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1.
Cancer Immunol Immunother ; 73(7): 120, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713243

RESUMO

PURPOSE: The optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC. MATERIALS AND METHODS: We conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding. RESULTS: A total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025). CONCLUSION: Following neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Terapia Neoadjuvante , Estadiamento de Neoplasias , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Idoso , Imunoterapia/métodos , Adulto , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Adv Sci (Weinh) ; 9(30): e2203712, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36050878

RESUMO

Metal-organic frameworks (MOFs) are recognized as promising electrocatalysts for the oxygen evolution reaction (OER) because of their permanent porosity and rich architectural diversity; however, ionic MOFs enabling fast ions exchange during OER are rarely explored. Here, an ionic MOF (Ni-btz) constructed with an azolate ligand is selected, and continuous 3D bimetallic MOF (NiFe-btz) films deriving from high-degree intergrowth of microsized MOFs particles are fabricated. The as-prepared NiFe-btz/NF-OH electrode exhibits excellent OER performance with a low overpotential of 239 mV at 10 mA cm-2 under alkaline condition. The OER charge transfer process and bimetallic coupling effect in ionic NiFe-btz are probed by density functional theory calculations and confirmed via X-ray photoelectron spectroscopy and in situ Raman measurements. The partial density of states of NiFe-btz indicates that the main contribution for electron density around the Fermi level is from Cl ions clarifying the profitable impact of ionic MOF framework. This work systematically demonstrates the relationship of electronic structure and OER activity in ionic, bimetallic MOFs and expands the scope of 3D MOF films for efficient OER.

3.
Ann Palliat Med ; 11(6): 1865-1875, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35272471

RESUMO

BACKGROUND: Sleep disturbance is well documented as a crucial element that impairs health. Depression and health-related quality of life (HRQOL), which on behalf of a patient's overall perception of emotional, physical and social well-being, are increasingly emphasized self-reported health outcomes especially during the coronavirus disease 2019 (COVID-19) pandemic. Among dialysis patients, sleep disturbance is associated with depression and poorer HRQOL. The study was designed to depict the prevalence of sleep disturbance, and to explore the association among sleep, depression, and HRQOL in patients with non-dialysis chronic kidney disease (CKD) during the COVID-19 pandemic. METHODS: A total of 172 non-dialysis CKD patients enrolled in this cross-sectional study, with sociodemographic and clinical data recorded. Sleep, HRQOL, and depression were evaluated via the Pittsburgh Sleep Quality Index (PSQI), the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36), and the 9-item Patient Health Questionnaire (PHQ-9), respectively. RESULTS: A total of 100 (58%) met the criteria for poor sleep. Good sleepers had strikingly disparate HRQOL and depression scores compared to poor sleepers. Sleep disorders were significantly associated with decreased HRQOL and increased depression in regression models adjusted or unadjusted for sociodemographic and clinical characteristics. Mediation analysis indicated depression was a significant mediator explaining 51% of the relationship between sleep status with physical component summary (PCS) and played a fully mediating role in the association between sleep and mental component summary (MCS). CONCLUSIONS: Our study suggested the high incidence of sleep disorders in patients with non-dialysis CKD during the COVID-19 pandemic, as well as the tight associations among sleep, depression, and HRQOL. Considering the negative influences of sleep and depression on HRQOL, appropriate screening and treatment for these treatable health-related domains are necessary for patients with non-dialysis CKD.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Transtornos do Sono-Vigília , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Humanos , Pandemias , Qualidade de Vida/psicologia , Insuficiência Renal Crônica/epidemiologia , Sono , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia
4.
Medicine (Baltimore) ; 101(2): e28325, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029176

RESUMO

ABSTRACT: To study the correlation between calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA), and analyze the diagnostic value of calcaneal QUS in the evaluation of middle-aged and elderly osteoporosis.We assessed bone mineral density (BMD) at the femoral neck and intertrochanteric of left hip and lumbar spine (L1-L4) sites with DXA and QUS parameters of the right and left calcanei in a cohort of 82 patients over the age of 50 years. Using DXA parameters as the gold standard for the diagnosis of osteoporosis, the correlation coefficient between BMD and QUS parameters was calculated. Receiver operating characteristic curve was generated and areas under the curves were evaluated. Cut-off values for QUS were defined.In men, there was a moderate correlation between calcaneal QUS and proximal femoral BMD (P < .05), but no significant correlation between calcaneal QUS and lumbar BMD (P > .05). In women, calcaneal QUS were moderately correlated with lumbar spine and proximal femoral BMD (P < .05). Using DXA as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of calcaneal QUS in the diagnosis of osteoporosis were 90.2%, 89.2%, 100%, 100%, and 50.0%, respectively. According to the receiver operating characteristic curve, when the QUS T-score of calcaneum was -1.8, the area under the curve was 0.888, the sensitivity was 73.21%, and the specificity was 92.31% (P < .05). When the QUS T-score of calcaneum was -2.35, the sensitivity was 37.2% and the specificity was 100%.Calcaneal QUS can be used to predict proximal femoral BMD in middle-aged and elderly people, as well as lumbar BMD in women. As a screening method for osteoporosis, calcaneal QUS has good specificity, so it can be recommended to use it as a pre-screening tool to reduce the number of DXA screening. When the QUS T-score of calcaneum is -1.8, it has the greatest diagnostic efficiency for osteoporosis; when the QUS T-score of calcaneum is ≤-2.35, it can be diagnosed as osteoporosis.


Assuntos
Calcâneo , Osteoporose , Absorciometria de Fóton , Idoso , Densidade Óssea , Calcâneo/diagnóstico por imagem , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Sensibilidade e Especificidade , Ultrassonografia
5.
Arch Med Res ; 53(1): 93-99, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34373133

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been identified in multiple cancers. Recently, NEAT1 is found to be up regulated in cervical cancer. Since the relationship between NEAT1 and thoracic aortic aneurysm (TAA) has not been clarified, our study focused on the role of NEAT1 in TAA. METHODS: Bioinformatics, RNA pulls down and luciferase reporter assay were used to discover and determine miR-324-5p to be a target of NEAT1. RT-qPCR was used to examine NEAT1, RAN and miR-324-5p expression. RESULTS: NEAT1 was up-regulated in TAA patients, as well as HAoSMC and HA-VSMC cells. Down-regulation of NEAT1 could inhibit the proliferative abilities while promoting apoptosis of TAA cells. MiR-324-5p expression was down-regulated in both TAA tissues and cells. Then, RAN was selected out as a target of miR-324-5p. More interestingly, miR-324-5p had inhibitory effects on malignant behaviors of TAA cells. RAN was negatively related with miR-324-5p while positively correlated with NEAT1 in the tissues. Finally, the data of rescue assays manifested that RAN up-regulation could countervail the influence of down-regulation of NEAT1 on TAA cells. CONCLUSION: NEAT1 could contribute to the malignant behaviors of TAA cells by targeting miR-324-5p/RAN. NEAT1 might be an underlying target for the therapy of TAA.


Assuntos
Aneurisma da Aorta Torácica , MicroRNAs , RNA Longo não Codificante , Aneurisma da Aorta Torácica/genética , Proliferação de Células/genética , Regulação para Baixo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína ran de Ligação ao GTP
6.
Front Genet ; 12: 651348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759950

RESUMO

Seven guanylate-binding proteins (GBPs, GBP1-7), identified as a subfamily of interferon-γ-induced guanosine triphosphate hydrolases (GTPases), has been reported to be closely associated with tumor progression, metastasis, and prognosis of cancer patients in recent years. However, the expression patterns, prognostic value, immune infiltration relevance, and biological functions of GBPs in lower-grade glioma (LGG) remain elusive. In this study, by analysis and verification through multiple public data platforms, we found that GBP1, 2, 3, 4 were significantly upregulated in LGG tissues vs normal brain tissue. Analysis based on the Cox proportional hazard ratio and Kaplan-Meier plots demonstrated that the high expressions of GBP 1, 2, 3, 4 were significantly correlated with the poor prognosis of LGG patients. Correlation analysis of clinical parameters of LGG patients indicated that the expressions of GBP 1, 2, 3, 4 were significantly associated with the histological subtype and tumor histological grade of LGG. Furthermore, the correlation analysis of immune infiltration showed that the expressions of GBP1, 2, 3, 4 were significantly and positively correlated with the level of tumor immune-infiltrating cells. In particular, GBP1, 2, 3, 4 expressions were strongly correlated with the infiltration levels of monocyte, TAM, and M1/M2 macrophage, revealing their potential to regulate the polarity of macrophages. Finally, we used the GSEA method to explore the signaling pathways potentially regulated by GBP1, 2, 3, 4 and found that they were all closely associated with immune-related signaling pathways. Collectively, these findings suggested that GBP1, 2, 3, 4 were potent biomarkers to determine the prognosis and immune cell infiltration of LGG patients.

7.
PeerJ ; 9: e10934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717690

RESUMO

Ovate family proteins (OFPs) are a class of proteins with a conserved OVATE domain that contains approximately 70 amino acid residues. OFP proteins are plant-specific transcription factors that participate in regulating plant growth and development and are widely distributed in many plants. Little is known about OFPs in Brassica rapa to date. We identified 29 OFP genes in Brassica rapa and found that they were unevenly distributed on 10 chromosomes. Intron gain events may have occurred during the structural evolution of BraOFP paralogues. Syntenic analysis verified Brassica genome triplication, and whole genome duplication likely contributed to the expansion of the OFP gene family. All BraOFP genes had light responsive- and phytohormone-related cis-acting elements. Expression analysis from RNA-Seq data indicated that there were obvious changes in the expression levels of six OFP genes in the Brassica rapa hybrid, which may contribute to the formation of heterosis. Finally, we found that the paralogous genes had different expression patterns among the hybrid and its parents. These results provide the theoretical basis for the further analysis of the biological functions of OFP genes across the Brassica species.

8.
J Integr Med ; 19(2): 111-119, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33589406

RESUMO

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.


Assuntos
Medicamentos de Ervas Chinesas , Glomerulonefrite , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Glomerulonefrite/tratamento farmacológico , Humanos , Medicamentos sem Prescrição , Comprimidos , Resultado do Tratamento
9.
Exp Ther Med ; 21(1): 62, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33365062

RESUMO

The aim of the present study was to explore the safety of apatinib plus S-1 in treating advanced solid tumors after failure of two or more lines of chemotherapy. A total of 33 patients with advanced cancer treated between April 2016 to March 2019 were retrospectively analyzed. Of these, 13 patients had non-small cell lung cancer (NSCLC), 13 patients had SCLC, 4 patients had esophageal cancer and 3 had cervical cancer. All patients were treated with apatinib 250 mg once daily combined with S-1 60 mg/m2 twice daily for 14 days, repeated every 3 weeks. Adverse reactions were observed until aggravation of adverse reactions beyond the tolerable range or disease progression, and the survival rate and clinical benefits were calculated. The results suggested that the incidence rate of adverse effects (grade 3-4) was 45.5% (15/33). The top three severe adverse effects were hypertension (15.2%), thrombocytopenia (12.1%) and proteinuria (9.1%). A total of 2 patients with lung squamous-cell carcinomas died of severe pulmonary hemorrhage. Other adverse reactions were tolerated in the cohort. A total of 10 patients achieved partial response and the objective response rate was 30.3%. Furthermore, 13 patients achieved stable disease and 10 patients had progressive disease, and accordingly, the disease control rate was 72.7%. In conclusion, apatinib plus S-1 for advanced solid tumor patients as palliative treatment have a certain efficacy and was relatively safe but should be used with caution in patients with squamous-cell lung carcinoma and the efficacy and safety requires further assessment.

10.
Ann Transl Med ; 8(20): 1288, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209868

RESUMO

BACKGROUND: This study aimed to determine the extent to which the survival outcomes of patients with N2-III non-small cell lung cancer (NSCLC) following surgery differ by histological subtype. METHODS: Patients with N2-III NSCLC receiving surgery between 2010 to 2016 were included using the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models were used to identify risk factors associated with overall survival (OS) and non-cancer mortality. The Kaplan-Meier method with log-rank tests was used to estimate survival. Propensity score matching (PSM) was used. Statistical significance was defined as P<0.05. Statistical analyses were done with IBM SPSS 23.0. RESULTS: Ultimately, 2,501 patients with stage N2-III NSCLC receiving surgery were included: 1,891 (75.6%) patients had adenocarcinoma (AC), and 610 (24.4%) patients had squamous cell cancer (SCC). The percentages of patients with AC and SCC receiving chemotherapy and postoperative radiotherapy (PORT) were comparable. In multivariate analysis, histology remained a significant predictor for OS and non-cancer mortality after adjusting for other clinical factors (P<0.05). Based on clinical factors, 522 patients with SCC were ultimately matched with 518 patients with AC using PSM. The 5-year OS of SCC patients after matching was much worse than that of AC patients (36.3% vs. 41.5%; P=0.018), and the 5-year non-cancer mortality of SCC patients was much higher than that of AC patients (18.8% vs. 4.8%; P=0.001). CONCLUSIONS: Among patients with stage N2-III NSCLC following surgery, those with SCC had worse OS than those with AC, due to the higher percentage of patients dying from non-cancer causes.

11.
FASEB J ; 34(12): 15837-15848, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33079458

RESUMO

Acute ischemic stroke is one of the leading causes of death in developed countries and the most common cause of disability in adults worldwide. Despite advances in the understanding of stroke pathophysiology, therapeutic options remain limited. In this study, we explored the interaction of Shrm4 and the metabotropic gamma-aminobutyric acid (GABA) receptors (GABAB ) in ischemic stroke. A transient middle cerebral artery occlusion (MCAO) model was induced by filament insertion in Shrm4+/+ and wild-type C57BL/6J mice, followed by reperfusion for up to 7 days. Baclofen was administered was used to activate GABAB in vivo during reperfusion. Neurological deficits, motor and memory functions, and infarct volume were determined in the various mouse groups. Furthermore, we also developed an oxygen-glucose deprivation (OGD) cell model in primary neurons to test Shrm4/GABAB interactions in vitro. Shrm4 was observed to decrease infarct volume and neuronal cell loss in penumbra, and rescue neurological deficits in MCAO mice. Notably, Shrm4 also increased pole climbing speed, reduced foot faults, and increased escape latency in the Morris water maze test, while reducing neuron autophagy through an interaction with GABAB receptors. GABAB activation using baclofen further reduced OGD-induced neuron damage in culture and stroke outcomes of MCAO, relative to Shrm4 alone. Taken together, Shrm4-mediated GABAB activation confers neuroprotection by reducing neuronal autophagy in acute ischemic stroke.


Assuntos
Autofagia/fisiologia , Isquemia Encefálica/metabolismo , Proteínas do Citoesqueleto/metabolismo , AVC Isquêmico/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neuroproteção/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Células Cultivadas , Glucose/metabolismo , Células HEK293 , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Oxigênio/metabolismo
12.
J Cancer Res Clin Oncol ; 146(3): 721-737, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31786739

RESUMO

PROPOSE: Poly (ADP-ribose) polymerase 1 inhibitors were originally investigated as anti-cancer therapeutics with BRCA1/2 genes mutation. Here, we investigate the effectiveness of a novel PARP1 inhibitor fluzoparib, for enhancing the radiation sensitivity of NSCLC cells lacking BRCA1/2 mutation. METHODS: We used MTS assays, western blotting, colony formation assays, immunofluorescence staining, and flow cytometry to evaluate the radiosensitization of NSCLC cells to fluzoparib and explore the underlying mechanisms in vitro. Through BRCA1 and RAD50 genes knockdown, we established dysfunctional homologous recombination (HR) DNA repair pathway models in NSCLC cells. We next investigated the radiosensitization effect of fluzoparib in vivo using human NSCLC xenograft models in mice. The expression of PARP1 and BRCA1 in human NSCLC tumor samples was measured by immunohistochemistry. Furthermore, we sequenced HR-related gene mutations and analyzed their frequencies in advanced NSCLC. RESULTS: In vitro experiments in NSCLC cell lines along with in vivo experiments using an NSCLC xenograft mouse model demonstrated the radiosensitization effect of fluzoparib. The underlying mechanisms involved increased apoptosis, cell-cycle arrest, enhanced irradiation-induced DNA damage, and delayed DNA-damage repair. Immunohistochemical staining showed no correlation between the expression of PARP1 and BRCA1. Moreover, our sequencing results revealed high mutation frequencies for the BRCA1/2, CHEK2, ATR, and RAD50 genes. CONCLUSION: The potential therapeutic value of fluzoparib for increasing the radiation sensitivity of NSCLC is well confirmed. Moreover, our findings of high mutation frequencies among HR genes suggest that PARP1 inhibition may be an effective treatment strategy for advanced non-small cell lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteína BRCA1 , Proteína BRCA2 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Mutação , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Front Microbiol ; 10: 2132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572337

RESUMO

The dissemination of Klebsiella pneumoniae carbapenemases (KPCs) among Gram-negative bacteria is an important threat to global health. However, KPC-producing bacteria from environmental samples are rarely reported. This study aimed to elucidate the underlying resistance mechanisms of three carbapenem-resistant Aeromonas taiwanensis isolates recovered from river sediment samples. Pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) analysis indicated a close evolutionary relationship among A. taiwanensis isolates. S1-PFGE, Southern blot and conjugation assays confirmed the presence of bla KPC- 2 and qnrS2 genes on a non-conjugative plasmid in these isolates. Plasmid analysis further showed that pKPC-1713 is an IncP-6 plasmid with a length of 53,205 bp, which can be transformed into DH5α strain and mediated carbapenems and quinolones resistance. The plasmid backbone of p1713-KPC demonstrated 99% sequence identity to that of IncP-6-type plasmid pKPC-cd17 from Aeromonas spp. and IncP-6-type plasmid: 1 from Citrobacter freundii at 74% coverage. A 14,808 bp insertion sequence was observed between merT gene and hypothetical protein in p1713-KPC, which include the quinolone resistance qnrS2 gene. Emergence of plasmid-borned bla KPC and qnrS2 genes from A. taiwanensis isolates highlights their possible dissemination into the environment. Therefore, potential detection of such plasmids from clinical isolates should be closely monitored.

14.
Respir Res ; 20(1): 230, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647033

RESUMO

BACKGROUND: In mammalian cells, Aurora serine/threonine kinases (Aurora A, B, and C) are expressed in a cell cycle-dependent fashion as key mitotic regulators required for the maintenance of chromosomal stability. Aurora-A (AURKA) has been proven to be an oncogene in a variety of cancers; however, whether its expression relates to patient survival and the association with radiotherapy remains unclear in non-small cell lung cancer (NSCLC). METHODS: Here, we first analyzed AURKA expression in 63 NSCLC tumor samples by immunohistochemistry (IHC) and used an MTS assay to compare cell survival by targeting AURKA with MLN8237 (Alisertib) in H460 and HCC2429 (P53-competent), and H1299 (P53-deficient) cell lines. The radiosensitivity of MLN8237 was further evaluated by clonogenic assay. Finally, we examined the effect of combining radiation and AURKA inhibition in vivo with a xenograft model and explored the potential mechanism. RESULTS: We found that increased AURKA expression correlated with decreased time to progression and overall survival (p = 0.0447 and 0.0096, respectively). AURKA inhibition using 100 nM MLN8237 for 48 h decreases cell growth in a partially P53-dependent manner, and the survival rates of H460, HCC2429, and H1299 cells were 56, 50, and 77%, respectively. In addition, the survival of H1299 cells decreased 27% after ectopic restoration of P53 expression, and the radiotherapy enhancement was also influenced by P53 expression (DER H460 = 1.33; HCC2429 = 1.35; H1299 = 1.02). Furthermore, tumor growth of H460 was delayed significantly in a subcutaneous mouse model exposed to both MLN8237 and radiation. CONCLUSIONS: Taken together, our results confirmed that the expression of AURKA correlated with decreased NSCLC patient survival, and it might be a promising inhibition target when combined with radiotherapy, especially for P53-competent lung cancer cells. Modulation of P53 function could provide a new option for reversing cell resistance to the AURKA inhibitor MLN8237, which deserves further investigation.


Assuntos
Aurora Quinase A/antagonistas & inibidores , Aurora Quinase A/metabolismo , Azepinas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pirimidinas/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Animais , Azepinas/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Camundongos , Camundongos Nus , Pirimidinas/uso terapêutico , Tolerância a Radiação/fisiologia , Estudos Retrospectivos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
16.
Sci Rep ; 9(1): 9458, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263152

RESUMO

Rapid production of doubled haploids (DHs) through isolated microspore culture is an important and promising method for genetic study of alfalfa. To induce embryogenesis in alfalfa, isolated microspores were submitted to abiotic stresses during their initial culture, in order to stimulate them to form embryos and plantlets. 'Baoding' and 'Zhongmu No 1' alfalfa cultivars supported reproducible and reliable proliferation response irrespective of any stress treatment of microspores. The microspore developmental stage for isolated microspore culture was studied and we found that uninucleate microspores were best to initiate culture. Exposure of microspores to appropriate low temperature or heat shock stresses were able to increase the efficiency of embryogenesis. The most effective low-temperature treatment was 4 °C for 24 h and the frequency of plantlets induction was 20.0%. The most effective heat shock treatment was 32 °C for 2 d and the frequency of plantlets induction was 14.17%. The analysis of ploidy level performed by flow cytometer revealed that the majority of 278 regenerated plantlets were haploid (65.83%) or doubled haploid (33.81%). This is the first report of haploid production in alfalfa through isolated microspore culture.

17.
Sci Adv ; 5(6): eaav5813, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31245535

RESUMO

Thermoelectric modules, consisting of multiple pairs of n- and p-type legs, enable converting heat into electricity and vice versa. However, the thermoelectric performance is often asymmetrical, in that one type outperforms the other. In this paper, we identified the relationship between the asymmetrical thermoelectric performance and the weighted mobility ratio, a correlation that can help predict the thermoelectric performance of unreported materials. Here, a reasonably high ZT for the n-type ZrCoBi-based half-Heuslers is first predicted and then experimentally verified. A high peak ZT of ~1 at 973 K can be realized by ZrCo0.9Ni0.1Bi0.85Sb0.15. The measured heat-to-electricity conversion efficiency for the unicouple of ZrCoBi-based materials can be as high as ~10% at the cold-side temperature of ~303 K and at the hot-side temperature of ~983 K. Our work demonstrates that the ZrCoBi-based half-Heuslers are highly promising for the application of mid- and high-temperature thermoelectric power generation.

18.
Nat Commun ; 10(1): 270, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30655512

RESUMO

Discovery of thermoelectric materials has long been realized by the Edisonian trial and error approach. However, recent progress in theoretical calculations, including the ability to predict structures of unknown phases along with their thermodynamic stability and functional properties, has enabled the so-called inverse design approach. Compared to the traditional materials discovery, the inverse design approach has the potential to substantially reduce the experimental efforts needed to identify promising compounds with target functionalities. By adopting this approach, here we have discovered several unreported half-Heusler compounds. Among them, the p-type TaFeSb-based half-Heusler demonstrates a record high ZT of ~1.52 at 973 K. Additionally, an ultrahigh average ZT of ~0.93 between 300 and 973 K is achieved. Such an extraordinary thermoelectric performance is further verified by the heat-to-electricity conversion efficiency measurement and a high efficiency of ~11.4% is obtained. Our work demonstrates that the TaFeSb-based half-Heuslers are highly promising for thermoelectric power generation.

19.
Onco Targets Ther ; 11: 8349-8355, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568457

RESUMO

PURPOSE: Plasma TGF-ß1 protein levels reportedly may predict the treatment outcomes of lung cancer. We hypothesized that in patients with lung cancer treated with radiation therapy (RT), TGF-ß1 levels may correlate with the percentages of CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in peripheral blood. PATIENTS AND METHODS: Eighty-two lung cancer patients satisfied the inclusion criteria. Platelet-poor plasma was obtained before RT, at the second and fourth weeks during RT, and at the end of RT (pre-, during-, and post-RT, respectively). TGF-ß1 was measured via ELISA, while recording the percentages of lymphocyte subsets in peripheral blood. Short-term efficacy was categorized as complete response, partial response, stable disease, or progressive disease. RESULTS: Patients who had significantly lower TGF-ß1 protein levels after RT than pre-RT seemed to have a better short-term effect (P<0.05) than those who had higher TGF-ß1 levels. There was a significant association between the TGF-ß1 levels and percentages of CD4+ T cells, CD8+ T cells, or CD4+/CD8+ T cell ratio during and at the end of RT. Changes in CD3+ T cells, B cells, or natural killer cells were not statistically related to the changes in TGF-ß1 levels. CONCLUSION: Lung cancer patients with TGF-ß1 levels in plasma after RT that are below pre-RT levels may experience better short-term efficacy. The underlying mechanism may be related to the influence of TGF-ß1 on antitumor immunity.

20.
Phys Rev Lett ; 121(18): 187002, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30444378

RESUMO

We present density functional theory and neutron total scattering studies on quasi-one-dimensional superconducting K_{2}Cr_{3}As_{3} revealing a frustrated structural instability. Our first principles calculations find a significant phonon instability, which, under energy minimization, corresponds to a frustrated orthorhombic distortion. In neutron diffraction studies we find large atomic displacement parameters with anomalous temperature dependencies, which result from highly localized orthorhombic distortions of the CrAs sublattice and coupled K displacements. These results suggest a more complex phase diagram than previously assumed for K_{2}Cr_{3}As_{3} with subtle interplays of structure, electron-phonon, and magnetic interactions.

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