition, knock-down of MAPK10 rescued the effect of miR-4516 on the migration of human neural cells. CONCLUSION: Our findings indicate a key role of miR-4516 and its direct target MAPK10 in HSCR risk, and highlight the general importance of cis- and posttranscriptional modulation for HSCR pathogenesis.

3.
Br J Haematol ; 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32090321

RESUMO

Acute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate. This study established the value of mutations based on next-generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC-MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16-69) years. The 3-year cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as 'NGS low risk', which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as 'MRD high risk', which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post-treatment parameters. In CR2 and non-remission patients who underwent allo-HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post-treatment parameters. Relapsed patients still have a favourable outcome followed by allo-HSCT.

4.
Anal Chem ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32066237

RESUMO

Aberrant brown adipose tissue (BAT) metabolism is linked to obesity as well as other metabolic disorders. However, the paucity of imaging tools limits the study of in vivo BAT metabolism in animal models. The current work evaluated a heptamethine dye (CyHF-8) in living mice as a dual-modality BAT-avid molecular probe for two imaging approaches, including near-infrared fluorescence imaging (NIRF) and photoacoustic imaging (PAI). CyHF-8 exhibited favorable spectral properties in the near-infrared window (786/787/805 nm) and accumulated in the subcellular mitochondria of brown adipocytes. After intravenous injection of CyHF-8, NIRF and PAI were both capable of noninvasively detecting interscapular BAT at early time points in living mice. Quantitative analysis of NIRF and PAI images showed that CyHF-8 signals respond to dynamic BAT changes in mice stimulated by norepinephrine (NE) and in diabetic mice induced by streptozotocin (STZ). In summary, dual-modality NIRF/PAI probe CyHF-8 can be used for both NIRF and PAI to noninvasively assess BAT metabolism in living animals.

5.
Int Immunopharmacol ; 79: 106083, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31923823

RESUMO

The neuroinflammatory response induced by microglia plays a vital role in causing secondary brain damage after traumatic brain injury (TBI). Previous studies have found that the improved regulation of activated microglia could reduce neurological damage post-TBI. Phillyrin (Phi) is one of the main active ingredients extracted from the fruits of the medicinal plant Forsythia suspensa (Thunb.) with anti-inflammatory effects. Our study attempted to investigate the effects of phillyrin on microglial activation and neuron damage after TBI. The TBI model was applied to induce brain injury in mice, and neurological scores, brain water content, hematoxylin and eosin staining and Nissl staining were employed to determine the neuroprotective effects of phillyrin. Immunofluorescent staining and western blot analysis were used to detect nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ) expression and nuclear translocation, and the inflammation-related proteins and mRNAs were assessed by western blot analysis and quantitative real-time PCR. The results revealed that phillyrin not only inhibited the proinflammatory response induced by activated microglia but also attenuated neurological impairment and brain edema in vivo in a mouse TBI model. Additionally, phillyrin suppressed the phosphorylation of NF-κB in microglia after TBI insult. These effects of phillyrin were mostly abolished by the antagonist of PPARγ. Our results reveal that phillyrin could prominently inhibit the inflammation of microglia via the PPARγ signaling pathway, thus leading to potential neuroprotective treatment after traumatic brain injury.

6.
Eur J Med Chem ; 188: 112017, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926470

RESUMO

A series of xanthine compounds derived from the previous hit 20i with modification on the terminal side chain was discovered through ring formation strategy. Systematic optimization of the compounds with rigid heterocycles in the hydrophobic side chain led to the new lead compound HBK001 (21h) with the improved DPP-IV inhibition and moderate GPR119 agonism activity in vitro. As a continuing work to further study the PK and PD profiles, 21h and its hydrochloride (22) were synthesized on grams scale and evaluated on the ADME/T and oral glucose tolerance test (OGTT) in ICR mice. Compound 22 showed the improved bioavailability and blood glucose-lowering effect in vivo compared to its free base 21h probably attributed to its improved solubility and permeability. The preliminary toxicity studies on compound 22 exhibited that the result of mini-Ames was negative and the preliminary acute toxicity LD50 in mice was above 1.5 g/kg, while it showed moderate inhibition on hERG channel with IC50 4.9 µM maybe due to its high lipophilicity. These findings will be useful for the future drug design for more potent and safer dual ligand targeting DPP-IV and GPR119 for the treatment of diabetes.

7.
Oral Dis ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958204

RESUMO

OBJECTIVE: As an extracellular vesicle, exosomes can release from virus-infected cells containing various viral or host cellular elements and could stimulate recipient's cellular response. Enterovirus 71 (EV71), a single-strand positive-sense RNA virus, is known to cause hand, foot, and mouth disease (HFMD) in children and bring about severe clinical diseases. METHODS: Separated the human oral epithelial cells (OE cells) from normal buccal mucosa through enzyme digestion. Performed a comprehensive miRNA profiling in exosomes from EV71-infected OE cells through deep small RNA-seq. Using the Human Antiviral Response RT Profiler PCR Array profiles to explore the interactions of innate immune signaling networks with exosomal miR-30a. Knocked out the MyD88 gene in macrophages using CRISPR/Cas9-mediated genome editing method. RESULTS: Our study demonstrated that the miR-30a was preferentially enriched in exosomes that released from EV71-infected human oral epithelial cells through small RNA-seq. We found that the transfer of exosomal miR-30a to macrophages could suppress type Ⅰ interferon response through targeting myeloid differentiation factor 88 (MyD88) and subsequently facilitate the viral replication. CONCLUSIONS: Exosomes released from EV71-infected OE cells selectively packaged high level of miR-30a that can be functionally transferred to the recipient macrophages resulted in targeting MyD88 and subsequently inhibited type I interferon production in receipt cells, thus promoting the EV71 replication.

8.
Photochem Photobiol Sci ; 19(1): 49-55, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31793618

RESUMO

A dual-signal probe PPN based on the natural ß-pinene derivative nopinone was synthesized for the colorimetric detection of Cu2+ and ratiometric detection of Ag+. Upon the addition of Ag+, a significant fluorescence change from blue to green was observed with a low detection limit (0.86 µM). However, upon the addition of Cu2+, a significant color change from colorless to yellow was observed with a low detection limit (0.56 µM). The novel probe PPN was applied as a probe for the colorimetric detection of Cu2+ and ratiometric detection of Ag+ with a high selectivity, good sensitivity and fast response time. The detection mechanisms of probe PPN for Cu2+/Ag+ were confirmed by 1H NMR and HRMS-ESI. Besides, probe PPN could sense Cu2+/Ag+ on test strips. Additionally, probe PPN could be applied to quantitatively detect the concentration of Ag+ in water samples and image Ag+ in living cells.

9.
Ann Hematol ; 99(1): 73-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768677

RESUMO

For acute myeloid leukemia (AML) with nucleophosmin 1 mutation (NPM1m), multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) are used to monitor minimal residual disease (MRD). However, the results of the two methods are sometimes inconsistent. This study was designed to analyze how to address the discordant results of FCM and RQ-PCR in AML patients undergoing chemotherapy, especially when positive FCM (FCM+) and negative NPM1m (NPM1m-) results are detected in the same sample. Our study included 93 AML patients with NPM1m positive (NPM1m+) who received chemotherapy but did not undergo hematopoietic stem cell transplantation. We monitored NPM1m and leukemia-associated immunophenotypes (LAIPs) by RQ-PCR and FCM, respectively, to assess MRD after each chemotherapy course. After each course of chemotherapy, all patients were classified into four groups based on the results of FCM and RQ-PCR: both negative (group 1, FCM-NPM1m-), single positive (group 2, FCM-NPM1m+; group 3, FCM+NPM1m-), or both positive (group 4, FCM+NPM1m+). The results showed that there was not a significant difference in the 2-year cumulative incidence of relapse (CIR) after each course of chemotherapy between group 2 and group 3. Furthermore, patients in groups 2 and 3 had a lower 2-year CIR than those in group 4 and a significantly higher 2-year CIR than those in group 1 after the first two courses. The patients in group 4 had a significantly higher 2-year CIR than those in group 1 after the first two courses. These results suggested that in the MRD monitoring process of AML patients, when the results of FCM and RQ-PCR are inconsistent (especially when FCM is positive and NPM1m is negative), these single-positive results still have predictive significance for relapse.


Assuntos
Citometria de Fluxo , Leucemia Mieloide Aguda , Mutação , Proteínas de Neoplasias , Proteínas Nucleares , Reação em Cadeia da Polimerase em Tempo Real , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Neoplasia Residual , Proteínas Nucleares/sangue , Proteínas Nucleares/genética , Valor Preditivo dos Testes , Estudos Retrospectivos
10.
Arch Anim Nutr ; 74(1): 39-56, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31552757

RESUMO

The aim of the study was to investigate the effects of dietary alpha-ketoglutarate (AKG) on the faecal bacteria composition of suckling piglets after supplementation of AKG to the diet of lactating sows. After farrowing, the sows were assigned to either a normal lactation diet (control group, n = 12) or a diet supplemented with 0.25% AKG (AKG group, n = 12) based on body weight (BW) and parity. During the 21-d suckling period, BW and diarrhoea occurrences of piglets were recorded daily, while faeces were sampled weekly from sows and piglets. The levels of pH, ammonia, short-chain fatty acids (SCFA) and lactate in the faeces of piglets were determined. In particular, bacteria profiles in faeces of sows and their suckling piglets were examined by Illumina sequencing. The results showed that the AKG diet altered the faecal bacteria composition in sows during the 21-d lactation period, leading to increases (p < 0.05) in the abundances of genera Prevotella, Lactobacillus, Bacteroides and Methanobrevibacter, but decreases (p < 0.05) in the abundances of genera Oscillospira and Dorea. AKG supplement to the sows during lactation indirectly enhanced (p < 0.05) bacterial richness and SCFA levels (especially, acetate) in the faeces of piglets during the 21-d suckling period. It is suggested that maternal AKG supplementation alters the composition of faecal bacteria in the sows, and increases the faecal bacteria richness and acetate levels in the piglets, which might be associated with an enhanced growth performance of piglets.

11.
Food Chem Toxicol ; 135: 110936, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31682933

RESUMO

Palygorskite (PGS) is a kind of clay minerals with the property of absorbent capacity, and ginger essential oil (GEO) is a kind of natural antibacterial substances. In the present study PGS was used as carrier of GEO, and thus, a kind of new anti-bacterial composite GEO-PGS has been obtained. Characterization, inhibitory effect of GEO-PGS on Escherichia coli (E. coli) and its function of improvement of intestinal health would be investigated. Results showed that characterization analysis of GEO-PGS (FTIR, TG-DSC, BET, Zeta potential, specific surface area, total pore volume and size, TEM observation) demonstrated combination of GEO and PGS, and GEO was absorbed on the surface of PGS, partially filled the micropores of PGS. GEO-PGS had obvious inhibitory effect on E.coli, in combination of the antibacterial activity of GEO and bacteria-absorbed capability of PGS. GEO-PGS also had ameliorating effect on enteritis and intestinal dysfunction in vivo, which might be related to the inhibition of gene expression of inflammatory cytokines (TLR2, IL-6, TNFα, and IL-8). In conclusion, the novel composite GEO-PGS has the potential usage as functional component having effect of improving intestinal health.


Assuntos
Antibacterianos/uso terapêutico , Enterite/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Gengibre/química , Compostos de Magnésio/uso terapêutico , Óleos Voláteis/uso terapêutico , Compostos de Silício/uso terapêutico , Animais , Citocinas/genética , Citocinas/metabolismo , Sinergismo Farmacológico , Enterite/microbiologia , Expressão Gênica/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Camundongos , Testes de Sensibilidade Microbiana
12.
CNS Neurosci Ther ; 26(1): 101-116, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31179640

RESUMO

AIMS: Semaphorin7A (Sema7A) plays an important role in the immunoregulation of the brain. In our study, we aimed to investigate the expression patterns of Sema7A in epilepsy and further explore the roles of Sema7A in the regulation of seizure activity and the inflammatory response in PTZ-kindled epileptic rats. METHODS: First, we measured the Sema7A expression levels in patients with temporal lobe epilepsy (TLE) and in rats of a PTZ-kindled epilepsy rat model. Second, to explore the role of Sema7A in the regulation of seizure activity, we conducted epilepsy-related behavioral experiments after knockdown and overexpression of Sema7A in the rat hippocampal dentate gyrus (DG). Possible Sema7A-related brain immune regulators (eg, ERK phosphorylation, IL-6, and TNF-α) were also investigated. Additionally, the growth of mossy fibers was visualized by anterograde tracing using injections of biotinylated dextran amine (BDA) into the DG region. RESULTS: Sema7A expression was markedly upregulated in the brain tissues of TLE patients and rats of the epileptic model after PTZ kindling. After knockdown of Sema7A, seizure activity was suppressed based on the latency to the first epileptic seizure, number of seizures, and duration of seizures. Conversely, overexpression of Sema7A promoted seizures. Overexpression of Sema7A increased the expression levels of the inflammatory cytokines, IL-6 and TNF-α, ERK phosphorylation, and growth of mossy fibers in PTZ-kindled epileptic rats. CONCLUSION: Sema7A is upregulated in the epileptic brain and plays a potential role in the regulation of seizure activity in PTZ-kindled epileptic rats, which may be related to neuroinflammation. Sema7A promotes the inflammatory cytokines TNF-α and IL-6 as well as the growth of mossy fibers through the ERK pathway, suggesting that Sema7A may promote seizures by increasing neuroinflammation and activating pathological neural circuits. Sema7A plays a critical role in epilepsy and could be a potential therapeutic target for this neurological disorder.

14.
Laryngoscope ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800112

RESUMO

OBJECTIVES: Recent reports have identified autoimmune systemic diseases as a significant risk factor for sudden sensorineural hearing loss (SSNHL). We investigated whether systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were correlated with the hearing recovery of SSNHL. STUDY DESIGN: A retrospective study. METHODS: Records of 663 SSNHL patients between January 2008 and January 2019 were retrospectively reviewed, including demographic, comorbid diseases, and hearing recovery. Patients were divided into four groups (complete, partial, slight, and no recovery) according to Siegel's criteria and Chinese Medical Association of Otolaryngology (CMAO) criteria. Multinomial logistic regression was performed to evaluate the effects of onset of treatment, initial hearing threshold, audiogram pattern, diabetes mellitus, SLE, and RA on the prognosis of SSNHL according to both criteria. RESULTS: Patients in complete recovery, partial recovery, slight recovery, and no improvement were 95 (14.3%), 183 (27.6%), 170 (25.6%), and 215 (32.4%) by Siegel's criteria, and 90 (13.6%), 152 (22.9%), 188 (28.4%), and 233 (35.1%) by CMAO criteria, respectively. Among the four groups, onset of treatment, initial hearing threshold, diabetes mellitus, SLE, RA, and profound audiogram pattern were found to be associated with recovery outcome by both Siegel's criteria and CMAO criteria (P < .05). According to analysis results, presence of SLE, RA, diabetes mellitus and higher initial hearing threshold were significantly correlated with a poor prognosis by both Siegel's criteria and CMAO criteria (P < .05). CONCLUSION: Comorbid SLE or RA may negatively affect the prognosis of SSNHL. Lower initial hearing threshold and absence of diabetes mellitus are associated with favorable hearing recovery. LEVEL OF EVIDENCE: 4. Laryngoscope, 2019.

15.
Analyst ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834331

RESUMO

A novel fluorescent probe (OFN) based on nopinone for the detection of hypochlorite has been developed. The probe OFN exhibited a colorimetric and ratiometric response to hypochlorite with good selectivity, high sensitivity (the low detection limit is 0.136 µM) and fast response time (30 s). In response to ClO-, an obvious change was observed in both the fluorescence and absorption spectra, followed by the visible color change from colorless to yellow and the fluorescence color change from yellow to green. The sensing mechanism confirmed that the oxime group of OFN was oxidized to the aldehyde group, which was proved by HRMS and 1H NMR. What is more, the probe was used not only to detect the concentration of ClO- in water samples but also for monitoring ClO- in living cells.

16.
Sci Rep ; 9(1): 17601, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772301

RESUMO

To explore the differences in glucose-lipid metabolism profiles among the 3 TKIs, we designed a retrospective study to compare the onset of hyperglycaemia, hypertriglyceridemia, hypercholesterolemia and hyper-low density lipoprotein (LDL)-cholesterolemia in the patients with normal baseline glucose-lipid profiles and had no medical record of cardio- or cerebro-vascular diseases and/or metabolic syndrome diseases, and identify variables associated with them. 370 chronic myeloid leukaemia patients receiving dasatinib, nilotinib or imatinib therapy ≥3 months were retrospectively reviewed. During TKI-therapy, the mean fasting glucose, triglyceride, cholesterol, and LDL-cholesterol levels increased significantly in both dasatinib and nilotinib cohorts compared with the imatinib cohort. In multivariate analyses, dasatinib was the factor significantly associated with both poor hyperglycaemia- and hypertriglyceridemia-free survival. In addition, nilotinib was significantly associated with more occurrences of hyperglycaemia and hypercholesterolemia; increasing age was significantly associated with more occurrences of hyperglycaemia and hypertriglyceridemia. We concluded that dasatinib, similar to nilotinib, has the adverse impact on glucose-lipid metabolism compared with imatinib.

17.
Asian J Urol ; 6(4): 330-338, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31768318

RESUMO

Objective: To compare these managements focusing on the efficacy and safety to treat overactive bladder (OAB) in children through network meta-analysis (NMA). Methods: We searched PubMed, Embase, the Cochrane Library Central Register of Controlled Trials (CENTRAL) and the reference lists up to May 1st, 2017. Data from eligible randomized controlled trails (RCT) studies including three different treatment options were extracted. The primary outcome was maximal voiding volume (MVV). We performed pairwise meta-analyses by random effects model and NMA by Bayesian model. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess the quality of evidence contributing to each network estimate. Results: Six RCTs (462 patients) comparing three different interventions fulfilled the inclusion criteria. A low risk of bias was shown for the majority of the study items. The results of NMA showed that compared with antimuscarinic drugs, Parasacral transcutaneous electrical nerve stimulation was associated with significant improvement in the MVV (mean difference [MD] = 58.50, 95% confidential interval [CI]: 45.95-69.52), followed by urotherapy group (MD = 21.03, 95% CI: 11.85-29.97). When it comes to the constipation, antimuscarinic drugs exerted significant benefit than PTENS (odds ratio [OR]: 0.22, 95% CI: 0.01-0.46). No significant difference was found between other treatments. Conclusion: Compared with antimuscarinic drugs, PTENS was associated with significant better efficacy considering MVV, but more constipation events in de novo OAB children. Antimuscarinic drugs showed remarkably better efficacy considering MVV and comparable safety profile compared with urotherapy. Clinicians should take all known safety and compliance of patients into account when choosing an optimal strategy.

18.
Orphanet J Rare Dis ; 14(1): 237, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666091

RESUMO

BACKGROUND: Hirschsprung disease (HSCR) is an inherited congenital disorder characterized by the absence of enteric ganglia in the distal part of the gut. RET is the major causative gene and contains > 80% of all known disease-causing mutations. RESULTS: To determine the incidence of RET pathogenic variants, be they Mendelian inherited, mosaic in parents or true de novo variants (DNVs) in 117 Chinese families, we used high-coverage NGS and droplet digital polymerase chain reaction (ddPCR) to identify 15 (12.8%) unique RET coding variants (7 are novel); one was inherited from a heterozygous unaffected mother, 11 were DNVs (73.3%), and 3 full heterozygotes were inherited from parental mosaicism (2 paternal, 1 maternal): two clinically unaffected parents were identified by NGS and confirmed by ddPCR, with mutant allele frequency (13-27%) that was the highest in hair, lowest in urine and similar in blood and saliva. An extremely low-level paternal mosaicism (0.03%) was detected by ddPCR in blood. Six positive-controls were examined to compare the mosaicism detection limit and sensitivity of NGS, amplicon-based deep sequencing and ddPCR. CONCLUSION: Our findings expand the clinical and molecular spectrum of RET variants in HSCR and reveal a high frequency of RET DNVs in the Chinese population.

19.
Toxins (Basel) ; 11(11)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671876

RESUMO

Fusarium graminearum causes Fusarium head blight (FHB), a devastating disease of wheat. Salicylic acid (SA) is involved in the resistance of wheat to F. graminearum. Cell wall mannoprotein (CWM) is known to trigger defense responses in plants, but its role in the pathogenicity of F. graminearum remains unclear. Here, we characterized FgCWM1 (FG05_11315), encoding a CWM in F. graminearum. FgCWM1 was highly expressed in wheat spikes by 24 h after initial inoculation and was upregulated by SA. Disruption of FgCWM1 (ΔFgCWM1) reduced mannose and protein accumulation in the fungal cell wall, especially under SA treatment, and resulted in defective fungal cell walls, leading to increased fungal sensitivity to SA. The positive role of FgCWM1 in mannose and protein accumulation was confirmed by its expression in Saccharomyces cerevisiae. Compared with wild type (WT), ΔFgCWM1 exhibited reduced pathogenicity toward wheat, but it produced the same amount of deoxynivalenol both in culture and in spikes. Complementation of ΔFgCWM1 with FgCWM1 restored the WT phenotype. Localization analyses revealed that FgCWM1 was distributed on the cell wall, consistent with its structural role. Thus, FgCWM1 encodes a CWM protein that plays an important role in the cell wall integrity and pathogenicity of F. graminearum.

20.
Math Biosci Eng ; 16(6): 6536-6561, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31698575

RESUMO

Computer-aided detection or diagnosis (CAD) has been a promising area of research over the last two decades. Medical image analysis aims to provide a more efficient diagnostic and treatment process for the radiologists and clinicians. However, with the development of science and technology, data interpretation manually in the conventional CAD systems has gradually become a challenging task. Deep learning methods, especially convolutional neural networks (CNNs), are successfully used as tools to solve this problem. This includes applications such as breast cancer diagnosis, lung nodule detection and prostate cancer localization. In this overview, the current state-of-the-art medical image analysis techniques in CAD research are presented, which focus on the convolutional neural network (CNN) based methods. The commonly used medical image databases in literature are also listed. It is anticipated that this paper can provide researchers in radiomics, precision medicine, and imaging grouping with a systematic picture of the CNN-based methods used in CAD research.

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