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1.
Mol Cell Probes ; 75: 101959, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579915

RESUMO

Human Toll-like receptor (TLR) family plays a crucial role in immunity and cancer progression. However, the specific role of human Toll-like receptor 4 (TLR4) in kidney renal clear cell carcinoma (KIRC) remains obscure. Thus, we used single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies to evaluate the expression and prognostic value of TLR4 in KIRC. In our study, we observed that TLR4 was over expressed in KIRC tissues compared to normal renal tissues. And the expression of TLR4 was higher in macrophages/monocytes than other cell types. Besides, there is a close association between TLR4 expression and immune cell infiltration (Neutrophils, Macrophages, T cells and B cells) in KIRC. Immunohistochemical staining also showed that TLR4 was overexpressed in inflammatory infiltration renal tissue compared with normal tissue. Meanwhile, high expression of TLR4 exhibited correlations with improved survival, lower tumor grade and stage. Interestingly, the protective significance of TLR4 only showed in female patients (HR = 0.37, P < 0.01), other than male patients (HR = 0.71, P = 0.08) with KIRC. Consistently, KIRC samples with lymph node metastasis showed lower expression of TLR4. Knockdown of TLR4 in 786-O cell line increased cell proliferation and clonogenic capacity. In summary, this study found TLR4 could inhibit the progression of kidney cancer and was associated with improved survival in KIRC. The overexpression of TLR4 in macrophages and the close association between TLR4 and immune cell infiltration also underline the critical role of TLR4 in building the immune microenvironment for kidney cancer. These results may offer insights into the mechanism and immune microenvironment of kidney cancer.


Assuntos
Carcinoma de Células Renais , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Receptor 4 Toll-Like , Feminino , Humanos , Masculino , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Macrófagos/metabolismo , Prognóstico , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética
2.
Scand J Immunol ; 97(6): e13254, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36626120

RESUMO

The study aimed to investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in antinuclear antibodies (ANAs) test samples retrospectively. The laboratory data and clinical details of patients with positive anti-RR antibodies were collected and analysed between December 2017 and May 2022 in the First Affiliated Hospital of Dalian Medical University. A total of 72 665 patients were tested for ANAs. There were 45 632 patients discovered with positive ANAs (62.80%), only 131 patients presented with anti-RR antibodies (0.18%), among which only 68 patients were hospitalized patients with a definitive diagnosis. Among the 68 patients with a definitive diagnosis, 8 of 68 (11.8%) had autoimmune diseases, and 19 of 68 (27.9%) had renal diseases. Other diseases included liver disease, pulmonary disease, cerebral ischemia, cerebral infarction, chronic cardiac failure and venous thromboembolism. The detection rate of high titre(≥1:1000) anti-RR antibodies is significantly higher in autoimmune diseases.


Assuntos
Doenças Autoimunes , População do Leste Asiático , Humanos , Estudos Retrospectivos , Anticorpos Antinucleares , Doenças Autoimunes/diagnóstico , Povo Asiático
3.
BMC Cancer ; 23(1): 1267, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129784

RESUMO

Head and neck squamous carcinoma (HNSC) poses a significant public health challenge due to its substantial morbidity. Nevertheless, despite advances in current treatments, the prognosis for HNSC remains unsatisfactory. To address this, single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies were conducted to examine the role of MYO5A (Myosin VA) in HNSC. Our investigation revealed an overexpression of MYO5A in HNSC that promotes HNSC migration in vitro. Remarkably, knockdown of MYO5A suppressed vimentin expression. Furthermore, analyzing the TCGA database evidenced that MYO5A is a risk factor for human papillomavirus positive (HPV+) HNSC (HR = 0.81, P < 0.001). In high MYO5A expression HNSC, there was a low count of tumor infiltrating lymphocytes (TIL), including activated CD4+ T cells, CD8+ T cells, and B cells. Of note, CD4+ T cells and B cells were positively associated with improved HPV+ HNSC outcomes. Correlation analysis demonstrated a decreased level of immunostimulators in high MYO5A-expressing HNSC. Collectively, these findings suggest that MYO5A may promote HNSC migration through vimentin and involve itself in the process of immune infiltration in HNSC, advancing the understanding of the mechanisms and treatment of HNSC.


Assuntos
Neoplasias de Cabeça e Pescoço , Miosina Tipo V , Infecções por Papillomavirus , Humanos , Vimentina/genética , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Processos Neoplásicos , Prognóstico , Linfócitos do Interstício Tumoral , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/genética
4.
BMC Psychiatry ; 23(1): 664, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684592

RESUMO

BACKGROUND: Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but can also endanger flight safety. Hence, we aimed to quickly and effectively relieve symptoms and restore cognitive function by forming a consensus of Chinese experts on the pharmacological treatment of acute stress disorder in pilots using the Delphi method. METHODS: Relevant literature was searched to enumerate the current status of pharmacological treatment of acute stress disorder in pilots, followed by two rounds of expert consultation and discussion according to the listed status of the survey using the Delphi method. A descriptive statistical method was used to analyze the basic information, authority coefficients, concentration of opinions, and survey items of the experts to develop a consensus on the pharmacological treatment of acute stress disorder in pilots. RESULTS: A total of 16 experts in psychiatry, pharmacology, and aerospace medicine from different provinces and cities across China were invited for consultation. The recovery rate of the two rounds of consultation was 100%, and the expert authority coefficients were 0.897 and 0.906, respectively. Kendall's coefficient of concordance of indicators at all levels was 0.564-0.594 (p < 0.01). Based on the number of votes received, alprazolam tablets (16), eszopiclone tablets (15), and lorazepam tablets (14) were recommended for the treatment of excitatory psychomotor symptoms of acute stress disorder; paroxetine tablets (15) and sertraline tablets (15) were available for psychomotor depressive symptoms; olanzapine tablets (15), olanzapine orally disintegrating tablets (14), and quetiapine fumarate tablets (14) were selected for psychotic symptoms. CONCLUSIONS: This study formed a consensus on rapid and effective pharmacological treatment for different symptoms of acute stress disorder pilots, which provides a reference for clinical treatment.


Assuntos
População do Leste Asiático , Pilotos , Transtornos de Estresse Traumático Agudo , Humanos , Consenso , Técnica Delphi , Olanzapina , Pilotos/psicologia
5.
BMC Pulm Med ; 22(1): 72, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35216582

RESUMO

BACKGROUND: High altitude pulmonary edema (HAPE) is a hypoxia-induced non-cardiogenic pulmonary edema that typically occurred in un-acclimatized lowlanders, which inevitably leads to life-threatening consequences. Apart from multiple factors involved, the genetic factors also play an important role in the pathogenesis of HAPE. So far, researchers have put more energy into the nuclear genome and HAPE, and ignored the relationship between the mitochondrion DNA (mtDNA) variants and HAPE susceptibility. METHODS: We recruited a total of 366 individuals including 181 HAPE patients and 185 non-HAPE populations through two times. The first time, 49 HAPE patients and 58 non-HAPE individuals were performed through whole mtDNA sequences to search the mutations and haplogroups. The second time, 132 HAPE patients and 127 non-HAPE subjects were collected to apply verifying these mutations and haplogroups of mtDNA with the routine PCR method. RESULTS: We analyzed and summarized the clinical characteristics and sequence data for the 49 HAPE patients and 58 non-HAPE individuals. We found that a series of routine blood indexes including systolic arterial blood pressure (SBP), heart rate (HR), white blood cell (WBC), and C-reactive protein (CRP) in the HAPE group presented higher and displayed significant differences compared with those in the non-HAPE group. Although the average numbers of variants in different region and group samples were not statistically significant (P > 0.05), the mutation densities of different regions in the internal group showed significant differences. Then we found two mutations (T16172C and T16519C) associated with the HAPE susceptibility, the T16172C mutation increased the risk of HAPE, and the T16519C mutation decreased the HAPE rating. Furthermore, the two mutations were demonstrated with 132 HAPE patients and 127 non-HAPE individuals. Unfortunately, all the haplogroups were not associated with the HAPE haplogroups. CONCLUSIONS: We provided evidence of differences in mtDNA polymorphism frequencies between HAPE and non-HAPE Han Chinese. Genotypes of mtDNA 16172C and 16519C were correlated with HAPE susceptibility, indicating the role of the mitochondrial genome in the pathogenesis of HAPE.


Assuntos
Altitude , Edema Pulmonar , Povo Asiático/genética , China , DNA Mitocondrial/genética , Humanos , Mitocôndrias
6.
J Xray Sci Technol ; 30(6): 1085-1097, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938282

RESUMO

OBJECTIVE: In order to solve the problem of image quality degradation of CT reconstruction under sparse angle projection, we propose to develop and test a new sparse angle CT reconstruction method based on group sparse. METHODS: In this method, the group-based sparse representation is introduced into the statistical iterative reconstruction framework as a regularization term to construct the objective function. The group-based sparse representation no longer takes a single patch as the minimum unit of sparse representation, while it uses Euclidean distance as a similarity measure, thus it divides similar patch into groups as basic units for sparse representation. This method fully considers the local sparsity and non-local self-similarity of image. The proposed method is compared with several commonly used CT image reconstruction methods including FBP, SART, SART-TV and GSR-SART with experiments carried out on Sheep_Logan phantom and abdominal and pelvic images. RESULTS: In three experiments, the visual effect of the proposed method is the best. Under 64 projection angles, the lowest RMSE is 0.004776 and the highest VIF is 0.948724. FSIM and SSIM are all higher than 0.98. Under 50 projection angles, the index of the proposed method remains achieving the best image quality. CONCLUSION: Qualitative and quantitative results of this study demonstrate that this new proposed method can not only remove strip artifacts, but also effectively protect image details.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Ovinos , Animais , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Artefatos , Tomografia Computadorizada por Raios X/métodos
7.
Dermatol Ther ; 33(6): e14305, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32926496

RESUMO

Mevalonate pathway plays a key role in skin physiological process in human. Recently, it has been reported that mutation of some genes in the mevalonate pathway cause disseminated superficial actinic porokeratosis (DSAP). But the pathogenesis is still unknown. Pravastatin (PRA), one of HMG-CoA reductase (HMGCR) inhibitors, has been found to inhibit cells proliferation, including keratinocytes (KCs). In this study, we use PRA to block the mevalonate pathway in KCs with or without the down-stream intermediate products replenishment. The results demonstrated that PRA strongly inhibited proliferation of KCs and caused the G0 /G1 arrest. When some down-stream intermediate products were added, only cholesterol (CH) could partially rescue the inhibition effect of PRA on KCs proliferation, but not other products, such as mevalonic acid, farnesyl pyrophosphate or geranylgeranyl pyrophosphate. Mechanistic analysis revealed that PRA down-regulated expression of cyclin B1, but up-regulated cyclin E and p21 expression. And PRA increased the phosphorylation level of Protein Kinase B (AKT) but decreased the phosphorylation level of Extracellular Signal Regulated Kinase (ERK1/2). CH could attenuate the elevated cyclin E and activated AKT induced by PRA. These results indicated that CH could rescue the proliferation inhibition of KCs caused by PRA, which laid a foundation for elucidating the pathogenesis of DSAP clearly.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Pravastatina , Ciclo Celular , Proteínas de Ciclo Celular , Proliferação de Células , Colesterol , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Pravastatina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
8.
J Am Chem Soc ; 141(1): 48-52, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30569704

RESUMO

The synthesis of graphdiyne with an ordered internal structure is highly attractive for its various scientific and application investigations. We reported herein a rational method to fabricate a graphdiyne analogue with the help of supramolecular chemistry. The introduction of π-π/CH-π interactions controlled the conformations of the precursors and afforded multilayer graphdiyne analogue Ben-GDY through the wet chemical method. The in-plane periodicity of the multilayer Ben-GDY was corroborated by transmission electron microscopy and selected area electron diffraction, which showed a pattern well matched with ABC-style stacking.

10.
Inorg Chem ; 57(5): 2472-2479, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29442500

RESUMO

Four seven-nuclearity 3d-4f heterometallic cluster {Fe6LnO28} substituted polyoxometalates (HPz)11K4Fe6Ln(µ3-O)2(B-α-GeW9O34)2(GeW6O26)· xH2O (1-Ln, Pz = piperazine, Ln = Tb, Dy, Ho, Er for x = 27, 25, 25, 24, respectively) have been hydrothermally prepared and structurally characterized by single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectrometry, thermogravimetric analyses, elemental analyses, and electrospray ionization mass spectrometry. Single-crystal X-ray diffraction analyses revealed that 1-Ln contain an unprecedented banana-shaped polyanion constructed from an iron-lanthanide heterometallic {Fe6LnO28} cluster, two trilacunary {B-α-GeW9O34} units, and one hexalacunary {GeW6O26} fragment. The magnetic susceptibility surveying proved the presence of antiferromagnetic coupling in 1-Ln.

11.
J Clin Lab Anal ; 32(4): e22361, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29168582

RESUMO

BACKGROUND: Our article aims to evaluate the proportion of monospecific antinuclear antibodies (ANA) and polyclonal ANAs in patients with autoimmune diseases based on the results of an ANA panel and to evaluate the efficiency of trait ANAs as a novel diagnostic tool. This study also aims to investigate immunoglobulin production in autoimmune diseases by detecting different antibodies. METHODS: The serum ANA profile of 634 patients with autoimmune diseases was analyzed using the immunoblot method. A specific formula was developed in an effort to calculate the theoretical proportion of monospecific ANA (TPM) in different disease groups. Different IgM, IgG, and IgE variants for several pathologies were detected. RESULTS: The observed proportions of monospecific ANAs (OPM) were all lower than the predicted TPM in autoimmune diseases. Polyclonal ANAs were predominant in patients with systemic lupus erythematosus (SLE). There were statistical differences in OPM and TPM in all disease groups (P < .001). Receiver operating characteristic curve (ROC curve) analysis of trait ANAs between the SLE group and the control groups indicated an area under the curve of 0.916. Differences were found in IgM of Toxoplasma gondii (TOXO) and IgG of hepatitis C virus (HCV) and Treponema pallidum (TP) when comparing the various disease groups to the control group. CONCLUSION: The higher TPM suggests that polyclonal differentiation is the major mechanism of ANA in autoimmune diseases. Trait ANA is potentially a valuable new index for diagnosis in SLE. Further investigation is needed to understand the link between B-cell differentiation and autoimmune diseases.


Assuntos
Anticorpos Antinucleares/sangue , Doenças Autoimunes/diagnóstico , Biomarcadores/sangue , Adulto , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Feminino , Humanos , Immunoblotting , Lúpus Eritematoso Sistêmico , Masculino , Pessoa de Meia-Idade
12.
Des Monomers Polym ; 20(1): 458-467, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29491817

RESUMO

A series of tertiary amine-based hyperbranched poly(amine-ester)s have been synthesized by Michael addition polymerization of trifunctional monomer, TMEA and difunctional monomer, diacylates in chloroform, and the resultant polymers were subsequently treated with mercaptoethenol or 1-dodecanethiol for improving stability in storage. The caption efficiency of mercaptoethanol is much better than that of 1-dodecanthiol. Kinetic study reveals that the thiol group is consumed faster than the acrylate group when the polymerization with feed molar ratio of diacrylate/TMEA = 2/1 was carried out. At initial polymerization, monomer conversion increases fast, but the molecular weights increase slowly and sharp increase of the molecular weight occurs at the final polymerization. The hyperbranched polymers were well characterized by 1H NMR spectra and TD-SEC, and DBs of the polymers obtained are between 0.6 and 0.82, as well as the molar ratios of diacrylate/TMEA in the hyperbranched polymers are between 1.60 and 1.82. The fluorescence efficiency and quantum yields of HypET20, HypHT24 and HypDT24 has the following sequence: HypET20 > HypHT24 > HypDT24.

13.
Exp Eye Res ; 145: 327-336, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26874036

RESUMO

Single-cell injection after immunocytochemistry is a reliable technique for classifying neurons by their morphological structure and their expression of a particular protein. The aim of the present study was to classify the morphological types of calbindin D28k-immunoreactive retinal ganglion cells in the mouse using single-cell injection after immunocytochemistry, to estimate the density of calbindin D28k-immunoreactive retinal ganglion cells in the mouse retina. Calbindin D28k is an important calcium-binding protein that is widely expressed in the central nervous system. Calbindin D28k-immunoreactive retinal ganglion cells were identified by immunocytochemistry and then iontophoretically injected with the lipophilic dye, DiI. Subsequently, the injected cells were imaged by confocal microscopy to classify calbindin D28k-immunoreactive retinal ganglion cells based on their dendritic ramification depth within the inner plexiform layer, field size, and morphology. The cells were heterogeneous in morphology: monostratified or bistratified, with small to large dendritic field size and sparse to dense dendritic arbors. At least 10 different morphological types (CB1-CB10) of calbindin D28k-immunoreactive retinal ganglion cells were found in the mouse retina. The density of each cell type was quite variable (1.98-23.76%). The density of calbindin D28k-immunoreactive cells in the ganglion cell layer of the mouse retina was 562 cells/mm(2), 8.18% of calbindin D28k-immunoreactive cells were axon-less displaced amacrine cells, 91.82% were retinal ganglion cells, and approximately 18.17% of mouse retinal ganglion cells expressed calbindin D28k. The selective expression of calbindin D28k in cells with different morphologies may provide important data for further physiological studies of the mouse retina.


Assuntos
Calbindina 1/metabolismo , Células Ganglionares da Retina/citologia , Animais , Contagem de Células , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Células Ganglionares da Retina/metabolismo
14.
Biomed Chromatogr ; 30(6): 962-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26467669

RESUMO

Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK-positive nonsmall-cell lung cancer. A rapid and simple high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of crizotinib in rat plasma using a chemical synthetic compound buspirone as the internal standard (IS). The plasma samples were pretreated by a simple protein precipitation with methanol-acetonitrile (1:1, v/v). Chromatographic separation was successfully achieved on an Agilent Zorbax XDB C18 column (2.1 × 50 mm, 3.5 µm). The gradient elution system was composed of 0.1% formic acid aqueous solution and 0.1% formic acid in methanol solution. The flow rate was set at 0.50 mL/min. The multiple reaction monitoring was based on the transitions of m/z = 450.3 → 177.1 for crizotinib and 386.2 → 122.2 for buspirone (IS). The assay was successfully validated to demonstrate the selectivity, matrix effect, linearity, lower limit of quantification, accuracy, precision, recovery and stability according to the international guidelines. The lower limit of quantification was 1.00 ng/mL in 50 µL of rat plasma. This LC-MS/MS assay was successfully applied to the quantification and pharmacokinetic study of crizotinib in rats after intravenous and oral administration of crizotinib. The oral absolute bioavailability of crizotinib in rats was 68.6 ± 9.63%. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Cromatografia Líquida/métodos , Inibidores de Proteínas Quinases/farmacocinética , Pirazóis/farmacocinética , Piridinas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Calibragem , Crizotinibe , Controle de Qualidade , Ratos
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(3): 357-60, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-27264821

RESUMO

OBJECTIVE: To provide mutation analysis and prenatal diagnosis for a family affected with congenital factor VII(FVII) deficiency. METHODS: DNA was extracted from peripheral blood samples from the proband and his parents. All exons and flanking sequence of the FVII gene were amplified with PCR and subjected to direct sequencing. Prenatal diagnosis was performed by amniocentesis. RESULTS: A homozygous mutation (NM_000131.3) c.572-1G>A was identified in the proband. Both parents of the fetus were carriers of the mutation. CONCLUSION: A method for molecular diagnosis of congenital factor VII deficiency was established and successfully applied for an affected family.


Assuntos
Deficiência do Fator VII/genética , Mutação , Diagnóstico Pré-Natal , Humanos , Recém-Nascido , Masculino
16.
Clin Lab ; 61(11): 1709-14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26731997

RESUMO

BACKGROUND: The status of immune response to HCV infection cannot be accurately predicted by the HCV antibody test alone. Our paper aims to explore differences in total activity, quantity, and affinity of anti-HCV antibodies in patients with HCV infection, proposing a novel measurement of antibody affinity and providing a promising understanding into immune response to HCV. METHODS: Serum samples from 106 patients with HCV infection were collected. Anti-HCV antibodies, HCV RNA, ALT, and AST were measured. The samples were divided into three groups based on ALT, AST level (both normal, one abnormal, and both abnomal) and HCV-RNA level (negative, low viral load, and high viral load). Differences in total activity, quantity, and affinity of anti-HCV antibodies were analyzed. RESULTS: The quantity of anti-HCV antibodies in the normal ALT and AST groups were significantly lower than that of the other two groups (p < 0.05). In contrast, the antibody affinity of the normal ALT and AST groups was significantly higher than that detected in the other two groups (p < 0.05). The total activity and quantity of anti-bodies in the low and high viral load groups were significantly higher than those measured in the HCV RNA-negative group (p < 0.05). The HCV RNA-negative group had a significantly higher antibody affinity than the other two groups (p < 0.05). HCV-RNA level was negatively correlated with affinity (p < 0.05). CONCLUSIONS: Our results indicate that the total activity, quantity, and affinity of anti-HCV antibodies may reflect viral load in patients infected with HCV and could serve as valuable information for clinical applications.


Assuntos
Afinidade de Anticorpos , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C/imunologia , Hepatite C/virologia , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Bioprocess Biosyst Eng ; 38(10): 1845-54, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26091897

RESUMO

A combination of microbial strain improvement and statistical optimization is investigated to maximize echinocandin B (ECB) production from Aspergillus nidulans ZJB-0817. A classical sequential mutagenesis was studied first by using physical (ultraviolet irradiation at 254 nm) and chemical mutagens (lithium chloride and sodium nitrite). Mutant strain ULN-59 exhibited 2.1-fold increase in ECB production to 1583.1 ± 40.9 mg/L when compared with the parent strain (750.8 ± 32.0 mg/L). This is the first report where mutagenesis is applied in Aspergillus to improve ECB production. Further, fractional factorial design and central composite design were adopted to optimize the culture medium for increasing ECB production by the mutant ULN-59. Results indicated that four culture media including peptone, K2HPO4, mannitol and L-ornithine had significant effects on ECB production. The optimized medium provided another 1.4-fold increase in final ECB concentration to 2285.6 ± 35.6 mg/L compared to the original medium. The results of this study indicated the combined application of a classical mutation and medium optimization can improve effectively ECB production from A. nidulans and could be a promising tool to improve other secondary metabolites production by fungal strains.


Assuntos
Aspergillus nidulans/fisiologia , Técnicas de Cultura Celular por Lotes/métodos , Meios de Cultura/metabolismo , Equinocandinas/biossíntese , Proteínas Fúngicas/biossíntese , Melhoramento Genético/métodos , Mutagênicos/farmacologia , Aspergillus nidulans/efeitos dos fármacos , Aspergillus nidulans/efeitos da radiação , Equinocandinas/genética , Proteínas Fúngicas/genética , Mutação/efeitos dos fármacos , Mutação/genética , Mutação/efeitos da radiação , Especificidade da Espécie , Raios Ultravioleta
18.
ACS Omega ; 9(18): 20378-20387, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737016

RESUMO

To further explore cocombustion technology with biogas and coal, a series of numerical simulations have been carried out to analyze the effects of the cocombustion ratio ξ, height of biogas nozzle HGN, and tilt angle of burner θBN on combustion characteristics in a 300 MW four-corner tangential boiler furnace. Three types of biogas are gasified from straw, sawdust, and raw wood when air serves as the gasification agent. The velocity field, temperature field, and NO emissions have been comprehensively analyzed when the values of ξ, HGN, and θBN range, respectively, from 0.02 to 0.12, from 17.3 to 20.3 m, and from -15° to +15°. Results showed that the NO concentration at the furnace outlet monotonously decreased with ξ. The injection of biogas reduces both the peak temperature of the entire boiler furnace and the NO concentration at the furnace outlet. The NO emission concentration decreases with the increased ξ value for all types of biogases. The cocombustion with sawdust biogas indicates the least NO emission at a fixed cocombustion ratio. Furthermore, reducing the furnace height at HGN = 17.3 m or titling down the burner at θBN = -15° contributed to a greater NO concentration at the furnace outlet.

19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(3): 266-272, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38538355

RESUMO

OBJECTIVE: To explore the value of cardiodynamicsgram (CDG) obtained from electrocardiogram (ECG) data by radial basis functionradial basis function (RBF) neural network in early diagnosis of patients with acute coronary syndrome (ACS). METHODS: Retrospective analysis method was used. Patients with chest pain as the main initial symptom in the emergency department of Baoan District People's Hospital of Shenzhen from October 2021 to September 2022 were enrolled. Baseline data were collected, including gender, age, smoking history, family history of coronary heart disease and history of hypertension, diabetes, hyperlipidemia, and atherosclerosis. The first 12-lead ECG was recorded after admission to the emergency department, and electrocardiodynamics analysis was performed to generate CDG. Receiver operator characteristic curve (ROC curve) was plotted to analyze the value of CDG and ECG in the early diagnosis of ACS and non-ST segment elevation ACS (NSTE-ACS). Sensitivity, specificity, area under the ROC curve (AUC), and 95% confidence interval (95%CI) were calculated. CDG and coronary angiography results of 3 patients with ACS with normal ECG were observed and analyzed. Non-ACS patients with normal ECG but positive CDG were followed for 30 days for adverse cardiovascular events. RESULTS: A total of 384 patients with chest pain were included, including 169 patients with ACS and 215 patients without ACS. The proportion of male (87.0% vs. 53.0%), smoking history (37.9% vs. 12.1%), hypertension (46.2% vs. 22.3%), diabetes (24.3% vs. 7.9%), hyperlipidemia (55.0% vs. 14.0%) and history of atherosclerosis (22.5% vs. 2.3%) in ACS group were significantly higher than those in non-ACS group (all P < 0.05). The ROC curve showed that the AUC of CDG diagnosis of ACS was higher than that of ECG [AUC (95%CI): 0.88 (0.66-0.76) vs. 0.71 (0.84-0.92)], the sensitivity was 92.8%, 78.6%, and the specificity was 83.3%, 64.2%, respectively. The AUC of CDG diagnosis of NSTE-ACS was higher than that of ECG [AUC (95%CI): 0.85 (0.80-0.90) vs. 0.63 (0.56-0.69)], the sensitivity was 87.1%, 61.3%, and the specificity was 83.3%, 64.2%, respectively. CDG of 3 patients with ACS with normal ECG showed disordered state, and coronary angiography showed ≥70% stenosis of major coronary branches. Of 215 non-ACS patients, 20 had a normal ECG but positive CDG, and 3 developed ST segment elevation myocardial infarction (STEMI) within 30 days, and 2 developed unstable angina (UA) within 30 days. CONCLUSIONS: CDG has high value in early diagnosis of ACS patients and is expected to become an important means of early diagnosis of ACS in emergency.


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Diabetes Mellitus , Hiperlipidemias , Hipertensão , Humanos , Masculino , Síndrome Coronariana Aguda/diagnóstico , Estudos Retrospectivos , Dor no Peito , Diagnóstico Precoce
20.
Crit Rev Oncol Hematol ; 193: 104226, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056580

RESUMO

Therapeutic approaches for cancer have become increasingly diverse in recent times. A comprehensive understanding of the tumor microenvironment (TME) holds great potential for enhancing the precision of tumor therapies. Neoadjuvant therapy offers the possibility of alleviating patient symptoms and improving overall quality of life. Additionally, it may facilitate the reduction of inoperable tumors and prevent potential preoperative micrometastases. Within the TME, cancer-associated fibroblasts (CAFs) play a prominent role as they generate various elements that contribute to tumor progression. Particularly, extracellular matrix (ECM) produced by CAFs prevents immune cell infiltration into the TME, hampers drug penetration, and diminishes therapeutic efficacy. Therefore, this review provides a summary of the heterogeneity and interactions of CAFs within the TME, with a specific focus on the influence of neoadjuvant therapy on the microenvironment, particularly CAFs. Finally, we propose several potential and promising therapeutic strategies targeting CAFs, which may efficiently eliminate CAFs to decrease stroma density and impair their functions.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias , Humanos , Terapia Neoadjuvante , Qualidade de Vida , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Fibroblastos
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