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1.
Phytomedicine ; 125: 155351, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232540

RESUMO

BACKGROUND: Autophagy, a cellular process involving lysosomal self-digestion, plays a crucial role in recycling biomolecules and degrading dysfunctional proteins and damaged organelles. However, in non-small cell lung cancer (NSCLC), cancer cells can exploit autophagy to survive metabolic stress and develop resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which reduce treatment efficacies. Currently, most studies have found that late-stage autophagy inhibitors can hinder EGFR-TKIs resistance, while research on early-stage autophagy inhibitors is still limited. PURPOSE: This study investigates the mechanism via which the Xie-Bai-San (XBS) formula enhances NSCLC cell sensitivity to gefitinib, revealing the relationship between XBS-induced cell death and the inhibition of autophagosome formation. METHODS: Cell viability was assessed using CCK-8 and EdU assays, lentivirus transfection was utilized to generate PC9 cells harboring the PIK3CA E545K mutation (referred to as PC9-M), autophagic flux was monitored using mCherry-GFP-LC3 adenovirus. Protein expression and colocalization were observed through immunofluorescence staining. The interaction between Bcl-2 and Beclin-1 in PC9-GR and PC9-M cells was determined via co-immunoprecipitation (Co-IP) assay, cell apoptosis was assessed by flow cytometry and PI staining, and overall survival analysis of lung adenocarcinoma patients was conducted using the TCGA database. In vivo experiments included a patient-derived xenograft (PDX) model with EGFR and PIK3CA mutations and subcutaneous mice xenografts of NSCLC cell lines (PC9 and PC9-GR). In addition, autophagic vesicles in mouse tumor tissues were observed via transmission electron microscopy analysis. RESULTS: XBS effectively inhibits the proliferation of gefitinib-resistant NSCLC cells and induces apoptosis both in vitro and in vivo. Mechanistically, XBS suppresses gefitinib-induced autophagic flux by inhibiting autophagy through the upregulation of p-mTOR and Bcl-2 and downregulation of Beclin-1. Additionally, XBS enhances the interaction between Bcl-2 and Beclin-1, and the overexpression of Beclin-1 promotes NSCLC cell proliferation and counteracts XBS-induced cell death, while XBS demonstrates minimal impact on autophagosome-lysosome fusion or lysosome function. CONCLUSION: This study reveals a novel role for the XBS formula in impeding autophagy initiation and demonstrates its potential as a candidate drug to counteract autophagy-induced treatment resistance in NSCLC.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Gefitinibe/farmacologia , Proteína Beclina-1 , Neoplasias Pulmonares/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagossomos , Receptores ErbB/metabolismo , Quinazolinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Resistencia a Medicamentos Antineoplásicos , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Linhagem Celular Tumoral
2.
ACS Nano ; 17(18): 17740-17750, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37656667

RESUMO

Site-specific chemical conjugation has long been a challenging endeavor in the field of ligand-directed modification to produce homogeneous conjugates for precision medicine. Here, we develop a chemical amplification-enabled topological modification (Chem-ATM) methodology to establish a versatile platform for the programmable modification of nucleic acid aptamers with designated functionalities. Differing from conventional conjugation strategies, a three-dimensional artificial base is designed in Chem-ATM as a chemical amplifier, giving access to structurally and functionally diversified conjugation of aptamers, with precise control over loading capacity but in a sequence-independent manner. Meanwhile, the sp3 hybridized atom-containing amplifier enables planar-to-stereo conformational transformation of the entire conjugate, eliciting high steric hindrance against enzymatic degradation in complex biological environments. The versatility of Chem-ATM is successfully demonstrated by its delivery of anticancer drugs and imaging agents for enhanced therapy and high-contrast noninvasive tumor imaging in xenograft and orthotopic tumor models. This study offers a different perspective for ligand-directed chemical conjugation to enrich the molecular toolbox for bioimaging and drug development.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Ácidos Nucleicos , Humanos , Medicina de Precisão , Aptâmeros de Nucleotídeos/química , Ácidos Nucleicos/uso terapêutico , Ligantes , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
3.
Opt Express ; 31(18): 29925-29933, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37710781

RESUMO

Based on dual-sideband suppressed-carrier (DSB-SC) modulation and two-stage cascaded four-wave-mixing (FWM), a scheme of broadband dual-chirp frequency-modulated continuous-wave (FMCW) laser source is proposed and experimentally demonstrated. First, via a Mach-Zehnder modulator biased at its null point, an original DSB-SC FMCW signal with 4.0 GHz swept-frequency range and 0.2 GHz/µs sweep rate is generated. Next, the original DSB-SC FMCW signal is sent to a 1 km dispersion compensation fiber for implementing first-stage FWM, a dual-chirp FMCW signal with 12.0 GHz swept-frequency range and 0.6 GHz/µs sweep rate is acquired and used as the pump for second-stage FWM. Finally, via second-stage FWM in a 200 m highly nonlinear fiber, a dual-chirp FMCW signal with a swept-frequency range of 36.0 GHz and sweep rate of 1.8 GHz/µs is generated. Taking the FMCW signal generated at different stages as the emitted signal, we evaluate the ranging resolution through fiber-based distance measurement, and the results demonstrate that the achieved ranging resolutions are 5.31 cm, 2.04 cm, and 1.18 cm, respectively. Through equalizing the optical power of generated FMCW signal over the swept-frequency range, the ranging resolution can be further improved.

4.
BMC Cancer ; 23(1): 732, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553597

RESUMO

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptores ErbB , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinase/genética , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Mutação
5.
Ann Transl Med ; 11(2): 67, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36819571

RESUMO

Background: Growing evidence suggests an association between thyroid stimulating hormone (TSH) and severity of acute ischemic stroke (AIS). However, few studies have ruled out the potential influences of abnormal thyroid hormones when assessing this association. This study aimed to investigate the association between TSH levels and the severity of AIS patients with euthyroidism, and to explore the potential mechanism of TSH on this disease by analyzing the correlation of TSH with lipid profiles. Methods: This retrospective study consisted of 345 patients with normal T3 and T4 levels admitted for first-ever cerebral ischemic stroke. Baseline data of participant were collecte. Laboratory data, including serum levels of TSH and lipid profiles were measured in our hospital's clinical laboratory on admission. Stroke severity was recorded using the National Institutes of Health Stroke Scale (NIHSS). Associations between TSH levels and disease severity were analyzed with logistic regression analysis. Correlations between TSH and lipid profiles were analyzed with Spearman's rank correlation analysis. Results: Among the 345 patients with AIS, the median age was 63 years (63±12 years), 106 patients (30.7%) were female, 237 (68.7%) patients were mild-severity and 108 (31.3%) patients were severity. Data analysis showed that higher serum TSH levels were associated with the mild severity of patients with AIS (P=0.042 in Kruskal-Wallis test, P=0.025 in logistic regression analysis, and P=0.044 in multiple logistic regression), but not in AIS patients with euthyroidism (P=0.078, P=0.337, respectively). Furthermore, TSH levels were correlated with triglycerides (TG) levels not only in total patients (r=0.135, P=0.012) but also in the patients with euthyroidism (r=0.133, P=0.018). Conclusions: TSH levels are associated with the severity of AIS patients, but not in patients with euthyroidism, predicting that stratified management of TSH may be beneficial in patients with AIS. Moreover, TSH levels are correlated with TG levels in patients with AIS.

6.
Pain Med ; 24(4): 382-396, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-35993612

RESUMO

BACKGROUND: Along with increasing research on acupuncture for chronic pain, the validity of sham acupuncture (SA) has also been argued. METHODS: Nine databases were searched for randomized controlled trials (RCTs) from the inception dates of the databases to July 5, 2022. With Markov Chain Monte Carlo methods, a Bayesian multiple-treatment network meta-analysis (NMA) with random-effects model was conducted. RESULTS: A total of 62 RCTs with 6,806 patients and four kinds of treatments (real acupuncture [RA], non-acupuncture [NA], penetrative SA [PSA], and non-penetrative SA [NPSA]) were included. The results indicated that both NPSA and PSA were not superior to NA in improving chronic pain (NPSA: mean difference [MD]= -4.77, 95% confidence interval [CI] -11.09 to 1.52; PSA: MD= -4.96, 95% CI -10.38 to 0.48). After NPSA and PSA were combined into the SA group, the weak trend of pain relief from SA was still not statistically significant (MD= -4.91, 95% CI -9.93 to 0.05). NPSA and PSA had similar effects (MD= 0.18, 95% CI -5.45 to 5.81). RA was significantly associated with pain relief, compared with NPSA and PSA (NPSA: MD= -12.03, 95% CI -16.62 to -7.41; PSA: MD= -11.85, 95% CI -15.48 to -8.23). The results were generally consistent regardless of pain phenotype, frequency, duration, acupuncture methods, analgesic intake, or detection bias. CONCLUSION: These results suggested that acupuncture was significantly associated with reduced chronic pain. The two kinds of placebo acupuncture, NPSA and PSA, have similar effects. Both NPSA and PSA, with a weak but not significant effect, are appropriate to be inert placebo controls in RCTs for chronic pain.

7.
Aging (Albany NY) ; 14(21): 8719-8728, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36260871

RESUMO

BACKGROUND: Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear. METHODS: 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity. RESULTS: Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L, p < 0.001). After Logistic regression analysis, ADA concentrations were negatively correlated with ACI (OR = 1.161, 95% CI: 1.140-1.183, p < 0.001). Smoking and alcohol consumption decreased serum ADA concentrations in patients with ACI, whereas diabetes and hypertension had the opposite effect. CONCLUSIONS: Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Adenosina Desaminase/análise , Estudos Retrospectivos , Estudos de Casos e Controles , Adenosina , Infarto Cerebral
8.
Biomark Res ; 10(1): 73, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36207749

RESUMO

Gastrointestinal cancers (GICs) occupy more than 30% of the cancer-related incidence and mortality around the world. Despite advances in the treatment strategies, the long-term overall survival has not been improved for patients with GICs. Recently, the novel patient-derived organoid (PDO) culture technology has become a powerful tool for GICs in a manner that recapitulates the morphology, pathology, genetic, phenotypic, and behavior traits of the original tumors. Excitingly, a number of evidences suggest that the versatile technology has great potential for personalized treatment, suppling the clinical application of molecularly guided personalized treatment. In the paper, we summarize the literature on the topics of establishing organoid biobanks of PDOs, and their application in the personalized treatment allowing for radiotherapy, chemotherapy, targeted therapy, and immunotherapy selection for GICs. Despite the limitations of current organoid models, high-throughput drug screening of GIC PDO combined with next-generation sequencing technology represents a novel and pivotal preclinical model for precision medicine of tumors and has a great value in promoting the transformation from basic cancer research to clinical application.

9.
Lung Cancer ; 166: 189-196, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35306320

RESUMO

OBJECTIVES: This study aimed to assess the clinical characteristics affecting outcomes after immune checkpoint inhibitors (ICI) therapies in non-small cell lung cancer (NSCLC) patients, and the underlying mechanism in tumor immune micro-environment (TIME). MATERIALS AND METHODS: A total of 144 patients treated with ICI-based strategies were retrospectively analyzed. Expression of 10 immune antibodies in tumor tissues from other 60 untreated NSCLC patients were sequentially tested using multiplexed immunofluorescence (mIF) staining method. Correlation of clinical characteristics with ICI treatment outcomes and TIME characteristics were analyzed. RESULTS: Multivariate logistic and cox regression indicated that BoM negatively affected disease control rate (OR = 0.32, 95%CI: 0.13-0.82, P = 0.018), progression free survival (HR = 3.44, 95% CI:1.97-6.00, P < 0.001) and overall survival (HR = 3.24, 95% CI:1.62-6.50, P = 0.001), irrespective of programmed death-ligand 1 (PD-L1) expression. BoM patients were with significantly lower PD-L1, and this heterogeneity of TIME was then confirmed in the mIF staining, where 36 (61.0%) patients were clustered into immune-subtype A, with low expression of all the detected immune markers, similar to "cold" tumors, and 23 (39.0%) in cluster B with likely "hot" tumors. More patients in immune-subtype A were non-smokers (63.9% vs. 39.1% P = 0.063), with BoM (66.7% vs. 21.7%, P = 0.001), in stage IV(88.9% vs. 65.2%, P = 0.045), and with adenocarcinoma (91.7% vs. 69.6%, P = 0.037). Multivariate logistic regression indicated that BoM was independently associated with the "cold" immune characteristics (OR = 0.19, 95% CI:0.04-0.84, P = 0.028). Combination therapy with chemotherapy /antiangiogenesis or use of bisphosphonate during ICI treatment significantly improved clinical outcomes in BoM patients. CONCLUSIONS: BoM displays adverse impact on clinical outcomes after ICI treatments in NSCLC patients. The "cold" characteristics of TIME may be the underlying mechanism for the attenuated efficacy of ICIs in bone metastatic NSCLC patients.


Assuntos
Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Microambiente Tumoral
11.
Crit Rev Oncol Hematol ; 171: 103610, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35114386

RESUMO

Lung cancer organoids (LCOs) have sprung up in more and more researching fields, because of their ability to recapitulate the three-dimensional structure and functions of the in vivo counterpart organs. However, the culture system for LCOs is still immature, resulting in limited success rate and low tumor purity when culturing LCOs. This is mainly due to the deficiency of an optimal formula of culture medium specially for LCOs. Various cytokines and small molecules have been added in the LCOs culturing system. Compound screening, considering both the mechanism of these molecules and the complexity of lung cancer types is warranted to optimize LCOs culture medium. As methods to culture LCOs increase in sophistication, this model will undoubtedly stand its ground in the coming years in every aspect of cancer researches, especially with major advantages in the field of personalized medicine and tumor microenvironment researches.


Assuntos
Neoplasias Pulmonares , Organoides , Humanos , Neoplasias Pulmonares/patologia , Organoides/patologia , Medicina de Precisão , Microambiente Tumoral
12.
BMC Cancer ; 21(1): 1278, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836510

RESUMO

BACKGROUND: Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. METHODS: We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. RESULTS: A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). CONCLUSION: Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.


Assuntos
Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Antineoplásicos/efeitos adversos , Carbazóis/efeitos adversos , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Lactamas/efeitos adversos , Lactamas/uso terapêutico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metanálise em Rede , Compostos Organofosforados/efeitos adversos , Compostos Organofosforados/uso terapêutico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridazinas/efeitos adversos , Piridazinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-34646330

RESUMO

Patients with EGFR gene mutation often obtain de novo resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or develop secondary resistance to EGFR-TKIs after taking EGFR-TKI therapy. Traditional Chinese medicine (TCM) with different treatment principles, in combination with EGFR-TKIs, plays an important role in the treatment of cancers including resistant non-small cell lung cancer (NSCLC). However, inappropriate use of TCM herbs may induce resistance to gefitinib. Therefore, it is of a great value to evaluate which TCM treatment principle should be combined with EGFR-TKIs, and which one should be avoided, and find out the potential mechanisms. The lentiviral transfection assay was used for overexpression of PIK3CA mutation gene in PC-9 cells to construct PC-9-PIK3CA-mutation (PC-9-PIK3CA-M) cells. Cell proliferation, apoptosis, and the expression of EGFR/PI3K/AKT and EGFR/RAS/RAF/ERK in PC-9-PIK3CA-M and H1975 cells treated by the typical cooling-heat drug, Qing-kai-ling (QKL) and Tan-re-qing (TRQ), or the typical warming-yang drug, Shen-fu (SF) and gefitinib treatment, were detected by MTT, Annexin V/PI double labeling, and Western blot assays, respectively. Tumor xenograft and immunohistochemistry experiments were carried out to confirm the in vitro findings. PC-9-PIK3CA-M cells were less sensitive to gefitinib, when compared with PC-9 cells. QKL injection and TRQ injection, not SF injection, combined with gefitinib induced significantly increased cell growth inhibition and apoptosis in PC-9-PIK3CA-M and H1975 cells. SF injection antagonized the effect of gefitinib in promoting cancer cell apoptosis. QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Similar findings were observed in vivo in H1975 xenograft mouse model. QKL and TRQ, with cooling-heat TCM treatment principle, should be combined with gefitinib in the treatment of NSCLC. Furthermore, warming-yang drug SF should be avoided to be used together with EGFR-TKIs.

14.
Opt Express ; 27(16): 23357-23367, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510614

RESUMO

We investigate the evolution of nonlinear dynamic behaviors of two polarization components (x-PC and y-PC), as well as the interplay of polarization bistability, frequency detuning and injection strength in the vertical cavity surface emitting laser with optical injection. Specifically, by encoding two logic inputs and one clock input in the amplitude of the light from a sampled grating distributed Bragg reflector laser, and by decoding two output logic responses from the x-PC and y-PC emitted by the laser, we demonstrate two parallel data-selection computing. The correct logic output encoded in two emitted PCs response for as short as 100 ps bit time and the response bit time of the correct logic output encoded in the y-PC may be 67 ps by the optimization of the injection strength. The probability of a correct response is controlled by the interplay of the bit time, the injection strength and noise strength, and is equal to 1 in a wide region of the injection strength and noise strength. The chaotic data-selection computing in an optically VCSEL offer interesting perspectives for applications where noise is unavoidable and fast switching is required.

15.
Opt Express ; 27(7): 9857-9867, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31045134

RESUMO

We propose a novel scheme of the real-time ranging for the six orientational targets based on the vertical cavity surface-emitting laser (VCSEL) network with three nodes. In the scheme, we explore a method to realize the globally complete chaotic synchronization (GCCS) of the network with different channel delays. Under the GCCS, we use the six chaotic polarization radars for the ranging of the six orientational targets based on Hilbert transform theory. It is found that the ranging of the six orientational targets has good performance, such as real-time stability and high accuracy, and the absolute errors of the ranging reach millimeter magnitude. Moreover, all relative errors are small and less than 11%.

16.
Opt Express ; 25(18): 21684-21704, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-29041463

RESUMO

According to the principle of complete chaos synchronization and the theory of Hilbert phase transformation, we propose a novel real-time multi-target ranging scheme by using chaotic polarization laser radar in the drive-response vertical-cavity surface-emitting lasers (VCSELs). In the scheme, to ensure each polarization component (PC) of the master VCSEL (MVCSEL) to be synchronized steadily with that of the slave VCSEL, the output x-PC and y-PC from the MVCSEL in the drive system and those in the response system are modulated by the linear electro-optic effect simultaneously. Under this condition, by simulating the influences of some key parameters of the system on the synchronization quality and the relative errors of the two-target ranging, related operating parameters can be optimized. The x-PC and the y-PC, as two chaotic radar sources, are used to implement the real-time ranging for two targets. It is found that the measured distances of the two targets at arbitrary position exhibit strong real-time stability and only slight jitter. Their resolutions are up to millimeters, and their relative errors are very small and less than 2.7%.

17.
Protein Expr Purif ; 128: 86-92, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27546453

RESUMO

Recombinant protein purification remains to be a major challenge in biotechnology and medicine. In this paper we report a simple method for recombinant protein purification using self-assembling peptide-tagged tobacco etch virus protease (TEVp). After construction of an N-terminal ELK16 peptide fusion expression vector, we expressed ELK16-TEVp fusion protein in E. coli. SDS-PAGE analysis showed that ELK16-TEVp was expressed as active protein aggregates which could be purified to 91% purity with 92% recovery by centrifugation in the presence 0.5% Triton X-100. By using His-tagged bovine interferon-γ (His-BoIFN-γ) as the substrate, we demonstrated that EKL16-TEVp had a protease activity of 1.3 × 10(4) units/mg protein with almost 100% cleavage efficiency under the optimized conditions. More importantly, EKL16-TEVp could be removed from the cleavage reaction by single-step centrifugation. After removing the His-tag by nickel-conjugated agarose bead absorption, the recombinant BoIFN-γ (rBoIFN-γ) was purified to 98.3% purity with 63% recovery. The rBoIFN-γ had an antiviral activity of 1.6 × 10(3) units/mg protein against vesicular stomatitis virus. These data suggest that ELK16-TEVp may become a universal tool for recombinant protein purification.


Assuntos
Endopeptidases , Interferon gama/química , Vírus de Plantas/genética , Proteólise , Animais , Bovinos , Endopeptidases/biossíntese , Endopeptidases/química , Endopeptidases/genética , Endopeptidases/isolamento & purificação , Escherichia coli/genética , Escherichia coli/metabolismo , Vírus de Plantas/enzimologia , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(5): 1615-22, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-30001072

RESUMO

Hyperspectral remote sensing data have special advantages, i.e., they have high spectral resolution and strong band continuity, and a great number of spectral information could be widely used in soil properties monitoring research. Using hyperspectral remote sensing technique to analyze saline soil properties makes great significance for the crop growth in the irrigation district and agricultural sustainable development. 221 soil samples were collected from Manasi River Basin to measure soil electrical conductivity (EC), soil organic matter (SOM) and 3 kinds of cation concentrations including Na+, Ca2+ and Mg2+, which were used to obtain sodium adsorption ration value (SAR). The soil hyperspectral curves were also measured. EC, SOM and SAR models were established based on the six spectral-related indices, including raw reflectance (R), standard normal variable (SNV), normalized difference vegetation index (NDVI), logarithm of the reciprocal (LR), the first derivative reflectance (FDR) and continuum-removal reflectance (CR) by the stepwise linear regression method. The results showed that, compared to the other five models, the model of log (EC)~R had the highest accuracy with r value of 0.782 and RMSE value of 0.256. The model of SOM vs. NDVI had the highest accuracy with r value of 0.670 and RMSE value of 5.352. The model of SAR vs. FDR had the highest accuracy with r value of 0.647 and RMSE value of 1.932. As to the model accuracy of the studied soil physico-chemical properties, the log(Ec) model was the most effective one, followed by the SOM model, the SAR model was the most inaccurate. The sensitive wavelengths for EC, SOM and SAR distributed in 395~1 801 nm, 352~1 144 nm and 394~1 011 nm, respectively. Since soil physico-chemical properties were highly spatially variable, there were large differences for the model establishment and validation of the soil properties. This research could be a reference of hyperspectral remote sensing monitoring of salinized soils.

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