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1.
Int J Biol Macromol ; 158: 493-501, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389652

RESUMO

Designing desirable adsorbent for highly efficient removal of heavy metal ions is of practical significance, given the cost-effectiveness, environmental benign, natural abundance and easy-handling collection features. Herein, a bead-like adsorbent with high adsorption capacity was prepared by modifying alginate beads using polyacrylate with high density of carboxyl groups. The developed alginate/polyacrylate beads were collaboratively characterized by FT-IR, TGA, SEM, XPS, etc., and various adsorption conditions were tested including the pH of the solution, contact time and the initial concentration. The experimental data were fitted well by the Freundlich isotherm model, and the maximum adsorption capacity was obtained from the Langmuir model was 611.0 mg/g, and adsorption process followed the Pseudo-second-order kinetic model. The adsorption mechanisms conformed to multi-layer adsorption, and mainly dominated by chemical interactions. The bead-like adsorbent exhibited excellent reusability after eight sequential cycles and displayed higher adsorption capacity towards lead ions. This type of adsorbent might possess promising role in treating heavy metals from water by virtue of degradable, cost-effective component and high adsorption efficiency.

3.
Psychoneuroendocrinology ; 117: 104690, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32417623

RESUMO

Ample evidence suggests that early life stress (ELS) is a high-risk factor for the development of visceral pain disorders, whereas the mechanism underlying neuronal circuit remains elusive. Herein, we employed neonatal colorectal distension (CRD) to induce visceral hypersensitivity in rats. A combination of electrophysiology, pharmacology, behavioral test, molecular biology, chemogenetics and optogenetics confirmed that CRD in neonatal rats could predispose the elevated firing frequency of the parvocellular corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of hypothalamus (PVN) in adulthood, with the CRH neurons activated and the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) diminished, both contributing to chronic visceral hypersensitivity. Moreover, following administration of exogenous GABA (300 mM/0.5 µL) and GABAA receptor agonist muscimol (3 mM/0.5 µL) in PVN, visceral hyperalgesia was abrogated. In addition, the PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), and the excitability of these GABAergic neurons was weakened in visceral hypersensitivity. Specific depletion of the GABAergic neurons in AV region precipitated visceral hyperalgesia. Moreover, chemogenetic activation of the PVN-projecting neurons alleviated the visceral hypersensitivity. Photoactivation of PVN-projecting GABAergic neurons abated the visceral hypersensitivity in neonatal-CRD rats, whereas photoinhibition evoked visceral hyperalgesia in naïve rats. Our findings demonstrated that disinhibition of the PVN-projecting GABAergic neurons in AV region contributed to the excitation of CRH neurons, thereby mediating visceral hypersensitivity. Our study might provide a novel insight into the neuronal circuits involved in the ELS-induced visceral hypersensitivity.

4.
Eur J Radiol ; 126: 108962, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32244066

RESUMO

PURPOSE: To evaluate the clinical benefits and complications of vesselplasty using the Mesh-Hold™ bone-filling container in the treatment of vertebral osteolytic fractures. METHODS: This was a retrospective study of patients with vertebral osteolytic pathological fractures treated by vesselplasty at Sichuan Cancer Hospital between 09/2014 and 01/2018. VAS1 (Visual analog scale) scores and ODI2 (Oswestry disability index) were recorded routinely 1 day preoperative, at 1 day, 1 month, 3 months, 6 months, and 1 year postoperation, and at the last follow-up. V13 (The of bone cement injection volume) and V24 (vertebral body osteolytic volume) were evaluated, and the R5 (ratio) of bone cement filling was obtained according to the V1/V2. RESULTS: Sixty-three patients were included (105 segments with osteolytic fractures). The amount of bone cement for each vertebra was 2.4-5.2 ml (3.1 ± 0.7 ml). The ratio (R) of bone cement filling was not related to pain relief or functional recovery (all P > 0.05).The VAS scores and ODI at different time points after surgery were decreased compared with before surgery (all P < 0.05). The bone cement leakage rate was 16.2 % (17/105). The follow-up was 4-30 months (mean of 13 ± 6 months). Thirty patients had died by the last follow-up, all from their cancer. CONCLUSIONS: The Mesh-Hold™ bone-filling container in the treatment of vertebral fractures induced by osteolytic metastases could reduce pain, improve function, and reduce the bone cement leakage rate in the process of vesselplasty.

5.
J BUON ; 25(1): 262-267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277640

RESUMO

PURPOSE: Drug resistance in lung cancer is a growing and challenging problem affecting the overall treatment and quality of the patient's life. The main purpose of the current study was to investigate the anticancer effects of flavokawain-B in gemcitabine-resistant non-small lung cancer cells (NSCLC) along with evaluating its mode of action by studying its effects on programmed cell death, ROS production, cell migration and invasion and PI3K/AKT signalling pathway. METHODS: Cell proliferation rate was studied using MTS cell viability assay while apoptosis induction by flavokawain-B was studied by fluorescence microscopy using DAPI staining as well as flow cytometry using Annexin V-FITC/propidium iodide (PI). Effects on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were studied by flow cytometry using Rh-123 and DCH-DA dyes respectively. Effects on cell migration and cell invasion were examined by in vitro wound healing assay and transwell assay respectively. Changes in PI3K/AKT protein expressions were evaluated by western blot. RESULTS: Flavokawain-B selectively inhibited the viability of the human NSCLC cell line A549, indicating lower toxicity compared with normal lung cancer (NLC) CCL-151 cells and both showed dose-dependent inhibition. DAPI and annexin V-FITC/PI staining showed that flavokawain-B led to a dose-dependent onset of apoptosis in lung cancer cells characterized by shrunken cells, fragmented nuclei and chromatin condensation. Western blot showed that flavokawain-B resulted in downregulation of Bcl-2 and upregulation of Bax in a dose dependent manner. Flavokawain-B treatment led to increase of intracellular ROS concentration and decrease of mitochondrial membrane potential (MMP) both showing dose-dependence. It also led to suppression of cell migration and invasion along with blocking PI3K/AKT signalling pathway. CONCLUSIONS: Flavokawain-B targets gemcitabine-resistant NSCLC cells selectively without inducing any significant toxicity in normal cells and these effects are mediated via apoptosis induction, ROS production, loss of MMP, suppression of cell migration and invasion and blocking PI3K/AKT signalling pathway.

7.
Front Genet ; 11: 198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218803

RESUMO

Prolyl endopeptidase-like (PREPL) deficiency (MIM 616224) is a very rare congenital disorder characterized by neonatal hypotonia and feeding difficulties, ptosis, neuromuscular symptoms, cognitive impairments, growth hormone deficiency, short stature, and hypergonadotropic hypogonadism. This syndrome is an autosomal recessive disease resulting from mutations in the PREPL gene. Previous reports have associated PREPL deficiency with only one nucleotide substitution, the deletion of four nucleotides, and eight small microdeletions in the PREPL gene In this study, we used whole exome sequencing (WES) to identify a novel homozygous splicing mutation (c.616 + 1G > T) in a 14-year-old Chinese girl with PREPL deficiency. Sequencing of the RT-PCR products from the patient's blood sample revealed that the c.616 + 1G > T variant disrupted normal splicing in intron 4 leading to an aberrant inclusion of 43 nucleotides in intron, a frameshift, and premature termination codon. Our patient exhibited several of the common phenotypes, including severe neonatal hypotonia, growth impairment and cognitive problems. However, we also observed several unusual phenotypic characteristics: absence of the ovaries, hypoplasia of the uterus, microcephaly and a short neck in patient is alsoobserved. These results provide further evidence for the involvement of PREPL development of the ovaries and uterus. Our findings may provide further insight into the relationship between the genotype and phenotype in collagen-associated diseases and improve the clinical diagnosis of Prolyl endopeptidase-like deficiency.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32186972

RESUMO

Background: Infection by multi-drug-resistant (MDR) bacteria is a high-risk factor for poor clinical results. Pancreatoduodenectomy (PD) has been associated with a high rate of complications, including intra-abdominal infections. However, there are few data available regarding MDR infection in patients undergoing PD. This study evaluated the present situation of risk factors for and clinical impact of MDR infection on patients who received PD. Methods: A total of 357 consecutive patients who underwent PD in our department from January 2016 to June 2018 were analyzed retrospectively. They were grouped into those with MDR infection (observation group) and those without MDR infection (control group). Univariable and multivariable analyses were used to identify risk factors for MDR infection in the two groups and the relations between MDR infection and clinical outcome. Results: Infections by MDR bacteria occurred in 38 patients (10.6%), and a total of 49 MDR bacterial strains were detected. Carbapenem-resistant Acinetobacter baumannii and MDR Pseudomonas aeruginosa were the most common strains. Multivariable analysis suggested that pancreatic fistula (p = 0.001) and post-operative use of quinolones (p = 0.000) were risk factors for MDR infection. At the same time, MDR infection was an independent risk factor for an increase in the 30-day in-hospital mortality rate (p = 0.005). Conclusions: Intensive intra-operative management to reduce the incidence of pancreatic fistula as well as curtailing empirical use of antibiotics, especially quinolones, may help to reduce the incidence of MDR infection and thus in-hospital deaths.

9.
J Sci Food Agric ; 100(8): 3507-3516, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32201949

RESUMO

BACKGROUND: There is an urgent need to strengthen the testing and certification of geographically iconic foods, as well as to use discriminatory science and technology for their regulation and verification. Multi-element and stable isotope analyses were combined to provide a new chemometric approach for improving the discrimination tea samples from different geographical origins. Different stoichiometric methods [principal component analysis (PCA), hierarchical cluster analysis (HCA), partial least squares-discriminant analysis (PLS-DA), back propagation based artificial neural network (BP-ANN) and linear discriminant analysis (LDA)] were used to demonstrate this discrimination approach using Yongchuanxiuya tea samples in an experimental test. RESULTS: Multi-element and stable isotope analyses of tea samples using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry easily distinguished the geographical origins. However, the clustering ability of the two unsupervised learning methods (PCA and HCA) were worse compared to that of the three supervised learning methods (PLS-DA, BP-ANN and LDA). BP-ANN and LDA, with 100% recognition and prediction abilities, were found to be better than PLS-DA. 86 Sr and 112 Cd were the markers enabling the successful classification of tea samples according to their geographical origins. Under the validation by 'blind' dataset, the prediction accuracies of the BP-ANN and LDA methods were all greater than 90%. The LDA method showed the best performance, with an accuracy of 100%. CONCLUSION: In summary, determination of mineral elements and stable isotopes using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry techniques coupled with chemometric methods, especially the LDA method, is a good approach for improving the authentication of a diverse range of tea. The present study contributes toward generalizing the use of fingerprinting mineral elements and stable isotopes as a promising tool for testing the geographic roots of tea and food worldwide. © 2020 Society of Chemical Industry.

10.
Strahlenther Onkol ; 196(4): 405, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32078694

RESUMO

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….

11.
Cancer Res ; 80(10): 1991-2003, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32098780

RESUMO

Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8+ T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8+ T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8+ T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8+ T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion-triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8+ T-cell infiltration and a reduced Th1/Th2 ratio. SIGNIFICANCE: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.

12.
Cell Res ; 30(3): 244-255, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32086476

RESUMO

Unlike most organs that mature during the fetal period, the male reproductive system reaches maturity only at puberty with the commencement of spermatogenesis. Robust modelling of human testicular organogenesis in vitro would facilitate research into mechanisms of and factors affecting human spermatogenic failure and male fertility preservation in prepubertal tumor patients. Here, we report successful recapitulation of human testicular organogenesis in vitro from fetal gonadal ridge. Our model displayed the formation of mature seminiferous epithelium and self-renewing spermatogonia. Remarkably, in vitro-derived haploid spermatids have undergone meiotic recombination, and showed increased genetic diversity as indicated by genetic analysis. Moreover, these spermatids were able to fertilize oocytes and support subsequent blastocyst formation. The in vitro testicular organogenesis system described here will play an important role in elucidating the regulation of human testis development and maintaining male fertility in prepubertal cancer patients.

13.
Sci Transl Med ; 12(531)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075946

RESUMO

MYCN-amplified neuroblastoma (NB) is characterized by poor prognosis, and directly targeting MYCN has proven challenging. Here, we showed that aldehyde dehydrogenase family 18 member A1 (ALDH18A1) exerts profound impacts on the proliferation, self-renewal, and tumorigenicity of NB cells and is a potential risk factor in patients with NB, especially those with MYCN amplification. Mechanistic studies revealed that ALDH18A1 could both transcriptionally and posttranscriptionally regulate MYCN expression, with MYCN reciprocally transactivating ALDH18A1 and thus forming a positive feedback loop. Using molecular docking and screening, we identified an ALDH18A1-specific inhibitor, YG1702, and demonstrated that pharmacological inhibition of ALDH18A1 was sufficient to induce a less proliferative phenotype and confer tumor regression and prolonged survival in NB xenograft models, providing therapeutic insights into the disruption of this reciprocal regulatory loop in MYCN-amplified NB.

14.
Strahlenther Onkol ; 196(2): 172-181, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784801

RESUMO

PURPOSE: The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT. METHODS: Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model. RESULTS: Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1­ and 2­year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4-40.1) and 22.0 (95% CI 16.4-27.5), while the 1­year, 3­year, and 5­year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20-0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32-0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29-0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003). CONCLUSION: Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.

15.
Radiology ; 294(1): 19-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746687

RESUMO

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval [CI]: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%; P = .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%; P = .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Bae in this issue.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Metástase Linfática/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Redes Neurais de Computação , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
16.
Cancer ; 126(4): 840-849, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31714592

RESUMO

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

17.
HPB (Oxford) ; 22(1): 91-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31262486

RESUMO

BACKGROUND: Synchronous resection of primary pancreatic ductal adenocarcinoma (PDAC) and liver metastases in highly selective patients is being accepted based on oncology research progress showing safe surgical outcomes with low morbidity and mortality. We also tried to determine patients who would benefit from the operation. METHODS: From January 2012 to October 2017, 48 patients who underwent synchronous resection of primary PDAC and liver metastases were retrospectively evaluated. Twenty-three of them underwent oligometastatic synchronous resection. RESULTS: The majority of synchronous resection PDAC patients underwent hepatic wedge resection, and no oligometastatic patient was treated with hemihepatectomy. The median overall survival (OS) of the synchronous resection patients was 7.8 months. Hepatic oligometastatic PDAC patients had a longer OS than that of non-oligometastatic synchronous resection patients, systemic chemotherapy patients and palliative patients (16.1 vs 6.4 months, P = 0.02; 16.1 vs 7.6 months, P = 0.02; 16.1 vs 4.3 months, P < 0.0001; respectively). Further analysis showed that localized pancreatic body/tail PDAC had a better OS in oligometastatic patients than in non-oligometastatic synchronous resection patients (16.8 months vs 7.05 months, P = 0.0004) and systemic chemotherapy patients (16.8 months vs 8 months, P = 0.003). CONCLUSION: Patients with pancreatic body/tail PDAC with liver oligometastases can benefit from synchronous resection.

18.
J Org Chem ; 85(4): 2716-2724, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31886664

RESUMO

Copper-catalyzed multicomponent borylacylation of imines with acid chlorides and bis(pinacolato)diboron was developed for the preparation of synthetically useful and pharmacologically relevant α-amino boronic acid derivatives. Starting from a range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and convenient one-pot, multistep access to the direct synthesis of α-amino boronic acid derivatives from available aldehydes and amines was also developed.

19.
Cell Death Dis ; 10(12): 948, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827081

RESUMO

Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation to carcinoma. Here, we explored the impact of NFAT5 on the biological behavior of PDAC and the underlying mechanism. We demonstrated that NFAT5 was highly expressed in PDAC and was related to poorer prognosis. Knockdown of NFAT5 lead to impaired proliferation of tumor cells caused by an aberrant Warburg effect. Mechanically, phosphoglycerate kinase 1 (PGK-1), which is the first enzyme generating ATP in glycolysis, was verified as a target gene of NFAT5. Over-expression of PGK1 compromised the aberrant oncological behavior caused by knockdown of NFAT5 both in vitro and in vivo. Clinical samples underwent positron emission tomography-computed tomography (PET-CT) examination and KrasG12D/+/Trp53R172H/+/Pdx1-Cre (KPC) mice were collected to support our conclusion.

20.
Nucleic Acids Res ; 47(22): 11755-11770, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31724724

RESUMO

During meiosis, telomere attachment to the inner nuclear envelope is required for proper pairing of homologous chromosomes and recombination. Here, we identified F-box protein 47 (FBXO47) as a regulator of the telomeric shelterin complex that is specifically expressed during meiotic prophase I. Knockout of Fbxo47 in mice leads to infertility in males. We found that the Fbxo47 deficient spermatocytes are unable to form a complete synaptonemal complex. FBXO47 interacts with TRF1/2, and the disruption of Fbxo47 destabilizes TRF2, leading to unstable telomere attachment and slow traversing through the bouquet stage. Our findings uncover a novel mechanism of FBXO47 in telomeric shelterin subunit stabilization during meiosis.

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