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1.
Biophys J ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32023436

RESUMO

Ribosomes are essential machines for protein synthesis in cells. Their structures are very complex but conserved in different species. Because most parts of a ribosome are composed of negatively charged RNAs, its electrostatics should play a fundamental role in the realization of its functions. However, a complete picture of the electrostatics of ribosomes is still absent at present. Here, assisted by the latest version of DelPhi (version 8.4), we illustrate a picture of the electrostatics of a prokaryotic ribosome as well as its molecular chaperones. The revealed electrostatics features are consistent with available experimental data as well as the functions of the ribosome and its molecular chaperones and provides a basis for further studying the mechanism underlying these functions.

2.
Cell Oncol (Dordr) ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32006253

RESUMO

PURPOSE: FAM83D has been proposed to act as an oncoprotein in several types of human cancer. Its role and mode of action in human non-small cell lung cancer (NSCLC) metastasis and its impact on chemotherapy are as yet, however, poorly understood. METHODS: FAM83D expression was measured in NSCLC cells and normal lung epithelial cells, as well as in primary NSCLC tissues and corresponding adjacent non-cancerous tissues, using qRT-PCR, Western blotting and immunohistochemistry. FAM83D was stably overexpressed in BEAS2B cells or silenced in A549 and H1299 cells using retroviral or lentiviral vectors. The growth capacity of NSCLC cells was evaluated using MTT and colony formation assays. Epithelial-mesenchymal transition (EMT) was assessed using Western blotting and immunofluorescence. NSCLC cell invasive capacities were assessed using scratch wound healing and Boyden chamber assays. NSCLC cell viability in response to cisplatin treatment was assessed using MTT assays in vitro and a xenograft model in vivo. RESULTS: We found that FAM83D expression levels were significantly elevated in NSCLC cells and tissues, and positively correlated with tumor progression and a poor prognosis. Exogenous FAM83D overexpression promoted, while FAM83D silencing inhibited NSCLC cell proliferation, EMT and invasion. FAM83D silencing also reduced cisplatin resistance. Concordantly, we found that NSCLC patients with a low FAM83D expression benefited most from chemotherapy. Mechanistically, we found that FAM83D activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Pharmacological treatment with either AKT or mTOR inhibitors reverted FAM83D-induced tumorigenic phenotypes. CONCLUSIONS: Our results suggest a role of FAM83D in NSCLC development. In addition, our results indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from AKT and/or mTOR inhibitor treatment.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32031326

RESUMO

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME) are standard treatments of stage II/III locally advanced rectal cancer (LARC), currently. Here, we evaluated the oncological outcomes in LARC patients treated with NACRT compared to TME alone, and determined whether tumor regression grade (TRG) and pathologic response after NACRT was related to prognosis. METHODS: This is a retrospective comparison of 358 LARC patients treated with either TME alone (non-NACRT group, n = 173) or NACRT plus TME (NACRT group, n = 185) during 2003-2013. Perioperative and oncologic outcomes, like overall survival (OS), disease-free survival (DFS) and recurrence were compared using 1:1 propensity score matching analysis. RESULTS: A total of 133 patients were matched for the analysis. After a median follow-up of 45 months (8-97 months), the 5-year OS (NACRT vs non-NACRT: 75.42% vs 72.76%; P = 0.594) and 5-year DFS (NACRT vs non-NACRT: 74.25% vs 70.13%; P = 0.224) were comparable between NACRT and non-NACRT, whereas the 5-year DFS rate was higher in the NACRT group when only stage IIIb/IIIc patients were considered (NACRT vs. non-NACRT: 74.79% vs. 62.29%; P = 0.056). In the NACRT group of 185 patients, those with pCR/stage I (vs stage II/stage III disease) or TRG3/TRG4 disease (vs TRG0/TRG1/TRG2) had significantly better prognosis. CONCLUSION: NACRT might provide survival benefit in patients with stage IIIb/IIIc locally advanced rectal cancer.

5.
Chemistry ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32078190

RESUMO

Novel lithium-lanthanide (lanthanide shortened as Ln: cerium and praseodymium) bimetallic coordination polymers of the formula C10H2LnLiO8(Ln: Ce named as CeLipmaand Pr named as PrLipma) and C10H3CeO8(named as Cepma) were prepared by a simplehydrothermal method. The 3 compounds were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), single crystal X-ray diffraction (SXRD), scanning electron microscopy (SEM), transmission electron microscope (TEM) andX-ray photoelectron spectroscopy(XPS). The results of the structural refinement show that they belong to triclinic symmetry and P-1 space group with cerium (or praseodymium) and lithium cations forming coordination bonds to oxygen atoms from different pyromellitic acid molecules and constructing into three-dimensional (3D) structures, it is interesting of the frameworks to exclude any coordination water and lattice water. As an electrode material for lithium ion batteries, CeLipma exhibits a maximum capacity of 800.5 mAh/g and a retention of 91.4% after 50 cycles at a current density of 100 mA/g. The favorable electrochemical properties of the lanthanide coordination polymers show potential application prospect in the field of electrode materials.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32049939

RESUMO

STUDY DESIGN: A retrospective study of 257 normal children at a single center from July 2016 to November 2018 was performed. OBJECTIVE: To evaluate the spinopelvic parameters in a population of normal children and adolescents in mainland China. SUMMARY OF BACKGROUND DATA: Values for sagittal parameters of the spine vary significantly by ages and different population. No study has yet quantified the normal measures for children and adolescents in China, or how these measures compare to other populations. METHODS: Pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK, T5-T12), lumbar lordosis (LL, L1-S1) and sagittal vertical axis (SVA) were measured and evaluated by whole spine AP&lateral X-ray images. RESULTS: A total of 257 subjects, including 116 boys (45%) and 141 girls (55%) aged 3-12 years, were enrolled. Correlation matrix analysis demonstrated that sagittal balance are strongly correlated with age and Risser sign, including PI, a reported fixed parameter. Further investigation showed that PI could be expressed by the equation PI = 26.243+1.153*age. CONCLUSIONS: PI was not a fixed but a dynamic parameter in the population under 12 years old. Indeed, PI increases with age and bone maturity in childhood. We also found lower PI, PT and SS compared with published studies of adolescents in other countries. These results may aid in the treatment of patients with spinal deformity, to help them achieve a certain degree of sagittal spinopelvic balance. LEVEL OF EVIDENCE: 2.

7.
BMC Neurosci ; 21(1): 7, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050908

RESUMO

BACKGROUND: It is a crucial task of brain science researches to explore functional connective maps of Biological Neural Networks (BNN). The maps help to deeply study the dominant relationship between the structures of the BNNs and their network functions. RESULTS: In this study, the ideas of linear Granger causality modeling and causality identification are extended to those of nonlinear Granger causality modeling and network structure identification. We employed Radial Basis Functions to fit the nonlinear multivariate dynamical responses of BNNs with neuronal pulse firing. By introducing the contributions from presynaptic neurons and detecting whether the predictions for postsynaptic neurons' pulse firing signals are improved or not, we can reveal the information flows distribution of BNNs. Thus, the functional connections from presynaptic neurons can be identified from the obtained network information flows. To verify the effectiveness of the proposed method, the Nonlinear Granger Causality Identification Method (NGCIM) is applied to the network structure discovery processes of Spiking Neural Networks (SNN). SNN is a simulation model based on an Integrate-and-Fire mechanism. By network simulations, the multi-channel neuronal pulse sequence data of the SNNs can be used to reversely identify the synaptic connections and strengths of the SNNs. CONCLUSIONS: The identification results show: for 2-6 nodes small-scale neural networks, 20 nodes medium-scale neural networks, and 100 nodes large-scale neural networks, the identification accuracy of NGCIM with the Gaussian kernel function was 100%, 99.64%, 98.64%, 98.37%, 98.31%, 84.87% and 80.56%, respectively. The identification accuracies were significantly higher than those of a traditional Linear Granger Causality Identification Method with the same network sizes. Thus, with an accumulation of the data obtained by the existing measurement methods, such as Electroencephalography, functional Magnetic Resonance Imaging, and Multi-Electrode Array, the NGCIM can be a promising network modeling method to infer the functional connective maps of BNNs.

8.
Nat Commun ; 11(1): 934, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071315

RESUMO

α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83+/- mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32013019

RESUMO

Accelerated urbanization has changed land use patterns, leading to the deterioration of ecosystems. Assessments of ecosystem health (ESH) during the urbanization process are used to determine the reasons and mechanism for this, and to uncover negative factors. In this study, we assessed the ESH of Qiannan prefecture, in Guizhou Province, China, based on the ecosystem services value. We selected a series of indicators, including natural, social, and economic aspects, to detect the impact of urbanization on ecosystem services in 1990, 1995, 2000, 2005, 2010, and 2015. The results show that ESH in Qiannan declined from 1990 to 2015, especially in the eastern and northern regions. Further, the results indicate that urbanization had a negative impact on ESH, of which the dominant factor was the proportion of construction land from 1990 to 2005. After 2005, moreover, the dominant factor was the gross domestic product. The impact of urbanization on EHS had spatial differences, however. The most significant negative impact was found in the east and north. After 2010, the western and central regions of Qiannan showed an urbanization trend in favor of ecosystem health. We recommend ecological restoration in regions with weak and relatively weak ESH levels to achieve sustainable development.

10.
Inorg Chem ; 59(2): 960-963, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31913025

RESUMO

Treatment of [Ir(PPh3)3Cl] with 2-[5-(pyridin-2-yl)-1H-pyrrol-2-yl]pyridine (Hdpp) in refluxing toluene affords an unexpected pyrrole-metalated iridium(III) hydride complex, [Ir(K2C,N-dpp)(H)(Cl)(PPh3)2] (1), via Cpyrrole-H activation, while the presence of the base KOtBu as the deprotonation reagent produces a pyridine-metalated iridium(III) hydride complex, [Ir(K3C,N,N-dpp)(H)(PPh3)2] (2), via Cpyridine-H activation. Treatment of [Ir(PPh3)3Cl] prepared by a convenient method with Hdpp in the presence of KOtBu under the refluxing mixture solvent toluene/methanol (2:1, v/v) generates the N,N-chelating complex [Ir(K2N,N-dpp)(H)(Cl)(PPh3)2] (3) together with 1 and the N,N-chelating dihydride complex [Ir(K2N,N-dpp)(H)2(PPh3)2] (4). Complex 4 is also readily produced by the reaction of [Ir(PPh3)3Cl] and Hdpp in the presence of KOtBu under refluxing methanol or by the reaction of IrCl3 and PPh3 in refluxing 2-ethoxyethanol. Complexes 1-4 are fully characterized by NMR, IR, and UV-vis spectroscopy and X-ray diffraction analysis. The dpp-/dpp2- ligand shows rich coordination capability, of which pyridine- and pyrrole-cyclometalated coordination modes are first reported. The formation of structural isomers 1 and 3 involved the selective activation of the C-H and N-H bonds of Hdpp is rationalized by theoretical calculations.

11.
Molecules ; 25(3)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991808

RESUMO

Four new diterpenoids, named aspidoptoids A-D (1-4), together with two known analogues (5-6) were isolated from Aspidopterys obcordata vine. Aspidoptoids A-B (1-2) are the first examples of phenylethylene-bearing 20-nor-diterpenoids of which aspidoptoid B (2) possesses a rare 3,10-oxybridge. Their structures and absolute configuration were determined by extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR) and electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their cytotoxic activities and inhibitory effects on the nitric oxide (NO) production.

12.
Chem Commun (Camb) ; 56(8): 1219-1222, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31895373

RESUMO

To monitor delicate changes of biological HOCl in vivo, a new probe (OH-substituted coumarin-hemicyanine, probe 2) was synthesized for NIR and ratiometric HOCl detection. Selectivity studies indicated that the electron-donating group (OH) substituted on the indolium moiety enhanced the selectivity to detect HOCl. With HOCl, the probe showed a ratiometric fluorescence (I500/I650) with a low detection limit (49.1 nM) and a rapid response (within 2 min). In addition, probe 2 was successfully applied to visualize exogenous and endogenous HOCl in living cells and animals and exhibited a perfect mitochondria target ability. This probe has been further studied as a potential and powerful tool to probe HOCl in arthritis models.


Assuntos
Cumarínicos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Indóis/química , Animais , Artrite/induzido quimicamente , Artrite/diagnóstico , Carragenina , Cumarínicos/síntese química , Cumarínicos/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Indóis/síntese química , Indóis/toxicidade , Limite de Detecção , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Mitocôndrias/metabolismo , Células RAW 264.7 , Espectrometria de Fluorescência/métodos , Peixe-Zebra
13.
Artigo em Inglês | MEDLINE | ID: mdl-31948076

RESUMO

Pollutant analysis and pollution source tracing are critical issues in air quality management, in which correlation analysis is important for pollutant relation modeling. A dynamic correlation analysis method was proposed to meet the real-time requirement in atmospheric management. Firstly, the spatio-temporal analysis framework was designed, in which the process of data monitoring, correlation calculation, and result presentation were defined. Secondly, the core correlation calculation method was improved with an adaptive data truncation and grey relational analysis. Thirdly, based on the general framework and correlation calculation, the whole algorithm was proposed for various analysis tasks in time and space, providing the data basis for ranking and decision on pollutant effects. Finally, experiments were conducted with the practical data monitored in an industrial park of Hebei Province, China. The different pollutants in multiple monitoring stations were analyzed crosswise. The dynamic features of the results were obtained to present the variational correlation degrees from the proposed and contrast methods. The results proved that the proposed dynamic correlation analysis could quickly acquire atmospheric pollution information. Moreover, it can help to deduce the influence relation of pollutants in multiple locations.

14.
Pathol Res Pract ; 216(2): 152785, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31889588

RESUMO

The relationship between integrin beta 4 (ITGB4) expression and laryngeal squamous cell carcinoma (LSCC) remains unclarified. The object of the present study was to explore the clinical significance and potential molecular mechanism of ITGB4 in LSCC. The protein level of ITGB4 was significantly higher in 46 LSCC patients than in 26 non-LSCC tissues detected by in-house immunohistochemistry. Consistently, ITGB4 mRNA level was also greatly upregulated based on microarray and RNA-seq data (standard mean difference, SMD = 1.62, 95 % CI: 1.23-2.00). And the area under curves (AUC) of summary receiver operator characteristic (SROC) was 0.87 (95 % CI: 0.84-0.90) based on 172 cases of LSCC and 59 cases of non-cancerous controls. Ninety genes were intersected by the ITGB4 related genes and LSCC differential expressed genes (DEGs) from all available microarray and RNA-seq datasets. Based on Gene Ontology (GO) analysis, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) for the 90 ITGB4 related DEGs were extracellular matrix organization, basement membrane and extracellular matrix structural constituent, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that ITGB4 related DEGs mainly participated in the pathways of ECM-receptor interaction, Focal adhesion and Small cell lung cancer. Moreover, the Protein-Protein Interaction (PPI) network indicated that ITGA3, ITGA5, ITGB4, MET, LAMA3, and COL4A1 might be the core genes of LSCC development related to ITGB4. In conclusion, high ITGB4 expression may lead to the occurrence and development of LSCC via various signaling pathways.

15.
Plant Mol Biol ; 102(4-5): 389-401, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894456

RESUMO

KEY MESSAGE: This study revealed that the Arabidopsis UGT75B1 plays an important role in modulating ABA activity by glycosylation when confronting stress environments. The cellular ABA content and activity can be tightly controlled in several ways, one of which is glycosylation by family 1 UDP-glycosyltransferases (UGTs). Previous analysis has shown UGT75B1 activity towards ABA in vitro. However, the biological role of UGT75B1 remains to be elucidated. Here, we characterized the function of UGT75B1 in abiotic stress responses via ABA glycosylation. GUS assay and qRT-PCR indicated that UGT75B1 is significantly upregulated by adverse conditions, such as osmotic stress, salinity and ABA. Overexpression of UGT75B1 in Arabidopsis leads to higher seed germination rates and seedling greening rates upon exposure to salt and osmotic stresses. In contrast, the big UGT75B1 overexpression plants are more sensitive under salt and osmotic stresses. Additionally, the UGT75B1 overexpression plants showed larger stomatal aperture and more water loss under drought condition, which can be explained by lower ABA levels examined in UGT75B1 OE plants in response to water deficit conditions. Consistently, UGT75B1 ectopic expression leads to downregulation of many ABA-responsive genes under stress conditions, including ABI3, ABI5 newly germinated seedlings and RD29A, KIN1, AIL1 in big plants. In summary, our results revealed that the Arabidopsis UGT75B1 plays an important role in coping with abiotic stresses via glycosylation of ABA.

16.
Colloids Surf B Biointerfaces ; 188: 110772, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31999965

RESUMO

This study aimed to develop sheddable polyethylene glycol (PEG) shells with TAT-modified core cross-linked nanomicelles as drug-delivery carriers of doxorubicin (DOX) to establish a programmed response against the tumor microenvironment, enhanced endocytosis, and lysosomal pH-triggered DOX release. First, poly(L-succinimide) (PSI) underwent a ring-opening reaction with ethylenediamine to generate poly(N-(2-aminoethyl)-l-aspartamide) (P(ae-Asp)). Next, the thiolytic cleavable PEG, 3,4-dihydroxyphenylacetic acid, and TAT were grafted onto P(ae-Asp) to synthesize the amphiphilic graft copolymer of mPEG-SS-g-P(ae-Asp)-MCA-DA-TAT. In aqueous solution, the amphiphilic polymer self-assembled into nanomicelles, encapsulating DOX into the hydrophobic core of micelles. TAT was shielded by the PEG corona during circulation to avoid non-specific transmembrane interaction with normal cells, while the tumor redox environment-responsive shedding of PEG could expose TAT to promote internalization of tumor cells. In order to improve the stability of nanomicelles and achieve pH-triggered drug release, a core cross-linking strategy based on the coordination of catechol and Fe3+ was adopted. In vitro studies demonstrated that core cross-linked nanomicelles maintained the nanostructure in 100 times dilution in pH 7.4 phosphate-buffered saline (PBS). Moreover, DOX release from DOX-loaded core cross-linked nanomicelles (DOX-TAT-CCLMs) was favored at simulated lysosomal conditions over simulated plasma conditions, indicating that these nanomicelles demonstrate characteristics of pH-triggered DOX release. The TAT modification considerably enhanced the mean fluorescence intensity of the nanomicelles endocytosed by MCF-7/ADR cells by 8 times, compared with DOX·HCl after 8 h of incubation. Notably, the IC50 value of nanomicelles (11.61 ±â€¯0.95 µg/mL) was nearly 4 times lower than that of DOX·HCl against MCF-7/ADR cells, implying that the nanomicelles could overcome drug resistance observed in MCF-7/ADR cells. Furthermore, the DOX-TAT-CCLMs reported superior tumor growth suppression in a 4T1 tumor-bearing mouse model. Thus, the redox- and pH- stimuli stepwise-responsive novel nanomicelles fabricated from the mPEG-SS-g-P(ae-Asp)-MCA-DA-TAT graft copolymer exhibited multifunctionality and displayed great potential for drug delivery.

17.
Sensors (Basel) ; 20(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948060

RESUMO

The control effect of various intelligent terminals is affected by the data sensing precision. The filtering method has been the typical soft computing method used to promote the sensing level. Due to the difficult recognition of the practical system and the empirical parameter estimation in the traditional Kalman filter, a neuron-based Kalman filter was proposed in the paper. Firstly, the framework of the improved Kalman filter was designed, in which the neuro units were introduced. Secondly, the functions of the neuro units were excavated with the nonlinear autoregressive model. The neuro units optimized the filtering process to reduce the effect of the unpractical system model and hypothetical parameters. Thirdly, the adaptive filtering algorithm was proposed based on the new Kalman filter. Finally, the filter was verified with the simulation signals and practical measurements. The results proved that the filter was effective in noise elimination within the soft computing solution.

18.
Sleep Breath ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919715

RESUMO

OBJECTIVE: A new index, approximate entropy (ApEn) of oxygen saturation, was used to assess the severity of hypoxemia in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), determine the correlation with other parameters, and explore its clinical value. METHODS: A retrospective analysis was performed on 1200 patients with OSAHS and snorers (normal control). All subjects underwent sleep apnea monitoring for 6 h. Subjects were divided into four subgroups by apnea-hypopnea index (AHI): normal control (AHI < 5), mild OSAHS (5 ≤ AHI < 15), moderate OSAHS (15 ≤ AHI < 30), and severe OSAHS 104 (AHI ≥ 30). ApEn was initially compared among the subgroups. Then a correlation analysis of AHI with ApEn and a correlation analysis of ApEn with oxygen desaturation index (ODI), lowest oxygen saturation (LO2), and T < 90% were performed. (2) The AHI was used as the gold standard, and an attempt was performed to determine the value of ApEn to assess the severity of hypoxemia in OSAHS. RESULTS: Among the 1200 subjects, 822 subjects were men (72%) and mean age was 53.2 ± 15.2 years (range 24-95 years). The ApEn in each group was significantly different (P <0.001), and the ApEn synchronously increased with AHI. Furthermore, a significant difference in ApEn was found among the groups (P <0.001). In addition, ApEn had a good correlation with ODI, LO2, and T <90%. According to the ROC analysis results, the boundary value of ApEn to judge OSAHS patients with mild, moderate, and severe hypoxia was 16.72, 17.84, and 20.06, respectively. CONCLUSION: ApEn synchronously increased with the AHI and had a good correlation with AHI, ODI, LO2, and T <90%. These findings suggest that ApEn may have clinical value for assessing hypoxia severity in OSAHS patients.

19.
World J Surg Oncol ; 18(1): 2, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898548

RESUMO

BACKGROUND: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. METHODS: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. RESULTS: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. CONCLUSIONS: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.

20.
Bioorg Chem ; 94: 103413, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791679

RESUMO

A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced ß-amyloid (Aß) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7 nM for hAChE and 0.66 µM for hBuChE) and the good Aß aggregation inhibition (49.2% at 20 µM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Aß-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.

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