RESUMEN
The tribe Collabieae (Epidendroideae, Orchidaceae) comprises approximately 500 species. Generic delimitation within Collabieae are confusing and phylogenetic interrelationships within the Collabieae have not been well resolved. Plastid genomes and nuclear internal transcribed spacer (ITS) sequences were used to estimate the phylogenetic relationships, ancestral ranges, and diversification rates of Collabieae. The results showed that Collabieae was subdivided into nine clades with high support. We proposed to combine Ancistrochilus and Pachystoma into Spathoglottis, merge Collabium and Chrysoglossum into Diglyphosa, and separate Pilophyllum and Hancockia as distinctive genera. The diversification of the nine clades of Collabieae might be associated with the uplift of the Himalayas during the Late Oligocene/Early Miocene. The enhanced East Asian summer monsoon in the Late Miocene may have promoted the rapid diversification of Collabieae at a sustained high diversification rate. The increased size of terrestrial pseudobulbs may be one of the drivers of Collabieae diversification. Our results suggest that the establishment and development of evergreen broadleaved forests facilitated the diversification of Collabieae.
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Orchidaceae , Filogenia , Orchidaceae/genética , Orchidaceae/clasificación , Bosques , Genoma de Plastidios/genética , Filogeografía , ADN Espaciador Ribosómico/genética , Análisis de Secuencia de ADN , Asia , ADN de Plantas/genéticaRESUMEN
Chronic airway inflammation mediated by CD8+ T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+ T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-γ+ CD8+ Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ CD8+ Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ CD8+ Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.
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Diferenciación Celular , Fumar Cigarrillos , Interferón gamma , Interleucinas , Enfisema Pulmonar , Linfocitos T Citotóxicos , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Diferenciación Celular/inmunología , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/inmunología , Modelos Animales de Enfermedad , Inflamación/etiología , Inflamación/inmunología , Interferón gamma/inmunología , Interleucinas/inmunología , Enfisema Pulmonar/etiología , Enfisema Pulmonar/inmunología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Objective: YKL-40, also known as chitinase-3-like-1 (CHI3L1), is a human cartilage glycoprotein-39, with its N-terminus consisting of tyrosine (Y), lysine (K), and leucine (L), hence the name YKL-40. In this study, we explored whether YKL-40 could promote the expression of inflammatory factors in type â ¡ alveolar epithelial cells. Methods: A549 cells were cultured in vitro with interleukin (IL)-1ß (20 ng/mL), IL-6 (20 ng/mL), tumor necrosis factor-alpha (TNF-α) (20 ng/mL), and interferon-gamma (IFN-γ) (20 ng/mL). The expression of YKL-40 transcription was determined by RT-qPCR. A549 cells were cultured with IL-1ß at 5, 10, and 20 ng/mL and the expression of YKL-40 protein was determined by Western blot. A549 cells were cultured with recombinant YKL-40 protein at 0, 100, 500, and 1 000 ng/mL and the expression levels of IL-6 and IL-8 were measured by RT-qPCR. Three pairs of small interfering RNAs targeting YKL-40 (si- YKL-40-1/2/3) and the negative control (NC) were designed and used to transfect A549 cells, respectively, and the expression of YKL-40 was determined by RT-qPCR and Western blot. si- YKL-40-3 was screened out for subsequent experiments. In A549 cells, si- YKL-40-3 and si-NC were transfected and, then, IL-1ß (20 ng/mL) was added in for culturing. The expression of YKL-40, IL-6, and IL-8 was determined by RT-qPCR and the expression of multiple factors in the supernatant was measured with the QAH-INF-1 kit. Results: RT-qPCR results showed that IL-1ß could up-regulate YKL-40 protein transcription level compared with that of the control group and the difference was statistically significant ( P<0.01), but IL-6, TNF-α, and IFN-γ could not up-regulate YKL-40 protein transcription level. Western blot results showed that IL-1ß (20 ng/mL) could significantly promote the expression of YKL-40 and, compared with that of the control group, the differences showed by groups treated with different concentrations of IL-1ß were all statistical significant ( P<0.01). After adding human recombinant YKL-40 protein to A549 cells, the results showed that the expression of inflammatory factors IL-6 and IL-8 was significantly increased and the difference was statistically significant compared with that of the control group ( P<0.05). After the expression of YKL-40 was decreased by si- YKL-40-3 transfection, the expression of IL-6 ( P<0.05), IL-8 ( P<0.05), and other inflammatory factors was inhibited compared with that of the control group. Conclusion: YKL-40 can promote the expression and secretion of IL-6, IL-8, and other acute inflammatory factors in A549 cell line, a type â ¡ alveolar epithelial cell model, thus aggravating the inflammatory response. Targeted inhibition of YKL-40 expression may effectively inhibit inflammatory response.
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Células Epiteliales Alveolares , Factor de Necrosis Tumoral alfa , Humanos , Células Epiteliales Alveolares/metabolismo , Células A549 , Proteína 1 Similar a Quitinasa-3/genética , Proteína 1 Similar a Quitinasa-3/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Interleucina-8 , Interferón gammaRESUMEN
BACKGROUND: The application of clinical mNGS for diagnosing respiratory infections improves etiology diagnosis, however at the same time, it brings new challenges as an unbiased sequencing method informing all identified microbiomes in the specimen. METHODS: Strategy evaluation and metagenomic analysis were performed for the mNGS data generated between March 2017 and October 2019. Diagnostic strengths of four specimen types were assessed to pinpoint the more appropriate type for mNGS diagnosis of respiratory infections. Microbiome complexity was revealed between patient cohorts and infection types. A bioinformatic pipeline resembling diagnosis results was built based upon multiple bioinformatic parameters. RESULTS: The positive predictive values (PPVs) for mNGS diagnosing of non-mycobacterium, Nontuberculous Mycobacteria (NTM), and Aspergillus were obviously higher in bronchoalveolar lavage fluid (BALF) demonstrating the potency of BALF in mNGS diagnosis. Lung tissues and sputum were acceptable for diagnosis of the Mycobacterium tuberculosis (MTB) infections. Interestingly, significant taxonomy differences were identified in sufficient BALF specimens, and unique bacteriome and virome compositions were found in the BALF specimens of tumor patients. Our pipeline showed comparative diagnostic strength with the clinical microbiological diagnosis. CONCLUSIONS: To achieve reliable mNGS diagnosis result, BALF specimens for suspicious common infections, and lung tissues and sputum for doubtful MTB infections are recommended to avoid the false results given by the complexed respiratory microbiomes. Our developed bioinformatic pipeline successful helps mNGS data interpretation and reduces manual corrections for etiology diagnosis.
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Microbiota , Mycobacterium tuberculosis , Infecciones del Sistema Respiratorio , Humanos , Metagenómica/métodos , Microbiota/genética , Líquido del Lavado Bronquioalveolar/microbiología , Infecciones del Sistema Respiratorio/diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The continuous activation of transcription factors drives many diseases, including tumors, autoimmune disease, neurodegenerative disease, and male infertility. Thus, Blocking the transcriptional activity of these proteins may inhibit disease progression. In this study, we developed a new method to specifically inhibit the activity of the transcription factor STAT3. METHODS: Fusing the transcriptional inhibitory domain KRAB with STAT3 successfully blocked the transcription activity of STAT3 in cancer cells without affecting its function in the mitochondria and lysosomes. RESULTS: the expression of KRAB-STAT3 fusion protein inhibited the growth of tumor cells. CONCLUSIONS: The KRAB-STAT3 fusion protein provides a novel approach for drug development for the treatment of cancer or autoimmune diseases.
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Neoplasias , Enfermedades Neurodegenerativas , Regulación de la Expresión Génica , Humanos , Masculino , Neoplasias/patología , Factor de Transcripción STAT3/metabolismoRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Camrelizumab is a recently developed PD-1 inhibitor in China applied in treating different cancers including lung cancer. This study is designed to evaluate the efficacy, safety and prognostic factors for camrelizumab plus carboplatin and pemetrexed (CP) chemotherapy in treating patients with advanced lung adenocarcinoma. METHODS: Of 51 advanced lung adenocarcinoma patients with negative driver genes who received camrelizumab plus CP chemotherapy were recruited. These patients received four cycles of camrelizumab plus CP chemotherapy in a 21-day cycle. Then, camrelizumab, pemetrexed or camrelizumab plus pemetrexed was administered as maintenance therapy. RESULTS AND DISCUSSION: The rates of complete response, partial response, stable disease and progressive disease were 2.0%, 56.8%, 19.6% and 5.9%, respectively; while treatment response of 15.7% of patients was missing or not evaluable. The objective response and disease control rates were 58.8% and 78.4%, respectively. With a median follow-up period of 14.9 months (the follow-up duration ranged from 3.9 months to 24.3 months), 41 (83.4%) cases of disease progression and 22 (43.1%) cases of death were recorded. The median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI): 8.4-12.6 months) with a 1-year PFS rate of 36.3% and a 2-year PFS rate of 7.5%. In addition, the median overall survival (OS) was 18.7 months (95% CI: 16.4-21.0 months) with a 1-year OS rate of 79.1% and a 2-year OS rate of 30.4%. In consideration of safety, the most frequent adverse events were peripheral neuropathy (37.3%), neutropenia (37.3%), alopecia (35.3%), etc. and most of them were grade 1-2 and could be controlled. WHAT IS NEW AND CONCLUSION: Camrelizumab plus CP chemotherapy achieves favourable efficacy and tolerable adverse events in advanced lung adenocarcinoma patients.
Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/patología , Pemetrexed/efectos adversos , PronósticoRESUMEN
RATIONALE AND OBJECTIVES: This study aimed to evaluate the value of background parenchymal enhancement (BPE) and diffusion-weighted image (DWI) histogram features in differentiating among different molecular subtypes of breast cancers and investigate the relationship between BPE and DWI features. MATERIALS AND METHODS: We prospectively enrolled 142 patients with breast cancer between January and November 2018. All patients underwent breast magnetic resonance imaging before core needle biopsy. The quantitative BPE from dynamic enhanced images and the first-order histogram features extracted from DWI were analyzed. Univariate analysis of variance was used to compare differences in DWI histogram features and BPE characteristics among different molecular subtypes. Spearman test was used to compare the correlation between these imaging indexes. RESULTS: A total of 142 patients had 142 lesions, including 17 cases of triple-negative breast cancer, 12 cases of luminal A type breast cancer, 39 cases of luminal B type breast cancer, and 74 cases of human epidermal growth factor receptor 2-positive breast cancer. The apparent diffusion coefficient (ADC) 95th percentile, ADC kurtosis, and BPE were significantly different among 4 subtype groups (P < 0.05), especially between the triple-negative subtype and any other subtype (P < 0.05 in pairwise comparisons). There was a weak but significant correlation between BPE and kurtosis of ADC (r = -0.176, P = 0.036). CONCLUSIONS: Diffusion-weighted image histogram features (95th percentile ADC value and kurtosis value of ADC) and BPE features were different in the 4 molecular subtypes of breast cancer, especially in the triple-negative breast cancer subtype. Background parenchymal enhancement was negatively correlated with the kurtosis value of ADC.
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Neoplasias de la Mama/diagnóstico por imagen , Medios de Contraste , Imagen de Difusión por Resonancia Magnética/métodos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Mama/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
'Liuyuezaoyou' is an early-ripening cultivar selected from a bud mutation of Citrus grandis Osbeck 'Guanximiyou'. They were designated here as MT and WT, respectively. The fruit of MT matures about 45 days earlier than WT, which was accompanied by significant changes in key phytohormones, sugar compounds and organic acids. Recent studies have showed that microRNAs (miRNAs) play an important role in regulation of fruit ripening process. The aim of this study was to compare MT fruits with WT ones to uncover if miRNAs were implicated in the ripening of C. grandis. Fruits of both WT and MT at four developmental stages were analyzed using high-throughput sequencing and RT-PCR. Several independent miRNA libraries were constructed and sequenced. A total of 747 known miRNAs were identified and 99 novel miRNAs were predicted across all libraries. The novel miRNAs were found to have hairpin structures and possess star sequences. These results showed that transcriptome and miRNAs are substantially involved in a complex and comprehensive network in regulation of fruit ripening of this species. Further analysis of the network model revealed intricate interactions of miRNAs with mRNAs during the fleshy fruit ripening process. Several identified miRNAs have potential targets. These include auxin-responsive protein IAA9, sucrose synthase 3, V-type proton ATPase, NCED1 (ABA biosynthesis) and PL1/5 (pectate lyase genes), as well as NAC100 putative coordinated regulation networks, whose interactions with respective miRNAs may contribute significantly to fruit ripening of C. grandis.
Asunto(s)
Citrus/genética , Citrus/metabolismo , Frutas/genética , Frutas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Citrus/crecimiento & desarrollo , Correlación de Datos , Frutas/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN de Planta/genética , Transcriptoma/genéticaRESUMEN
BACKGROUND: To evaluate the imaging biomarkers of human epidermal growth factor receptor 2 (HER2) positive breast cancer in comparison to other molecular subtypes and to determine the feasibility of identifying hormone receptor (HR) status and lymph node metastasis status using volumetric-tumour histogram-based analysis through intravoxel incoherent motion (IVIM) and non-Gaussian diffusion. METHODS: This study included 145 breast cancer patients with 148 lesions between January and November in 2018. Among the 148 lesions, 74 were confirmed to be HER2-positive. The volumetric-tumour histogram-based features were extracted from the combined IVIM and non-Gaussian diffusion model. IVIM and non-Gaussian diffusion parameters obtained from images of the subjects with different molecular prognostic biomarker statuses were compared by Student's t test or the Mann-Whitney U test. The area under the curve (AUC), sensitivity, and specificity at the best cut-off point were reported. The Spearman correlation coefficient was calculated to analyse the correlations of clinical tumor nodule metastasis (TNM) stage and Ki67 with the IVIM and non-Gaussian diffusion parameters. RESULTS: The entropy of mean kurtosis (MK) was significantly higher in the HER2-positive group than in the HER2-negative group (p = 0.015), with an AUC of 0.629 (95% CI 0.546, 0.707), a sensitivity of 62.6%, and a specificity of 66.2%. For HR status, the MD 5th percentile was higher in the HR-positive group of HER2-positive breast cancer (p = 0.041), with an AUC of 0.643 (95% CI 0.523, 0.751), while for lymph node status, the entropy of mean diffusivity (MK) was lower in the lymph node positive group (p = 0.040), with an AUC of 0.587 (95% CI 0.504, 0.668). The clinical TNM stage and Ki67 index were correlated with several histogram parameters. CONCLUSION: Volumetric-lesion histogram analysis of IVIM and the non-Gaussian diffusion model can be used to provide prognostic information about HER2-positive breast cancers and potentially contribute to individualized anti-HER2 targeted therapy plans .
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Algoritmos , Neoplasias de la Mama/diagnóstico , Gráficos por Computador , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Carga Tumoral , Adulto , Área Bajo la Curva , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Difusión , Estudios de Factibilidad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/normas , Persona de Mediana Edad , Movimiento (Física) , Pronóstico , Curva ROC , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismoRESUMEN
BACKGROUND: This study aimed to investigate the diagnostic value of a dual-parametric 2D histogram classification method for breast lesions. METHODS: This study included 116 patients with 72 malignant and 44 benign breast lesions who underwent CAIPIRINHA-Dixon-TWIST-VIBE dynamic contrast-enhanced (CDT-VIBE DCE) and readout-segmented diffusion-weighted magnetic resonance examination. The volume of interest (VOI), which encompassed the entire lesion, was segmented from the last phase of DCE images. For each VOI, a 1D histogram analysis (mean, median, 10th percentile, 90th percentile, kurtosis and skewness) was performed on apparent diffusion coefficient (ADC) and volume transfer constant (Ktrans) maps; a 2D histogram image (Ktrans-ADC) was generated from the pixelwise aligned maps, and its kurtosis and skewness were calculated. Each parameter was correlated with pathological results using the Mann-Whitney test and receiver operating characteristic curve analysis. RESULTS: For the Ktrans histogram, the area under the curve (AUC) of the mean, median, 90th percentile and kurtosis had statistically diagnostic values (mean: 0.760; median: 0.661; 90th percentile: 0.781; and kurtosis: 0.620). For the ADC histogram, the AUC of the mean, median, 10th percentile, skewness and kurtosis had statistically diagnostic values (mean: 0.661; median: 0.677; 10th percentile: 0.656; skewness: 0.664; and kurtosis: 0.620). For the 2D Ktrans-ADC histogram, the skewness and kurtosis had statistically higher diagnostic values (skewness: 0.831, kurtosis: 0.828) than those of the 1D histogram (all P < 0.05). CONCLUSIONS: The dual-parametric 2D histogram analysis revealed better diagnostic accuracy for breast lesions than single parametric histogram analysis of either Ktrans or ADC maps.
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Neoplasias de la Mama/diagnóstico por imagen , Medios de Contraste/química , Imagen de Difusión por Resonancia Magnética , Adulto , Femenino , Humanos , Persona de Mediana Edad , Curva ROCRESUMEN
Overexpression of insulin growth factor 1 receptor (IGF-1R) and its ligand, insulin growth factor 1 (IGF-1), is related to treatment resistance and worse prognosis in many types of tumors. We reported recently that IGF-1R activation by IGF induces resistance to alectinib and stimulates the production of vascular endothelial growth factor, which indicates that IGF induces alectinib resistance and angiogenesis. This study aimed to determine the effect of bigeminal inhibition of anaplastic lymphoma kinase (ALK) and angiogenesis on human insulin growth factor 1 receptor (hIGF-1)-triggered drug resistance in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-positive lung cancer. Human lung adenocarcinoma H3122 and H2228 cells were exposed to a combination of insulin growth factor 1 receptor (IGF-1), alectinib, or apatinib. The effects of the combination therapy were examined using cell the Cell Counting Kit-8 assay, the colony-forming assay, the scratch test, and flow cytometry analysis, and the molecular mechanism was assessed by western blot. At nontoxic concentrations, apatinib restored alectinib sensitivity by increasing drug-induced apoptosis and inhibiting viability, migration, and invasion in IGF-triggered drug resistant cells. Moreover, we found that apatinib restored sensitivity to alectinib mainly through suppression of the ALK downstream signaling pathway and antiangiogenesis signaling. Taken together, our results indicate that simultaneous inhibition of ALK and vascular endothelial growth factor R2 by the combination of alectinib with apatinib may be useful for controlling progression of EML4-ALK fusion gene lung cancer by reversing ALK-TKI resistance and inhibiting angiogenesis.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Carbazoles/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Piperidinas/farmacología , Piridinas/farmacología , Adenocarcinoma del Pulmón/patología , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Humanos , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Neoplasias Pulmonares/patología , Proteínas de Fusión Oncogénica/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Receptor IGF Tipo 1/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Cryptococcal infection has become a public health challenge globally. However, information about cryptococcal infection in patients with hematological diseases remains relatively rare. METHODS: HIV-uninfected cryptococcosis cases with hematological diseases admitted to Huashan Hospital from January 2001 to December 2014 were reviewed. RESULTS: In total, 33 cryptococcosis patients were enrolled, including 12 malignant and 21 non-malignant hematological cases. Twenty-six patients had central nervous system (CNS) involvement, which was observed more often in patients with non-malignancies than with malignancies (20/21 vs. 6/12, P = 0.001) Most patients (25/26) with CNS infection were confirmed by cerebrospinal fluid (CSF) culture or smear, and 100% (20/20) of them tested positive for the CSF cryptococcal antigen test. Eighteen out of 26 cryptococcal meningitis patients were treated with amphotericin B (AmB)-based therapy, 16 of them with AmB deoxycholate (d-AmB) and 2 patients with liposomal AmB. The clinical success rate was 55.6%. D-AmB was well-tolerated at 0.35-0.59 mg/kg/d (median 0.43 mg/kg/d) and only 12 patients had mild adverse events. CONCLUSIONS: CNS cryptococcal infection was more frequent in patients with hematological non-malignancies, and cryptococcal antigen test as well as the CSF fungal culture or smear are suggested for early diagnosis. D-AmB could be used as an alternative therapy for CNS-infected patients with hematological diseases.
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Antifúngicos/uso terapéutico , Criptococosis/etiología , Enfermedades Hematológicas/microbiología , Adolescente , Adulto , Anciano , Anfotericina B/uso terapéutico , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Infecciones Fúngicas del Sistema Nervioso Central/microbiología , Criptococosis/tratamiento farmacológico , Ácido Desoxicólico/uso terapéutico , Combinación de Medicamentos , Femenino , Enfermedades Hematológicas/complicaciones , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/microbiología , Humanos , Masculino , Meningitis Criptocócica/tratamiento farmacológico , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria , Adulto JovenRESUMEN
Dectin-2 is a C-type lectin receptor that can recognize critical structures of fungi and involve in the host immune response after pulmonary fungal infections. We aimed to investigate the association between Dectin-2 genetic polymorphisms and cryptococcosis among a series of human immunodeficiency virus (HIV)-uninfected Chinese patients. In this case control study, a total of 251 patients with cryptococcosis and 464 healthy controls were included. One tag-single nucleotide polymorphism (SNP) (rs11045418) located at 5'-flanking region of Dectin-2 gene was selected and genotyped in this study. Among 251 patients, there were 108 (43%) meningitis patients including 73 (67.7%) healthy ones, 74 (29.5%) pulmonary infected patients including 49 (66.2%) healthy ones, and 69 (27.5%) patients with both neural and pulmonary infection including 38 (55.1%) immunocompetent ones. One hundred and forty-three (74 plus 69) patients with pulmonary cryptococcosis and 177 (108 plus 69) patients with cryptococcal meningitis were compared with controls, respectively. Three samples from 143 pulmonary infected patients failed in genotyping. There was a significant difference between 86 immunocompetent pulmonary infected patients and controls in the overdominant model (C/T vs. T/T + C/C; OR, 0.59; 95%CI, 0.37-0.94; P, .026). Similar but not significant difference was found between the overall pulmonary infected patients and the controls in the overdominant model (OR, 0.77; 95%CI, 0.52-1.12; P, .17). No such difference was found between controls and patients with cryptococcal meningitis. Our study firstly showed a genetic association between Dectin-2 and pulmonary cryptococcosis.
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Criptococosis/genética , Criptococosis/inmunología , Predisposición Genética a la Enfermedad , Infecciones por VIH/complicaciones , Lectinas Tipo C/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , China , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells in vitro was significantly enhanced after inhibition of P-gp by verapamil. The impact of two model P-gp inhibitors, verapamil and itraconazole, on brain/plasma ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally infected with Cryptococcus neoformans. In uninfected mice, the brain/plasma ratios of AMB were increased 15 min (3.5 versus 2.0; P < 0.05) and 30 min (5.2 versus 2.8; P < 0.05) after administration of verapamil or 45 min (6.0 versus 3.9; P < 0.05) and 60 min (5.4 versus 3.8; P < 0.05) after itraconazole administration. The increases in brain/plasma ratios were also observed in infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU in infected mice were significantly lower in AMB-plus-itraconazole or verapamil groups than in the untreated group (P < 0.005), but none of the treatments protected the mice from succumbing to the infection. In conclusion, we demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB, suggesting that AMB is a P-gp substrate.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Anfotericina B/farmacocinética , Antifúngicos/farmacocinética , Barrera Hematoencefálica/efectos de los fármacos , Criptococosis/tratamiento farmacológico , Verapamilo/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Anfotericina B/farmacología , Animales , Antifúngicos/farmacología , Transporte Biológico/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/microbiología , Corteza Cerebral/patología , Recuento de Colonia Microbiana , Criptococosis/microbiología , Criptococosis/mortalidad , Criptococosis/patología , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/crecimiento & desarrollo , Cryptococcus neoformans/patogenicidad , Sinergismo Farmacológico , Quimioterapia Combinada , Inyecciones Intraventriculares , Itraconazol/farmacología , Masculino , Ratones , Análisis de SupervivenciaRESUMEN
Lemna turionifera is native to North America and northern Asia, with significant potential for industrial wastewater remediation. The complete nucleotide sequence of the L. turionifera chloroplast genome (cpDNA) was determined. The cpDNA is a circular molecule of 166,606 bp and containing a pair of inverted repeats (IRs) measuting 31,663 bp each. These IRs are flanked by a small single-copy region of 13,542 bp and a large single-copy region of 89,738 bp. The chloroplast genome of L. turionifera consisted of 112 unique genes, including 78 protein-encoding genes, 30 tRNA genes, and four rRNA genes. The phylogenetic analysis utilizing cpDNA provided a well-supported resolution of the relationships among subfamilies within the Araceae family. Our findings indicated a close relationship between L. turionifera and a clade consisting of L. minor, L. japonica, and L. gibba. The availability of the complete chloroplast genome sequence of L. turionifera presents valuable data for future phylogenetic investigations within the Lemnaceae family.
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Information about wildlife diets is crucial for comprehending how species adapt to varying environments in fragmented habitats and for developing effective conservation strategies. White-headed langurs (Trachypithecus leucocephalus) are exclusively found in fragmented limestone forests in southwestern China. To investigate the effects of habitat fragmentation on langurs' diets, we collected published dietary data and relevant environmental factors spanning from 1996 to 2021 at two regions with different degrees of fragmentation (Banli > Bapen), from 10 studies (three of Banli and seven of Bapen). The results demonstrated that the diets of white-headed langurs were significantly influenced by environmental factors, including habitat fragmentation, annual rainfall, and mean annual temperature. Food item diversity index was significantly and positively affected by the fragmentation index, the higher fragmentation the langurs suffered, the more diverse food items they consumed. Besides, fruit consumption was negatively influenced by annual rainfall and the consumption of other items was influenced by mean annual temperature. Notably, although there are no significant differences in the feeding proportions of food items or food item diversity indices were observed between the Banli and Bapen groups, the Banli groups extensively consumed ground-supported kudzu (Pueraria montana var. lobata), a plant rarely recorded in the dietary preferences of the Bapen groups, implying that the large plants likely lacking in the fragmented limestone forests. Our findings provide evidence of the major impact of habitat fragmentation on the dietary composition of white-headed langurs, highlighting the need of considering the possibility that the habitats of the white-headed langurs have all undergone extreme fragmentation, inferring the conservation efforts should prioritize protecting native vegetation and reducing human disturbance.
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BACKGROUND: Components of excretory/secretory products (ESPs) of helminths have been proposed as vaccine targets and shown to play a role in modulating host immune responses for decades. Such research interest is further increased by the discovery of extracellular vesicles (EVs) in the ESPs of parasitic worms. Although efforts have been made to reveal the cargos of EVs, little is known about the proteomic differences between EVs and canonical ESPs released by parasitic worms from animals. METHODS: The total ESPs of Haemonchus contortus (barber's pole worm) were obtained by short-term in vitro culturing of young adult worms, and small EVs were isolated from ESPs using an ultracentrifugation method. Data-dependent acquisition (DDA) label-free Nano-LC-MS/MS was used to quantify the proteomic difference between small EVs and EV-depleted ESPs of H. contortus. Functional annotation and enrichment of the differential proteins were performed regarding cellular components, molecular functions, pathways, and/or biological processes. RESULTS: A total of 1697 proteins were identified in small EVs and EV-depleted ESPs of H. contortus adult worms, with 706 unique proteins detected in the former and 597 unique proteins in the latter. It was revealed that proteins in small EVs are dominantly cytoplasmic, whereas proteins in EV-depleted ESPs are mainly extracellular; canonical ESPs such as proteases and small GTPases were abundantly detected in small EVs, and SCP/TAP-, DUF-, and GLOBIN domain-containing proteins were mainly found in EV-depleted ESPs. Compared with well-characterised proteins in small EVs, about 50% of the proteins detected in EV-depleted ESPs were poorly characterised. CONCLUSIONS: There are remarkable differences between small EVs and EV-depleted ESPs of H. contortus in terms of protein composition. Immune modulatory effects caused by nematode ESPs are possibly contributed mainly by the proteins in small EVs.
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Vesículas Extracelulares , Haemonchus , Nematodos , Animales , Proteómica , Espectrometría de Masas en Tándem , Haemonchus/metabolismoRESUMEN
The high-affinity K+ transporter (HAK) family, the most prominent potassium transporter family in plants, which involves K+ transport, plays crucial roles in plant responses to abiotic stresses. However, the HAK gene family remains to be characterized in quinoa (Chenopodium quinoa Willd.). We explored HAKs in quinoa, identifying 30 members (CqHAK1-CqHAK30) in four clusters phylogenetically. Uneven distribution was observed across 18 chromosomes. Furthermore, we investigated the proteins' evolutionary relationships, physicochemical properties, conserved domains and motifs, gene structure, and cis-regulatory elements of the CqHAKs family members. Transcription data analysis showed that CqHAKs have diverse expression patterns among different tissues and in response to abiotic stresses, including drought, heat, low phosphorus, and salt. The expressional changes of CqHAKs in roots were more sensitive in response to abiotic stress than that in shoot apices. Quantitative RT-PCR analysis revealed that under high saline condition, CqHAK1, CqHAK13, CqHAK19, and CqHAK20 were dramatically induced in leaves; under alkaline condition, CqHAK1, CqHAK13, CqHAK19, and CqHAK20 were dramatically induced in leaves, and CqHAK6, CqHAK9, CqHAK13, CqHAK23, and CqHAK29 were significantly induced in roots. Our results establish a foundation for further investigation of the functions of HAKs in quinoa. It is the first study to identify the HAK gene family in quinoa, which provides potential targets for further functional study and contributes to improving the salt and alkali tolerance in quinoa.
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The white-headed black langur (Trachypithecus leucocephalus) is exclusively distributed in the karst forests and is critically endangered owing to habitat fragmentation. Gut microbiota can provide physiological data for a comprehensive study of the langur's response to human disturbance in the limestone forest; to date, data on spatial variations in the langurs' gut microbiota are limited. In this study, we examined intersite variations in the gut microbiota of white-headed black langurs in the Guangxi Chongzuo White-headed Langur National Nature Reserve, China. Our results showed that langurs in the Bapen area with a better habitat had higher gut microbiota diversity. In the Bapen group, the Bacteroidetes (13.65% ± 9.73% vs. 4.75% ± 4.70%) and its representative family, Prevotellaceae, were significantly enriched. In the Banli group, higher relative abundance of Firmicutes (86.30% ± 8.60% vs. 78.85% ± 10.35%) than the Bapen group was observed. Oscillospiraceae (16.93% ± 5.39% vs. 16.13% ± 3.16%), Christensenellaceae (15.80% ± 4.59% vs. 11.61% ± 3.60%), and norank_o__Clostridia_UCG-014 (17.43% ± 6.64% vs. 9.78% ± 3.83%) were increased in comparison with the Bapen group. These intersite variations in microbiota diversity and composition could be accounted for by differences in food resources caused by fragmentation. Furthermore, compared with the Banli group, the community assembly of gut microbiota in the Bapen group was influenced by more deterministic factors and had a higher migration rate, but the difference between the two groups was not significant. This might be attributed to the serious fragmentation of the habitats for both groups. Our findings highlight the importance of gut microbiota response for the integrity of wildlife habitats and the need in using physiological indicators to study the mechanisms by which wildlife responds to human disturbances or ecological variations.
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With the pollution of the environment and the acceleration of the social rhythm, the prevalence of tumors has increased year by year, and tumors have brought huge pain and inconvenience to patients. However, traditional nursing work consumes a lot of manpower and material resources, but it is difficult to improve the happiness of cancer patients, and it also brings a lot of troubles to many nursing workers. Based on the above reasons, we reengineered the traditional nursing process based on the BPR theory and applied the new process to the analysis of the management effect of cancer patients after oral chemotherapy drugs. The data shows that there are 23 patients with no pressure ulcer risk (score greater than 19) before care, 27 patients with low risk (15-19 points), 32 patients with moderate risk (13-14 points), and 18 people at high risk (less than 12 points). After nursing, there were 82 patients with no pressure ulcer risk, 10 patients with low risk, 7 patients with moderate risk, and 1 patient with high risk. This shows that the risk of pressure ulcers in patients with cancer after the use of chemotherapy drugs is significantly reduced compared with those without nursing. Nursing intervention can improve the psychological state of cancer patients during the recovery period, and nursing intervention can promote the compliance of cancer patients in various aspects of rehabilitation.