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Starting from our previously reported nonnucleoside reverse transcriptase inhibitor (NNRTI, 3), continuous efforts were made to enhance its potency and safety through a structure-based drug design strategy. This led to the discovery of a series of novel piperidine-biphenyl-diarylpyrimidines (DAPYs). Compound 10p, the most active compound in this series, exhibited an EC50 value of 6 nM against wide-type HIV-1 strain, which was approximately 560-fold more potent than the initial compound 3 (EC50 = 3.36 µM). Furthermore, significant improvements were observed in cytotoxicity and selectivity (CC50 > 202.17 µM, SI > 33144) compared to compound 3 (CC50 = 14.84 µM, SI = 4). Additionally, compound 10p demonstrated increased inhibitory activity against clinically mutant virus strains (EC50 = 7-63 nM). Further toxicity evaluation revealed that compound 10p exhibited minimal CYP enzyme and hERG inhibition. Importantly, single-dose acute toxicity testing did not result in any fatalities or noticeable pathological damage in mice. Therefore, compound 10p can be regarded as a lead candidate for guiding further development of biphenyl-diarylpyrimidine NNRTIs with favorable druggability for HIV therapy.
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Fármacos Anti-VIH , Compuestos de Bifenilo , Descubrimiento de Drogas , Transcriptasa Inversa del VIH , VIH-1 , Piperidinas , Pirimidinas , Inhibidores de la Transcriptasa Inversa , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/química , Inhibidores de la Transcriptasa Inversa/síntesis química , Relación Estructura-Actividad , Piperidinas/química , Piperidinas/farmacología , Piperidinas/síntesis química , Humanos , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/química , Animales , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/química , Fármacos Anti-VIH/síntesis química , Ratones , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Transcriptasa Inversa del VIH/metabolismo , Estructura Molecular , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Piperazinas/química , Piperazinas/farmacología , Piperazinas/síntesis química , Piperazina/química , Piperazina/farmacologíaRESUMEN
Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Esofágicas , Neoplasias Hepáticas , Neoplasias Pulmonares , Melanoma , Neoplasias Gástricas , Humanos , Glucosa , Estudios Retrospectivos , Neoplasias Pulmonares/patología , Linfocitos/patología , Neoplasias Hepáticas/patología , Neoplasias Esofágicas/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patologíaRESUMEN
The reasonably constructed high-performance electrocatalyst is crucial to achieve sustainable electrocatalytic water splitting. Alloying is a prospective approach to effectively boost the activity of metal electrocatalysts. However, it is a difficult subject for the controllable synthesis of small alloying nanostructures with high dispersion and robustness, preventing further application of alloy catalysts. Herein, we propose a well-defined molecular template to fabricate a highly dispersed NiRu alloy with ultrasmall size. The catalyst presents superior alkaline hydrogen evolution reaction (HER) performance featuring an overpotential as low as 20.6 ± 0.9 mV at 10 mA·cm-2. Particularly, it can work steadily for long periods of time at industrial-grade current densities of 0.5 and 1.0 A·cm-2 merely demanding low overpotentials of 65.7 ± 2.1 and 127.3 ± 4.3 mV, respectively. Spectral experiments and theoretical calculations revealed that alloying can change the d-band center of both Ni and Ru by remodeling the electron distribution and then optimizing the adsorption of intermediates to decrease the water dissociation energy barrier. Our research not only demonstrates the tremendous potential of molecular templates in architecting highly active ultrafine nanoalloy but also deepens the understanding of water electrolysis mechanism on alloy catalysts.
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BACKGROUND: The albumin-bilirubin (ALBI) score is a novel indicator of liver function. Some studies showed that the ALBI score was a predictive marker for the prognosis and efficacy of drug therapy in malignancies. We aimed to assess the predicted role of ALBI score in the sensitivity to therapy with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). The clinical data of 226 HER2-positive BC patients at the Harbin Medical University Cancer Hospital from January 2017 and December 2018 were retrospectively collected. The ALBI score was calculated with serum albumin and bilirubin before diagnosis. The associations between ALBI score and trastuzumab resistance were analyzed by logistic regression analyses. The patients with trastuzumab resistance had higher ALBI scores compared with the patients without trastuzumab resistance. Moreover, there were weak correlations between the ALBI score and lymph node status (P= 0.093). In addition, multivariate analysis revealed that the ALBI score was an independent prognostic factor for trastuzumab resistance in HER2-positive BC. High ALBI score is associated with trastuzumab resistance in HER2-positive BC. Future studies are needed.
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Neoplasias de la Mama , Neoplasias Hepáticas , Femenino , Humanos , Bilirrubina , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias Hepáticas/patología , Pronóstico , Estudios Retrospectivos , Albúmina Sérica/análisis , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Resistencia a AntineoplásicosRESUMEN
BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer. OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients. METHODS: 517 BC patients were studied retrospectively. Patients' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models. RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05). CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.
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Neoplasias Óseas , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Estudios Retrospectivos , Mama/patología , Pronóstico , Grasa Subcutánea/patologíaRESUMEN
Nanostructured antiferromagnetic (AFM) NiO has attracted much attention from both the fundamental and applied perspectives. Understanding the two-magnon (2 M) is of great significance in NiO applications such as spin valves and next-generation magnetic random access memories (MRAM). We investigated the phonon modes and antiferromagnetically ordered states of NiO nanoparticles prepared by empirically controlled measurements. An intensity enhancement of the 2 M mode was observed by Raman spectroscopy as the NiO nanoparticles were vacuum annealed at 650 â. The increased 2 M peak intensity in NiO nanoparticles is explained by the local symmetry conversions from NiO5 to NiO6 configurations due to the oxygen redistribution during the vacuum annealing. The change of the splitting of anisotropic transverse optical (TO) phonon with different oxygen contents was also revealed by the Raman spectroscopy. We have shown that the changes in the oxygen environment underlie both the change in the 2 M intensity and the splitting of TO phonon in the NiO nanoparticles. Our work offers an efficient avenue to strengthen the AFM ordering and emphasizes the effect of vacuum annealing of the NiO nanoparticles, opening the interesting possibility of individual parameter control in practical applications.
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Following on our initial discovery of S-CN-DABOs as non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel S-N3-DABO derivatives F1-F31 were developed by substituting the cyano group of S-CN-DABOs with azide group. Some of these compounds were conferred significantly increased potency against wild-type HIV-1 and clinically observed mutant strains. Remarkably, the best compound F10 exerted a 7-fold improvement in potency (EC50 = 0.053 µM) and 12.5-fold higher selectivity (SI = 6818) in MT-4 cells infected with wild-type HIV-1, compared to that of the parent compound B1 (EC50 = 370 nM, SI = 547). The anti-HIV-1 activity of F10 against the tested mutant strains was prominently enhanced. For wild-type reverse transcriptase, it was approximately 19-fold more potent (IC50 = 0.080 µM) than B1 (IC50 = 1.51 µM). It was not found that this analog had significant inhibition of hERG, CYP, and acute toxicity after a single dose of F10 (1.0 g/kg).
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Fármacos Anti-VIH , VIH-1 , Inhibidores de la Transcriptasa Inversa/farmacología , Relación Estructura-Actividad , Transcriptasa Inversa del VIH , Pirimidinas/farmacología , Pirimidinonas/farmacología , Compuestos Heterocíclicos con 1 Anillo , VIH-1/metabolismo , Fármacos Anti-VIH/farmacología , Diseño de FármacosRESUMEN
Excessive exposure to light at night (LAN) has become a serious public health concern. However, little is known about the impact of indoor LAN exposure on blood pressure, particularly among young adults. We aimed to investigate the effects of bedroom individual-level LAN exposure in real-world environment on blood pressure and hypertension among vulnerable young adults, and to evaluate the possible buffering effect of physical activity. In this cross-sectional study, a total of 400 healthy young adults aged 16-22 years were included. Bedroom LAN exposure was recorded at 1-min intervals for two consecutive nights using a TES-1339 R illuminance meter. Blood pressure was measured three times (8-11 a.m. in the physical examination day) in the seated position using an Omron HEM-7121 digital sphygmomanometer. A wrist-worn triaxial accelerometer (ActiGraph GT3X-BT) was used to assess physical activity for seven consecutive days. Each 1 lx increase of bedroom LAN intensity was associated with 0.55 mmHg-increase in SBP (95% CI: 0.15, 0.95), 0.30 mmHg-increase in DBP (95% CI: 0.06, 0.54), and 0.38 mmHg-increase in MAP (95% CI: 0.12, 0.65). Higher levels of LAN exposure were associated with increased risk of hypertension (LAN ≥ 3lx vs. LAN < 3lx: OR = 3.30, 95%CI = 1.19-9.19; LAN ≥ 5lx vs. LAN < 5lx: OR = 3.87, 95%CI = 1.37-10.98). However, these detrimental effects of bedroom LAN exposure on blood pressure and hypertension were not observed among young adults with high MVPA (≥2 h/day) level. MVPA can alleviate negative effects of bedroom LAN exposure on blood pressure and hypertension. Maintaining bedroom settings darkness at night may be an important strategy for reducing the risk of hypertension. Furthermore, for individuals living with high levels of indoor LAN exposure, regular physical activity may be a good option for preventing cardiovascular disease and hypertension.
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Ritmo Circadiano , Hipertensión , Presión Sanguínea , China/epidemiología , Ritmo Circadiano/fisiología , Estudios Transversales , Ejercicio Físico , Humanos , Hipertensión/epidemiología , Luz , Contaminación Lumínica , Adulto JovenRESUMEN
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer. HCC and ICC differ in treatment and prognosis, warranting an effective differential diagnosis between them. This study aimed to explore the clinical value of mean platelet volume (MPV) to discriminate between HCC and ICC. MATERIAL/METHODS: We performed a retrospective analysis of ICC and HCC patients who were from the Harbin Medical University Cancer Hospital, China. Logistic regression analysis was used to identify the independent factors for the differentiation of HCC and ICC. A receiver operating characteristic curve was built to evaluate the diagnostic performance of the potential model. An independent validation study was performed to validate the diagnostic ability. RESULTS: ICC patients were detected in 146 out of 348 patients in the primary cohort. MPV levels were decreased in ICC patients compared with those in HCC patients. Logistic regression analysis revealed that MPV was an independent factor in distinguishing HCC from ICC. A combination of sex, hepatitis B surface antigen, MPV, alpha-fetoprotein, and carbohydrate antigen 19-9 demonstrated a good capability to differentiate HCC from ICC. Similar results were achieved in the validation cohort. CONCLUSIONS: MPV may be a new marker to help distinguish ICC from HCC. Further validation studies are required.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patología , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Volúmen Plaquetario Medio , Estudios RetrospectivosRESUMEN
BACKGROUND: In hepatocellular carcinoma (HCC), pulmonary metastasis (PM) after hepatectomy is associated with poor clinical outcomes. The crucial phases of tumour cell proliferation, angiogenesis, and metastasis all entail platelet activation. In HCC, platelet distribution width (PDW) suggests platelet size changes and predicts a worse prognosis. The aim of this study was to assess the association between PDW and PMs in HCC patients receiving hepatectomy. MATERIAL/METHODS: From January 2013 to December 2015, a cohort of patients who underwent hepatectomy for HCC at the Harbin Medical University Cancer Hospital in China were retrospectively evaluated. The relationship between PDW levels and clinical and demographic parameters was examined. To investigate the relationships between predicted factors and PM, a competing risk model was used. From January 2016 to December 2018, a validation cohort of 109 patients from the First Affiliated Hospital of Harbin Medical University was studied independently. RESULTS: In the primary cohort, 19 out of 214 patients had postoperative PMs. In HCC patients with PM, PDW levels were lower than in those without PM. There was a significant difference in the cumulative incidence of 2-year PM between the high-PDW and low-PDW groups after controlling for competing risk events (death prior to the development of PM) (p < 0.001). In addition, PDW was also found to be an independent predictor for PM in a multivariable competing risk analysis. The results were externally validated in another cohort. CONCLUSIONS: In HCC, preoperative PDW is significantly associated with PM. PDW could be a biomarker for post-operative PM in HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Volúmen Plaquetario Medio , Pronóstico , Estudios RetrospectivosRESUMEN
We report two-dimensional correlation spectroscopy (2D-COS) analyses of the Raman spectra of NiO nanoparticles over a temperature range from 100 to 300 K. 2D-Raman correlation spectra suggest strong correlation of the phonon spectral intensity variation with the magnetic ordering in NiO nanoparticles. It is revealed that the antiferromagnetic ordering affects the TO phonon anisotropy in NiO nanoparticles. We elucidate the complex spectral features of two-magnon (2 M) bands by performing appropriate 2D-COS model simulations. Significant spin-phonon coupling in NiO nanoparticles is supported by our results. High energy magnon-magnon interaction tails are also found to be involved in the spin-phonon coupling. 2D-COS analyses provide rich information regarding the nature of the phonon and magnon excitations of NiO nanoparticles.
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Results from recently completed studies suggested that the NH2-naphthyl-diarylpyrimidine JX-7 displayed remarkable inhibitory activity against wild-type HIV-1 (EC50 = 5 nM) and numerous clinically observed variants in MT-4 cells; however, its high cytotoxicity (CC50 = 19 µM) precluded its further development as a clinical candidate. One approach we took to improve the safety involved replacing the naphthyl of JX-7 with biphenyl to provide a series of novel NH2-biphenyl-DAPYs. Investigation of the structure-activity relationships (SARs) led to the identification of 4ab, a potent NNRTI with significantly reduced cytotoxicity (CC50 = 120 µM), approximately 6-fold lower than JX-7, which maintained remarkable anti-HIV-1 activity against wild-type HIV-1 (EC50 = 1.9 nM) and multiple mutant strains simultaneously. Also, 4ab displayed weak CYP sensitivity, little inhibition of hERG, and no apparent in vivo acute toxicity. These promising results demonstrate that 4ab can be used as a drug candidate for HIV-1 therapy.
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Fármacos Anti-VIH , VIH-1 , Fármacos Anti-VIH/toxicidad , Compuestos de Bifenilo , Diseño de Fármacos , Transcriptasa Inversa del VIH , VIH-1/metabolismo , Compuestos Heterocíclicos con 1 Anillo , Pirimidinas/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Relación Estructura-ActividadRESUMEN
Background: Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Sarcopenia is related to adverse clinical outcomes in patients with malignancies. Muscle index is a key parameter in evaluating sarcopenia. However, there is no data investigating the association between muscle index and distant metastasis in breast cancer. The aim of this study was to explore whether muscle index can effectively predict distant metastasis and death outcomes in breast cancer patients. Study Design: The clinical data of 493 breast cancer patients at the Harbin Medical University Cancer Hospital between January 2014 and December 2015 were retrospectively analyzed. Quantitative measurements of pectoralis muscle area and skeletal muscle area were performed at the level of the fourth thoracic vertebra (T4) and the eleventh thoracic vertebra (T11) of the chest computed tomography image, respectively. The pectoralis muscle index (PMI) and skeletal muscle index (SMI) were assessed by the normalized muscle area (area/the square of height). Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. Result: The patients with metastases had lower PMI at T4 level (PMI/T4) and SMI at T11 level (SMI/T11) compared with the patients without metastases. Moreover, there were significant correlations between PMI/T4 and lymphovascular invasion, Ki67 expression, multifocal disease, and molecular subtype. In addition, multivariate analysis revealed that PMI/T4, not SMI/T11, was an independent prognostic factor for distant metastasis-free survival (DMFS) and overall survival (OS) in breast cancer patients. Conclusions: Low PMI/T4 is associated with worse DMFS and OS in breast cancer patients. Future prospective studies are needed.
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Aims. Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), and macrophages play a key role in this process. The aim of this study was to discover the role of IκB kinase α (IKKα) in macrophages in the process of AKI-to-CKD transition. Main Methods. We crossed lyz2-Cre mice with IKKα-floxed mice to generate mice with IKKα ablation in macrophages (Mac IKKα-/-). A mouse renal ischemia/reperfusion injury (IRI) model was induced by clamping the renal artery for 45 minutes. Treated mice were evaluated for blood biochemistry, tissue histopathology, and fibrosis markers. Macrophages were isolated from the peritoneal cavity for coculturing with tubular epithelial cells (TECs) and flow cytometry analysis. Key Findings. We found that fibrosis and kidney function loss after IRI were significantly alleviated in Mac IKKα-/- mice compared with wild-type (WT) mice. The expression of fibrosis markers and the infiltration of M2 macrophages were decreased in the kidneys of Mac IKKα-/- mice after IRI. The in vitro experiment showed that the IRI TECs cocultured with IKKα-/- macrophages (KO MΦs) downregulated the fibrosis markers accompanied by a downregulation of Wnt/ß-catenin signaling. Significance. These data support the hypothesis that IKKα is involved in mediating macrophage polarization and increasing the expression of fibrosis-promoting inflammatory factors in macrophages. Therefore, knockdown of IKKα in macrophages may be a potential method that can be used to alleviate the AKI-to-CKD transition after IRI.
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Quinasa I-kappa B/deficiencia , Túbulos Renales/patología , Macrófagos/inmunología , Daño por Reperfusión/inmunología , Animales , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Células Epiteliales , Fibrosis , Técnicas de Silenciamiento del Gen , Humanos , Quinasa I-kappa B/genética , Túbulos Renales/irrigación sanguínea , Activación de Macrófagos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Transgénicos , Cultivo Primario de Células , Daño por Reperfusión/complicaciones , Daño por Reperfusión/patología , Vía de Señalización Wnt/inmunologíaRESUMEN
Alhagi sparsifolia Shap. is a perennial herbaceous plant belonging to the genus Alhagi, Leguminosae. This species is of high nutritional, medicinal and ecological values. The complete chloroplast genome was 128,418 bp and lost an IR (inverted repeat) region. Further annotation revealed the chloroplast genome contains 108 genes, including 75 protein coding genes, 29 tRNA genes, and 4 rRNA genes. A total of 103 simple sequence repeats (SSRs) were identified in the chloroplast genome. This chloroplast genome resource will be useful for study on the evolution and genetic diversity of A. sparsifolia in the future.
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NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.
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Angelica , Biología Computacional , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Platelets play a key role in tumor progression and metastasis. C-type lectin-like receptor 2 (CLEC-2) is the receptor expressed on platelets and the marker of platelet activation. OBJECTIVE: This study aims to determine whether soluble CLEC-2 levels differ between patients with benign colorectal polyps and those with colorectal cancer (CRC). METHODS: We measured plasma soluble CLEC-2 by enzyme-linked immunosorbent assay in 150 patients with colorectal polyps, 150 CRC patients without metastasis, 150 CRC liver metastasis, and 150 control subjects. RESULTS: The CRC patients had higher soluble CLEC-2 levels than patients with colorectal polyps (p< 0.001). Moreover, CRC patients with liver metastases displayed higher CLEC-2 levels than those in CRC patients without metastases (p< 0.001). In the CRC patients, CLEC-2 levels were correlated with lymph node metastasis and advanced stage. In the patients with polyps, there was a significant difference in CLEC-2 levels among patients with hyperplastic polyp, sessile serrated adenoma, and traditional serrated adenoma (p< 0.001). The ROC curve analysis revealed CLEC-2 had an optimal sensitivity of 77.3% and specificity of 94.6% for the screening of CRC, and sensitivity of 71.0% and specificity of 76.7% for the differential diagnosis of colorectal polyps and CRC. CONCLUSIONS: CRC patients have higher CLEC-2 levels than patients with colorectal polyps and healthy controls. Moreover, there is a significant difference in CLEC-2 levels among polyp subtypes. Further research is warranted.
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Pólipos del Colon/fisiopatología , Neoplasias Colorrectales/fisiopatología , Lectinas Tipo C/metabolismo , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Effects of three compound growth regulators formulated with hypersensitivity protein, spermidine, salicylic acid and DA-6 (diethyl aminoethanol hexanoate) were tested on Xinjiang Jun Jujube. The doses of compound growth regulators were named as A (Hypersensitivity protein + spermidine + salicylic acid at the rate of 30 mg/L, 0.1 mmol/L and 0.25 mmol/L, respectively), B (Hypersensitive protein + spermidine + DA-6 at the rate of 30 mg/L, 0.1 mmol/L and 30 mg/L, respectively) and C (Spermidine + salicylic acid + DA-6 at the rate of 0.1 mmol/L, 0.25 mmol/L and 30 mg/L, respectively) versus a control group CK (contained only water). Fruit anatomical structures were compared after spraying. The results indicated that after spraying, the thickness of the upper and lower epidermal cells and the stratum corneum were increased. However, the upper epidermal stratum corneum became significantly thicker than the lower epidermis. Spraying with A improved the thickness of upper and lower epidermal cells, stratum corneum, the central vein and mesophyll. The cumulative effects of all these changes in leaf and fruit anatomical structures provided the resistance of the experimental fruit plant to stress. While the B and C regulators had inhibitory effects. So, the results obtained after spraying A category were beneficial to improve the stress resistance of the fruits. The length and cell area of pericarp and sarcocarp cells in the treatment groups were not changed significantly. But the length, number of sarcocarp cells and number of gaps were lower than those in the CK. This study can provide new measures for improving plant resistance in jujube production.
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BACKGROUND: The microsatellite instability (MSI) in colorectal cancer (CRC) has a more favorable clinical outcome and is characterized by highly upregulated expression of various immunological checkpoints than microsatellite stable (MSS) tumors. Apoptosis inhibitor of macrophage (AIM) is a circulating protein and circulates throughout the body to remove cellular debris. The aim of this study was to evaluate the association between MSI status and AIM levels in CRC patients. METHODS: In this study, we evaluated the levels of AIM by Enzyme Linked Immuno-Sorbent Assay (ELISA) in serum of 430 CRC patients. All patients' clinical and laboratory characteristics at initial diagnosis were collected. The relationship between AIM levels and MSI status was examined. RESULTS: 64 patients (14.9%) were identified as having MSI-H (high-frequency MSI) and 366 casess (85.1%) having MSS. Patients with an MSI-H phenotype had lower AIM levels compared with MSS patients. Moreover, AIM levels were correlated with histological type and MSI status. Logistic regression analysis revealed that decreased AIM levels were independently associated with MSI-H phenotype after adjusting confounding factors. CONCLUSION: Reduced AIM levels are associated with MSI-H subtyping of CRC. Further research on the involvement of AIM in MSI-H CRC is needed.
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Neoplasias del Colon , Neoplasias Colorrectales , Macrófagos , Inestabilidad de Microsatélites , Apoptosis , Neoplasias Colorrectales/genética , Femenino , Humanos , Masculino , PronósticoRESUMEN
BACKGROUND: Ovarian cancer (OC) is one of the most malignant gynecological cancers. Platelets play a profound role in cancer growth and metastasis. Platelet distribution width (PDW) is an indicator of platelet activation and is altered in malignancies. However, the prognostic value of PDW in OC remains unclear. This present study aimed to investigate the predictive significance of PDW in OC. METHODS: 221 OC patients, between January 2013 and December 2013, were included in this study. The correlations between PDW and clinicopathological features were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. RESULTS: Of the 221 patients, increased PDW levels were observed in 163 (73.6%) patients. Kaplan-Meier analysis revealed that higher PDW levels were associated with poor progression-free survival and overall survival (both p< 0.001). Cox-regression analysis confirmed the independent predictive value of PDW on overall survival (HR = 2.820, 95% CI = 1.776-4.476, p< 0.001). CONCLUSION: Higher PDW levels predict poor prognosis in patients with OC. Elevated PDW may be a novel target for therapy.