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1.
Genomics ; 116(5): 110889, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901654

RESUMO

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

2.
BMC Cancer ; 24(1): 1006, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138436

RESUMO

BACKGROUND: FGFR genomic aberrations occur in approximately 5-10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. METHODS: Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. RESULTS: Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7-63.6); the median progression-free survival was 5.6 months (95% CI, 3.6-12.7) and median overall survival was 40.2 months (95% CI, 12.4-not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5-57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). CONCLUSIONS: Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Colangiocarcinoma , Pirazóis , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Adulto , Quinoxalinas/uso terapêutico , Quinoxalinas/administração & dosagem , Quinoxalinas/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/genética , Povo Asiático , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Intervalo Livre de Progressão , Idoso de 80 Anos ou mais
3.
Ann Hematol ; 103(6): 1989-2001, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38233570

RESUMO

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.


Assuntos
Anticorpos Monoclonais , Linfoma Extranodal de Células T-NK , Humanos , Anticorpos Monoclonais/uso terapêutico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/imunologia , Masculino , Feminino , ADP-Ribosil Ciclase 1 , Pessoa de Meia-Idade , Idoso , Adulto , Glicoproteínas de Membrana
4.
Chemistry ; 29(26): e202300055, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-36807385

RESUMO

Nanolobatone A, featuring an unprecedented tricyclo[10.3.0.01,2 ]pentadecane carbon skeleton, along with four new polyoxygenated and four unusual endoperoxide-bridged casbane-type diterpenoids were isolated from the Hainan soft coral Sinularia nanolobata. The structures of the new compounds were established by extensive spectroscopic analysis, X-ray diffraction analysis, and time-dependent density functional theory/electronic circular dichroism calculations. A plausible biosynthetic pathway of new isolates was proposed. Bioassays revealed that nanolobatone A showed weak antibacterial activity against the Gram-positive bacteria Streptococcus pyogenes.


Assuntos
Antozoários , Diterpenos , Animais , Estrutura Molecular , Antozoários/química , Diterpenos/química , Dicroísmo Circular , Cristalografia por Raios X
5.
Dig Dis Sci ; 68(4): 1605-1614, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36227429

RESUMO

BACKGROUND: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.


Assuntos
Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Hepatite B , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Hepatite B/complicações , Hepatite B/epidemiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Fígado Gorduroso/complicações , Alanina Transaminase , Diabetes Mellitus Tipo 2/complicações
6.
Zhongguo Zhong Yao Za Zhi ; 48(2): 321-328, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36725221

RESUMO

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.


Assuntos
Microbioma Gastrointestinal , Insuficiência Renal Crônica , Humanos , Medicina Tradicional Chinesa , Insuficiência Renal Crônica/tratamento farmacológico
7.
J Org Chem ; 87(22): 15608-15617, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36321171

RESUMO

This article presents an exploration of stereospecificity and divergent reactivity of Pd-catalyzed α,α-disubstituted alkenyl hydrazones to synthesize 1,4-dienes in the Z configuration and vinylcyclopropane. We calculated the energy profiles of four α,α-disubstituted alkenyl hydrazones. The results show that the energy profiles of the whole catalytic cycle are basically the same before the syn-carbopalladation step. Subsequent syn-ß-C elimination yields skipping dienes, or direct ß-H elimination yields vinylcyclopropane. Current theoretical calculations reveal that the stereospecificity and the divergent reactivity of reactions result from the competition between syn-ß-C elimination and ß-H elimination. The C-C bond rotation and subsequent syn-ß-C elimination step control the stereospecificity of the reaction by changing the olefin stereostructure from E to Z configuration. The steric factor of α-substituted groups mediates the transformation between syn-ß-C elimination and ß-H elimination. The results are of great significance for the scientific design of substrates to achieve accurate synthesis of target products.


Assuntos
Hidrazonas , Paládio , Paládio/química , Estereoisomerismo , Alcenos/química , Catálise
8.
BMC Cardiovasc Disord ; 22(1): 307, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799104

RESUMO

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.


Assuntos
Insuficiência Cardíaca , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Fatores de Risco
9.
Anal Chem ; 93(20): 7499-7507, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33980009

RESUMO

The development of a sensing platform with high sensitivity and specificity, especially programmability and universal applicability, for the detection of clinically relevant molecules is highly valuable for disease monitoring and confirmation but remains a challenge. Here, for the first time, we introduce the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system into an immobilization-free electrochemical biosensing platform for sensitively and specifically detecting the disease-related nucleic acids and small molecules. In this strategy, a modular rolling circle amplification (RCA) is designed to transform and amplify the target recognition event into the universal trigger DNA strand that is used as the trigger to activate the deoxyribonuclease activity of CRISPR/Cas12a for further signal amplification. The cleavage of the target-activated blocker probe allows the methylene blue-labeled reporter probes to be captured by the reduced graphene oxide-modified electrode, leading to an obviously increased electrochemical signal. We only need to simply tune the sequence for target recognition in RCA components, and this strategy can be flexibly applied to the highly sensitive and specific detection of microRNAs, Parvovirus B19 DNA, and adenosine-5'-triphosphate and the calculated limit of detection is 0.83 aM, 0.52 aM, and 0.46 pM, respectively. In addition, we construct DNA logic circuits (YES, NOT, OR, AND) of DNA inputs to experimentally demonstrate the modularity and programmability of the stimuli-responsive RCA-CRISPR/Cas12a system. This work broadens the application of the CRISPR/Cas12a system to the immobilization-free electrochemical biosensing platform and provides a new thinking for developing a robust tool for clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA/genética
10.
Technol Soc ; 64: 101514, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33424061

RESUMO

The continuous spread of the COVID-19 pandemic is causing people to feel anxiety and stress. This study constructs a four-layer research model to examine how a 360° virtual tour can reduce people's psychological stress through two types of presence (the sense of presence and telepresence) and affective-motivational states (enjoyment and involvement) in this extraordinary period of the COVID-19 pandemic. In order to test the moderating effect of involvement, partial least squares (PLS) analysis is employed to analyse valid data collected from 235 individuals. The results of this study indicate that telepresence has a higher impact in generating affective-motivational states than the sense of presence. Among the factors, enjoyment shows the highest effect on satisfaction with the 360° virtual tour experience and stress reduction; involvement moderates the effect of telepresence on satisfaction with the 360° virtual tour experience. This study also contributes to virtual reality research by distinguishing the concepts of 'sense of presence' and 'telepresence' as well as demonstrating the mechanisms whereby virtual reality technology influences people's psychological well-being. Timely recommendations are provided for people in order to reduce psychological stress during and after COVID-19 pandemic.

11.
BMC Genomics ; 21(1): 81, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992199

RESUMO

BACKGROUND: Zanthoxylum armatum (Z. armatum) is a highly economically important tree that presents a special numbing taste. However, the underlying regulatory mechanism of the numbing taste remains poorly understood. Thus, the elucidation of the key genes associated with numbing taste biosynthesis pathways is critical for providing genetic information on Z. armatumand the breeding of high-quality germplasms of this species. RESULTS: Here, de novo transcriptome assembly was performed for the five major organs of Z. armatum, including the roots, stems, leaf buds, mature leaves and fruits. A total of 111,318 unigenes were generated with an average length of 1014 bp. Additionally, a large number of SSRs were obtained to improve our understanding of the phylogeny and genetics of Z. armatum. The organ-specific unigenes of the five major samples were screened and annotated via GO and KEGG enrichment analysis. A total of 53 and 34 unigenes that were exclusively upregulated in fruit samples were identified as candidate unigenes for terpenoid biosynthesis or fatty acid biosynthesis, elongation and degradation pathways, respectively. Moreover, 40 days after fertilization (Fr4 stage) could be an important period for the accumulation of terpenoid compounds during the fruit development and maturation of Z. armatum. The Fr4 stage could be a key point at which the first few steps of the fatty acid biosynthesis process are promoted, and the catalysis of subsequent reactions could be significantly induced at 62 days after fertilization (Fr6 stage). CONCLUSIONS: The present study realized de novo transcriptome assembly for the five major organs of Z. armatum. To the best of our knowledge, this study provides the first comprehensive analysis revealing the genes underlying the special numbing taste of Z. armatum. The assembled transcriptome profiles expand the available genetic information on this species and will contribute to gene functional studies, which will aid in the engineering of high-quality cultivars of Z. armatum.


Assuntos
Ácidos Graxos/metabolismo , Regulação da Expressão Gênica de Plantas , Metabolismo dos Lipídeos , Terpenos/metabolismo , Transcriptoma , Zanthoxylum/genética , Zanthoxylum/metabolismo , Vias Biossintéticas , Biologia Computacional/métodos , Repetições de Microssatélites , Anotação de Sequência Molecular , Especificidade de Órgãos
12.
Anal Chem ; 92(2): 1811-1817, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31804064

RESUMO

Herein a rigid three-dimensional (3D) DNA "nanosafe-box" (DNB) for encapsulation and release of a recognition probe (N3) is designed to construct an electrochemical biosensor with the use of electroactive two-dimensional metal-organic framework (2D MOF) nanosheets as signal tags for ultrasensitive detection of mercury ion (Hg2+). Initially, N3 is locked in the 3D cavity of DNB by blocker DNA. After addition of target Hg2+, exonuclease III (Exo-III) digestion is initiated to the liberate DNA "key" (K); thereby, the free K triggers a strand displacement reaction for exposing the prelocked N3 to successfully ligate dibenzocyclooctyne (DBCO)-tagged anchor via metal-catalyst-free click chemistry, in which amounts of 2D MOF nanosheets containing Co(II) as electron mediator are introduced accompanied by significant electrochemical response. Compared with traditional linear or stem-loop DNA nanostructure, the well-designed 3D DNB possesses remarkably enhanced mechanical rigidity and structural stability, resulting in improved accessibility of probes and increased loading amounts of signal tags. More importantly, by this way of encapsulation and release of recognition probes, the background signal is decreased dramatically, leading to increased sensitivity of the proposed biosensor. Consequently, this electrochemical biosensor exhibits outstanding analytical performance for Hg2+ detection with a low detection limit of 33 fM and dynamic linear range of 0.1 pM to 10 nM. This strategy offers an ingenious method for detection of metal ions and biomarkers, possessing potential applications in environmental tests and clinical diagnosis.


Assuntos
Azidas/química , Técnicas Biossensoriais/métodos , Sondas de DNA/química , DNA/química , Técnicas Eletroquímicas/métodos , Mercúrio/análise , Ciclo-Octanos/química , Exodesoxirribonucleases/química , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Conformação de Ácido Nucleico , Reprodutibilidade dos Testes
13.
Eur Radiol ; 30(5): 2973-2983, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31965257

RESUMO

OBJECTIVES: To propose a transfer learning (TL) radiomics model that efficiently combines the information from gray scale and elastogram ultrasound images for accurate liver fibrosis grading. METHODS: Totally 466 patients undergoing partial hepatectomy were enrolled, including 401 with chronic hepatitis B and 65 without fibrosis pathologically. All patients received elastography and got liver stiffness measurement (LSM) 2-3 days before surgery. We proposed a deep convolutional neural network by TL to analyze images of gray scale modality (GM) and elastogram modality (EM). The TL process was used for liver fibrosis classification by Inception-V3 network which pretrained on ImageNet. The diagnostic performance of TL and non-TL was compared. The value of single modalities, including GM and EM alone, and multimodalities, including GM + LSM and GM + EM, was evaluated and compared with that of LSM and serological indexes. Receiver operating characteristic curve analysis was performed to calculate the optimal area under the curve (AUC) for classifying fibrosis of S4, ≥ S3, and ≥ S2. RESULTS: TL in GM and EM demonstrated higher diagnostic accuracy than non-TL, with significantly higher AUCs (all p < .01). Single-modal GM and EM both performed better than LSM and serum indexes (all p < .001). Multimodal GM + EM was the most accurate prediction model (AUCs are 0.950, 0.932, and 0.930 for classifying S4, ≥ S3, and ≥ S2, respectively) compared with GM + LSM, GM and EM alone, LSM, and biomarkers (all p < .05). CONCLUSIONS: Liver fibrosis can be staged by a transfer learning modal based on the combination of gray scale and elastogram ultrasound images, with excellent performance. KEY POINTS: • Transfer learning consists in applying to a specific deep learning algorithm that pretrained on another relevant problem, expected to reduce the risk of overfitting due to insufficient medical images. • Liver fibrosis can be staged by transfer learning radiomics with excellent performance. • The most accurate prediction model of transfer learning by Inception-V3 network is the combination of gray scale and elastogram ultrasound images.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Aprendizado de Máquina , Adulto , Idoso , Algoritmos , Área Sob a Curva , Biomarcadores , Confiabilidade dos Dados , Feminino , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Curva ROC , Estudos Retrospectivos
14.
J Org Chem ; 85(15): 10271-10282, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32664730

RESUMO

Herein, we describe a method for the synthesis of aryl-(het)aryl ketones by Rh(III)-catalyzed direct coupling between quinoline-8-carbaldehydes and (het)arylboronic acids. The method has a broad substrate scope, a high functional group tolerance, and uses commercially available starting materials. Scale-up of the reaction and subsequent synthesis of tubulin polymerization inhibitor demonstrated its utilities. A plausible mechanism was proposed on the basis of the fact that a stable cycloacylrhodium intermediate complex could be used as catalyst, and the complex reacted stoichiometrically with (het)arylboronic acids.


Assuntos
Quinolinas , Ródio , Ácidos Borônicos , Catálise , Cetonas
15.
Molecules ; 25(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098438

RESUMO

Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure-activity relationships were found and are discussed herein by theoretical calculation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Sesquiterpenos/farmacologia , Tetralonas/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Neoplasias/patologia , Sesquiterpenos/síntese química , Sesquiterpenos/química , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , Tetralonas/síntese química , Tetralonas/química , Triazóis/síntese química , Triazóis/química
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 804-811, 2020 Jul 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-32879084

RESUMO

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease that affects adults and children. The most common subtype is psoriasis vulgaris. This article analyzes the characteristics and clinical features of children with psoriasis vulgaris to strengthen the understanding, treatment, and management for children with psoriasis. METHODS: A total of 208 children with psoriasis vulgaris, who were first admitted to the Department of Dermatology, Xiangya Hospital, Central South University from October 2012 to December 2018, were retrospectively analyzed. Their clinical characteristics, results of laboratory examination, treatment options and efficacy were summarized. RESULTS: The age of the 208 children with psoriasis vulgaris was (11.19±3.97) years old, the peak incidence was 12 years old, the disease duration was (27.46±31.30) months, and the male-female ratio was 1∶0.96. The most common site of the first attack was the scalp (37.98%), followed by the trunk (26.44%) and the limbs (22.12%). The causes leading to exacerbation were more common in infections and diets. There were 33 patients (15.87%) with a family history of psoriasis, showing the higher score of Psoriasis Area and Severity Index (PASI) and the higher Dermatological Quality of Life Index (DLQI) (both P<0.05). In all patients, 29 cases (13.94%) were overweight, 19 cases (9.14%) were obese, and the rate of overweight and obesity in children with psoriasis vulgaris was higher than that of normal children in China. In the laboratory test, the serum levels of 25-hydroxyvitamin D (25-OH-VD) were decreased in most patients (47.5%), and the serum 25-OH-VD levels were found to be moderately negatively correlated with PASI score (P<0.05). The score of DLQI in the patient was 5.56±3.57, the score of PASI was 7.25±6.83, and they were positively correlated (r=0.409, P<0.001). In most patients (72.11%), the severity of the disease was mild to moderate. Their treatment was often dominated by topical drugs and Chinese patent medicine (65.67%). Retinoids showed a good effect on children. Cyclosporine and methotrexate were effective in more severe cases. CONCLUSIONS: Children with psoriasis vulgaris are mainly caused by infection and diet. Patients with family history have more serious illness, lower quality of life, and are more likely to have metabolic abnormalities such as overweight and obesity. The serum 25-OH-VD levels in children with psoriasis vulgaris are negatively correlated with the score of PASI.


Assuntos
Obesidade Infantil , Psoríase/epidemiologia , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Catheter Cardiovasc Interv ; 93(S1): 839-845, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30773796

RESUMO

OBJECTIVE: To evaluate efficacy, safety and feasibility of targeted intracoronary injection using pro-urokinase combined with anisodamine (TCA) versus thrombus aspiration (TA) in ST-elevation myocardial infarction (STEMI) patients with high thrombus loads. BACKGROUND: The best method of avoiding thrombus detachment and stroke in PCI patients with high thrombus loads has not yet been established. METHODS: STEMI patients receiving coronary artery angiography or percutaneous coronary intervention (CAG/PCI) with thrombus grade ≥ 3 from January 1, 2017 to June 30, 2018 were randomly assigned to targeted intracoronary thrombolysis (pro-urokinase and anisodamine via catheter (TCA) group), or the TA group which followed the standard thrombus aspiration procedure. Parameters compared included thrombus grade, index of microcirculatory resistance (IMR), postoperative myocardial SPECT, thrombosis in myocardial infarction (TIMI) scores including flow grade, corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grade (TMPG). Adverse events were followed up within 3 months. RESULTS: Thirty-nine patients were finally enrolled. In primary CAG/PCI, the TCA group had higher percentages of TIMI 3 flow and lower IMR values compared with the TA group. The ratio of TMPG 3 grade in the TCA group was higher in repeat CAG, and the perfusion descending area (PDA) presented by SPECT was lower than in the TA group. No significant difference was seen in major adverse coronary events (MACEs) or bleeding events at follow-up. CONCLUSIONS: TCA appears to be effective, safe, and feasible for repatency and reduction of high thrombus burden in primary PCI and may protect myocardial microcirculation with improved outcomes.


Assuntos
Circulação Coronária/efeitos dos fármacos , Trombose Coronária/terapia , Fibrinolíticos/administração & dosagem , Microcirculação/efeitos dos fármacos , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Alcaloides de Solanáceas/administração & dosagem , Trombectomia , Terapia Trombolítica , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Idoso , Cateterismo Cardíaco , China , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/mortalidade , Trombose Coronária/fisiopatologia , Estudos de Viabilidade , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Alcaloides de Solanáceas/efeitos adversos , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversos , Grau de Desobstrução Vascular/efeitos dos fármacos
18.
J Org Chem ; 84(17): 10690-10700, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31419383

RESUMO

A computational mechanistic study has been performed on Pd(II)-catalyzed enantioselective reactions involving acetyl-protected aminomethyl oxazolines (APAO) ligands that significantly improved reactivity and selectivity in C(sp3)-H borylation. The results support a mechanism including initiation of C(sp3)-H bond activation generating a five-membered palladacycle and ligand exchange, followed by HPO42--promoted transmetalation. These resulting Pd(II) complexes further undergo sequential reductive elimination by coordination of APAO ligands and protonation to afford the enantiomeric products and deliver Pd(0) complexes, which will then proceed by oxidation and deprotonation to regenerate the catalyst. The C(sp3)-H activation is found to be the rate- and enantioselectivity-determining step, in which the APAO ligand acts as the proton acceptor to form the two enantioselectivity models. The results demonstrate that the diverse APAO ligands control the enantioselectivity by differentiating the distortion and interaction between the major and minor pathways.

19.
Fish Shellfish Immunol ; 87: 184-192, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30641185

RESUMO

The liver-expressed antimicrobial peptide 2 (LEAP-2) plays a vital role in host immunity against pathogenic organisms. In the present study, cDNA of the LEAP-2 gene was cloned and sequenced from the barbel steed (Hemibarbus labeo). The predicted amino acid sequence of the barbel steed LEAP-2 comprises a signal peptide and a prodomain, which is followed by the mature peptide. Sequence analysis revealed that barbel steed LEAP-2 belongs to the fish LEAP-2A cluster and that it is closely related to zebrafish LEAP-2A. We found that barbel steed LEAP-2 transcripts were expressed in a wide range of tissues, with the highest mRNA levels detected in the liver. In response to lipopolysaccharide (LPS) treatment, LEAP-2 was significantly upregulated in the liver, head kidney, spleen, gill, and mid intestine. A chemically synthesized LEAP-2 mature peptide exhibited selective antimicrobial activity against several bacteria in vitro. Moreover, LEAP-2, alone or in combination with LPS or phorbol 12-myristate 13-acetate, strongly induced a pro-inflammatory reaction in barbel steed monocytes/macrophages (MO/MФ), involving the induction of iNOS activity, respiratory burst, and the pro-inflammatory cytokines IFN-γ, TNF-α, and IL-1ß. Collectively, the results of this study indicate the importance of fish LEAP-2 in the M1-type polarization of MO/MΦ.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Hepcidinas/genética , Hepcidinas/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Bactérias/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Hepcidinas/química , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Monócitos/metabolismo , Filogenia , Alinhamento de Sequência/veterinária
20.
Anal Chem ; 90(15): 9538-9544, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29984573

RESUMO

In this work, on the basis of a new 2D DNA nanoprobe (DNP) and an enzyme-free-target-recycling amplification, an electrochemical biosensor is developed for the ultrasensitive detection of microRNA-21 (miRNA-21). Herein, two ferrocene-labeled bipedal DNPs, which show small steric hindrance and strong stability, are prepared on the basis of the mechanism of the proximity-ligation assay (PLA), improving the space utilization. In the presence of the target, miRNA-21, and a hairpin DNA strand, the DNP will collapse, and then two ferrocene-labeled DNA strands and the miRNA-21 will be simultaneously released from the electrode surface through toehold-mediated strand-displacement reactions (TSDRs), leading to a decrease in the electrochemical signal and realization of enzyme-free target recycling. As a result, the one input target, miRNA-21, could release 2 N ferrocene-labeled DNA strands, achieving a dramatic decrease in the electrochemical signal. Combining DNPs and enzyme-free target recycling, this proposed biosensor showed a linear dependence with miRNA-21 concentration, ranging from 1.0 fM to 10 nM with a detection limit of 0.31 fM. In addition, it is worth mentioning that this biosensor can be regenerated through incubating with three assistant-DNA strands, realizing the reuse of raw materials. Surprisingly, the elaborated biosensor provides a novel strategy for building controllable DNA nanoprobes for the sensitive detection of various biomarkers.


Assuntos
Técnicas Biossensoriais/métodos , Sondas de DNA/química , Compostos Ferrosos/química , Metalocenos/química , MicroRNAs/análise , Técnicas de Amplificação de Ácido Nucleico/métodos , Sequência de Bases , Técnicas Eletroquímicas/métodos , Células HeLa , Humanos , Limite de Detecção , Células MCF-7
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