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1.
Mediators Inflamm ; 2020: 3560793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565723

RESUMO

In patients with chronic kidney disease, the abnormal activation of inflammatory pathways is usually an important factor leading to renal fibrosis and further deterioration of renal function. Finding effective intervention targets of the inflammatory signaling pathway is an important way to treat chronic kidney disease. As a newly discovered lysosomal membrane protein, the correlation between SID1 transmembrane family member 2 (Sidt2) and the inflammatory signaling pathway has not been reported. The aim of this study was to investigate the effect of Sidt2 on inflammation by inhibiting the expression of the Sidt2 gene in a mouse mesangial cell line mediated by a lentiviral CRISPR/Cas9 vector. Hematoxylin and eosin staining and microscopy found that the mesangial cells lost their normal morphology after inhibiting the expression of Sidt2, showing that the cell body became smaller, the edge between the cells was unclear, and part of the nucleus was pyknotic and fragmented, appearing blue-black. The expressions of IKK ß, p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the NF-κB pathway of the Sidt2 -/- group were higher than those of the Sidt2 +/+ group. p-Jak2 and IL6 increased in the Jak/Stat pathway, and p-ERK and p-P38 increased in the MAPK pathway. The expressions of IKK ß, p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the NF-κB pathway of the Sidt2 +/++LPS group were significantly higher than those in the Sidt2 +/+ group. The expressions of IKK ß, p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the Sidt2 -/-+LPS group were higher than those in the Sidt2 -/- group. The expressions of p-IKK α/ß, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the Sidt2 -/-+LPS group were higher than those in the Sidt2 +/++LPS group. In the Jak/Stat pathway, the protein expressions of p-Jak2 and IL6 in the Sidt2 +/++LPS group were higher than those in the Sidt2 +/+ group. The expressions of p-Jak2 and IL6 in the Sidt2 -/-+LPS group were higher than those in the Sidt2 -/- group. The expressions of p-Jak2 and IL6 in the Sidt2 -/-+LPS group were higher than those in the Sidt2 +/++LPS group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the MAPK pathway in the Sidt2 +/++LPS group were higher than those in the Sidt2 +/+ group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the Sidt2 -/-+LPS group were higher than those in the Sidt2 -/- group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the Sidt2 -/-+LPS group were higher than those in the Sidt2 +/++LPS group. These data suggested that deletion of the Sidt2 gene changed the three inflammatory signal pathways, eventually leading to the damage of glomerular mesangial cells in mice.

2.
Nano Lett ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32551705

RESUMO

Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. Utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumor and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs, and provides a promising strategy for improving cancer immunotherapy.

3.
J Clin Immunol ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514655

RESUMO

Haploinsufficiency of A20 (HA20) is a newly described immune dysregulation disease due to the loss-of-function mutation in TNFAIP3. In the present study, we report six patients from four unrelated Chinese families with distinct pathogenic mutations in TNFAIP3, including three novel variants. All of the patients presented with early-onset autoimmune/auto-inflammatory diseases, including Crohn's disease, Behcet's disease, systemic lupus erythematosus, and unclassified auto-inflammatory syndrome. Immunological phenotype tests showed elevated levels of serum pro-inflammatory cytokines, reduced naïve B cells and TFH cells, an inverted CD4:CD8 ratio, and increased susceptibility to restimulation-induced cell death (RICD) and FASL-induced apoptosis in derived T cells. Insufficient expression of A20 was found in these patients. A20 truncated protein was detected in mutant-transfected 293T cells. Upon TNF-α stimulation, the NF-κB pathway was over-activated in both derived T cells of these patients and mutant-transfected Hela cells. In conclusion, clinical manifestations are diverse in patients with HA20, even in those with the same TNFAIP3 mutation. A20 inhibits the NF-κB pathway and plays a crucial role in the regulation of cell death. Haploinsufficiency of A20 leads to defects in both innate and adaptive immunity.

4.
Neurochem Res ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488470

RESUMO

Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1ß, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.

5.
Travel Med Infect Dis ; : 101782, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32526372

RESUMO

INTRODUCTION: There are currently no satisfactory methods for predicting the outcome of Coronavirus Disease-2019 (COVID-19). The aim of this study is to establish a model for predicting the prognosis of the disease. METHODS: The laboratory results were collected from 54 deceased COVID-19 patients on admission and before death. Another 54 recovered COVID-19 patients were enrolled as control cases. RESULTS: Many laboratory indicators, such as neutrophils, AST, γ-GT, ALP, LDH, NT-proBNP, Hs-cTnT, PT, APTT, D-dimer, IL-2R, IL-6, IL-8, IL-10, TNF-α, CRP, ferritin and procalcitonin, were all significantly increased in deceased patients compared with recovered patients on admission. In contrast, other indicators such as lymphocytes, platelets, total protein and albumin were significantly decreased in deceased patients on admission. Some indicators such as neutrophils and procalcitonin, others such as lymphocytes and platelets, continuously increased or decreased from admission to death in deceased patients respectively. Using these indicators alone had moderate performance in differentiating between recovered and deceased COVID-19 patients. A model based on combination of four indicators (P = 1/[1 + e-(-2.658+0.587×neutrophils - 2.087×lymphocytes - 0.01×platelets+0.004×IL-2R)]) showed good performance in predicting the death of COVID-19 patients. When cutoff value of 0.572 was used, the sensitivity and specificity of the prediction model were 90.74% and 94.44%, respectively. CONCLUSIONS: Using the current indicators alone is of modest value in differentiating between recovered and deceased COVID-19 patients. A prediction model based on combination of neutrophils, lymphocytes, platelets and IL-2R shows good performance in predicting the outcome of COVID-19.

6.
Surg Endosc ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32500459

RESUMO

BACKGROUND: Anatomical liver resection is an established procedure for primary hepatic tumors. Laparoscopic anatomical hepatectomy has been proven to be technically achievable from S1 to S8 in experienced hands. The indocyanine green (ICG) fluorescence imaging technique offers a novel tool of intraoperative visualization in hepatobiliary surgery. This study aims to investigate the feasibility of laparoscopic anatomical liver resection based on segmental staining using real-time ICG fluorescence. METHODS: From December 2015 to October 2017, 36 patients in our institute underwent lap-ALR using real-time ICG fluorescence mapping of the tumor-bearing portal territory. The procedural and perioperative data were collected and analyzed. RESULTS: In our case series, we successfully performed the fashion of positive staining mostly in segmentectomy or sub-segmentectomy by individually injecting 5-10 ml of ICG (0.025 mg/ml) into its feeding portal branch guided by intraoperative ultrasound, and the negative staining mainly for sectionectomy, hemihepatectomy and multi-segmentectomy by interrupting the Glissonean pedicle serving the tumor-bearing segments and systemically injecting 1 ml of ICG (2.5 mg/ml). Our total successful rate of staining is 53%. No conversion to laparotomy, Clavien III-IV complication or 90-day mortality occurred. Valuable technical feedback, experience and lessons are learned from this initial practice. CONCLUSIONS: Real-time ICG fluorescence imaging adds much precision to laparoscopic anatomical hepatectomy. The success of segmental staining requires a high proficiency of IOUS and skillful interpretation of preoperative 3D simulation. Decision-making on the fashions of positive and negative staining have been initially recommended. Multi-centered practice and technical modification are necessary to standardize its application.

7.
Int J Infect Dis ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497795

RESUMO

BACKGROUND: Discriminating active tuberculosis (ATB) from latent tuberculosis infection (LTBI) remains challenging. The aim of this study was to investigate a diagnostic model based on the combination of iron metabolism and TB-specific antigen/phytohemagglutinin ratio (TBAg/PHA ratio) in T-SPOT.TB assay for differentiation between ATB and LTBI. METHODS: A total of 345 participants with ATB (n = 191) and LTBI (n = 154) were recruited based on positive T-SPOT.TB results at Tongji hospital between January 2017 and January 2020. Iron metabolism analysis was performed simultaneously. Diagnostic model for distinguishing ATB from LTBI was established according to multivariate logistic regression. RESULTS: TBAg/PHA ratio showed 64.00% sensitivity and 90.10% specificity in distinguishing ATB from LTBI when a threshold of 0.22 was used. All iron metabolism biomarkers in ATB group were significantly different from those in LTBI group. Specifically, serum ferritin and soluble transferrin receptor in ATB were significantly higher than LTBI. On the contrary, serum iron, transferrin, total iron binding capacity, and unsaturated iron binding capacity in ATB were significantly lower than LTBI. The combination of iron metabolism indicators accurately predicted 60.00% of ATB cases and 91.09% of LTBI subjects, respectively. Moreover, the combination of iron metabolism indexes and TBAg/PHA ratio resulted in a sensitivity of 88.80% and specificity of 90.10%, respectively. Furthermore, the performance of models established in Qiaokou cohort was confirmed in Caidian cohort. CONCLUSIONS: Our data suggest that the combination of iron metabolism indexes and TBAg/PHA ratio could serve as a biomarker to distinguish ATB from LTBI in T-SPOT-positive individuals.

8.
Life Sci ; : 117889, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32502541

RESUMO

PURPOSE: Gestational diabetes mellitus (GDM) has many adverse effects on offspring, such as abnormal glycolipid metabolism, obesity, insulin resistance, mental retardation, schizophrenia and so on. METHODS: We established a GDM rat model by injecting 1% streptozotocin associated with a high-fat diet one week before pregnancy, and offspring rats were sacrificed at 8 weeks of age to obtain liver tissue for study. We used hematoxylin-eosin (HE) staining to observe liver morphological changes, Tunel staining for hepatocyte apoptosis, transmission electron microscope for liver ultrastructure, and western blot for protein expression in liver tissue. RESULTS: Compared with normal offspring rats, hepatocytes of GDM offspring rats showed obvious edema, liver organ index increased, and hepatocyte apoptosis and autophagosome in the liver were significantly increased; Bax, cleaved-caspase3/caspase3, LCII, Beclin 1, P-IKBα/IKBα and P-p65/p6 protein expression in the liver were significantly increased; Bcl2, p62 and PPARγ protein expression in the liver were significantly decreased. Tau prevented the GDM-related effects in the offspring: Tau decreased hepatocyte edema (or even disappears), liver organ index, hepatocyte apoptosis and the number of autophagosomes in the liver. In addition, Tau also decreased Bax, cleaved-caspase3/caspase3, LCII, Beclin 1, P-IKBα/IKBα and P-p65/p6 protein expression, and increased Bcl2, p62 and PPARγ protein expression in the liver of GDM offspring rats. CONCLUSION: Taurine should be considered as a potential gestational nutritional supplement to prevent liver damage in GDM offspring.

9.
Tuberculosis (Edinb) ; 122: 101941, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32501259

RESUMO

BACKGROUND: Diagnosing tuberculous pleurisy (TP) remains a clinical challenge and the best method to diagnose it is controversial. Although several studies have investigated the performance of pleural fluid (PF) T-SPOT for pleural tuberculosis (plTB) diagnosis, the heterogeneity of its accuracy exists. Therefore, we performed an updated meta-analysis of the existing evidence on the utility of PF T-SPOT to diagnose TP. METHODS: PubMed and EmBase were searched for relevant English articles up to July 29, 2019. Statistical analysis was performed using Stata, Revman, and Meta-Disc. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic (SROC) curves and the area under the curve (AUC) were used to summarize the overall diagnostic performance. RESULTS: A total of 13 studies (997 patients with TP and 656 patients without TP) were identified and enrolled to meta-analysis, giving the following pooled values for diagnostic accuracy of PF T-SPOT: sensitivity, 0.91 (95% CI, 0.89-0.92, I2 = 80.9%); specificity, 0.88 (95% CI, 0.86-0.91, I2 = 87.3%); PLR, 6.28 (95% CI, 2.88-13.69, I2 = 93.3%); NLR, 0.12 (95% CI, 0.07-0.21, I2 = 84.9%); DOR, 59.74 (95% CI, 24.13-147.93, I2 = 78.3%); and the area under the SROC curve, 0.95 (95% CI, 0.93-0.97). CONCLUSIONS: Our meta-analysis suggests that PF T-SPOT has important diagnostic value for plTB. However, the standardization of the operating procedure needs to be further promoted, which would make the results more credible.

10.
Sci Total Environ ; 739: 139622, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32535458

RESUMO

Land cover change (LCC) is a major part of environmental change. Exploring the spatiotemporal differences in LCC and the driving factors is the basis for comprehensive research on landscape planning, and it is of great significance for future effective and sustainable landscape management. In this respect, cross-scale research with integrated methods is worthy of more attention, although some studies have discussed the driving forces of LCCs at either regional or local scale. We combined a structural equation model and a mixed-effects model for quantifying the driving forces of LCCs across different scales in the Loess Plateau (China), which is a typical region that has experienced significant LCCs over recent decades. The impacts of biophysical and socioeconomic factors on different change trajectories (agricultural intensification, urbanization and ecological restoration) were found to be inconsistent at different temporal and spatial scales. We found that topography had a negative effect on agricultural intensification during 1990-2010 and on urbanization during 1990-2000, but it had a positive effect on ecological restoration during 2000-2015 at the regional scale. Moreover, although there was no significant impact from economic development on any type of LCCs at the regional scale, its important influence could be seen in some of the township categories. Therefore, the path and scale dependence of driving forces is an important consideration in landscape planning and management to accommodate local conditions and fine-tuned analysis as decision-making supports.

11.
Biosens Bioelectron ; 162: 112261, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32392160

RESUMO

Cancer cells alter their metabolism to promote rapid proliferation, resulting in significant amounts of glucose to be used for aerobic glycolysis in the tumor microenvironment. Due to the spatial mismatch between electrodes and cells, existing methods for evaluating cancer cell metabolism lack kinetic and microenvironmental information. In this paper, we present a hollow fiber structure loaded with sensing elements as a long-term cellular metabolism monitoring platform. The unique gradient porous structure allowed the glucose sensor to be close to cultured cells but not directly in contact to prevent adverse effects. The liquid exchange channels in the porous fiber structure ensured continuous and real-time monitoring of glucose concentration changes in the culture media. Experimental results showed high electrochemical sensitivity and stability for continuously monitoring the glucose consumption rate. Furthermore, a continuous three-day long test quantified the change in glucose consumption in response to the anticancer drug Osimertinib. In addition to traditional endpoint cell counting and analysis, this hollow fiber sensing structure provided a real-time monitoring tool for cell metabolism. Such continuous monitoring of the cell metabolism microenvironment improves in-vitro toxicology models for personalized medicine and cancer therapy.

12.
Aging (Albany NY) ; 12(10): 9328-9343, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396527

RESUMO

BACKGROUND: Quantitatively assessing host immunity remains a challenge in clinical practice. RESULTS: Most parameters in lymphocyte number, function and phenotype were correlated with age. The reference ranges of these parameters were established in four age groups (children, adolescents, adults, and elders). The numbers of CD4+ T cells, CD8+ T cells, B cells, but not NK cells, were negatively correlated with age. However, the function of CD4+ T cells, CD8+ T cells and NK cells was positively correlated with age. The expression of CD28 on T cells gradually decreased with increasing age and was negatively correlated with their function. An opposite phenomenon was observed in the expressions of HLA-DR and CD45RO on T cells. An immune scoring model was established by using 8 parameters (CD4+ T cell number × function, CD28+CD4+ T cell number, HLA-DR+CD4+ T cell number, CD45RO+CD4+ T cell number, CD8+ T cell number × function, CD28+CD8+ T cell number, HLA-DR+CD8+ T cell number, NK cell number × function) from the results of lymphocyte number, function, and phenotype. This immune scoring model showed sensitivities of 70% and 71.4% in determining hyper-immune and hypo-immune status, respectively. CONCLUSIONS: An immune scoring model based on combination of lymphocyte number, function, and phenotype shows potential value in quantitatively assessing host immunity. METHODS: 261 healthy individuals aged 1 to 82 years were recruited from Tongji Hospital. The number, function, and phenotype of CD4+ T cells, CD8+ T cells and NK cells were simultaneously determined.

13.
Horm Metab Res ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375182

RESUMO

Although glucagon-like peptide-1 (GLP-1) analogue has been reported to suppress oxidative stress in non-alcoholic fatty liver disease (NAFLD), an effective therapeutic agent for NAFLD is currently unavailable. Therefore, in this study, we aimed to investigate the protective effects of the GLP-1 analogue liraglutide against lipotoxicity-induced oxidative stress in HepG2 cells and to elucidate the underlying mechanisms. HepG2 cells were cultured for 48 hours and treated with a free fatty acid (FFA) mixture: FFA mixture and liraglutide or FFA mixture, liraglutide, and exendin (9-39). Lipid accumulation was examined by oil red O staining. Oxidative stress was assessed by measuring the levels of intracellular reactive oxygen species using 2',7'-dichlorofluorescein diacetate and thiobarbituric acid-reactive substances, whereas antioxidant capacity was assessed by measuring the activity of superoxide dismutase and catalase. Expression of the nuclear factor erythroid-2-related factor 2 (NRF2) gene and the genes encoding antioxidant enzymes was analyzed using quantitative RT-PCR. Cellular and nuclear NRF2 expression levels were assessed using immunofluorescence cell staining and western blotting. Liraglutide treatment reduced high fat-induced lipid formation and the levels of oxidative stress markers and increased antioxidant enzyme activity in HepG2 cells. Liraglutide treatment increased the mRNA expression of NRF2 target genes, induced NRF2 nuclear translocation, and increased nuclear NRF2 levels without altering NRF2 mRNA expression. Collectively, these results indicate that liraglutide exhibits a protective effect against lipotoxicity-induced oxidative stress, possibly via modulation of NRF2 and expression of antioxidant enzymes in liver cells.

15.
Biomed Res Int ; 2020: 5059079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32461994

RESUMO

Objectives: To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods: We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I 2 statistics. The main outcome measure was overall survival (OS). Results: After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT-treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P < 0.05). Notably, there were higher odds of high-grade (grade ≥ 3) adverse events with IOCT (RR: 1.81, 95% CI: 1.13-2.90), but the risk of treatment-related death (RR: 1.16, 95% CI: 0.84-1.60) was not increased compared with non-IOCT. Conclusions: IOCT is a preferable treatment option over PD-1/PD-L1 inhibitor monotherapy and conventional therapy for patients with advanced solid tumors. However, we should note the increased incidence rate of high-grade AEs in IOCT.

16.
Int J Infect Dis ; 95: 436-440, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371192

RESUMO

BACKGROUND: The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice. METHODS: Between January 2018 and March 2020, 1,027 NCPP and 1,140 IP were recruited from Tongji hospital. Routine blood examination, biochemical indicators and coagulation function analysis were simultaneously performed in all participants. RESULTS: There was no sex predominance in NCPP. The NCPP were frequently encountered in the sixth and seventh decades of life. The mean age of NCPP (56±16 years) was higher than IP (47±17 years), but without statistical difference. Although most results of routine laboratory tests between NCPP and IP had no significant differences, some laboratory tests showed an obvious change in NCPP. It was observed that NCPP had significantly decreased white blood cells, alkaline phosphatase and d-dimer compared with IP. However, the results of lactate dehydrogenase, erythrocyte sedimentation rate and fibrinogen were significantly increased in NCPP compared with IP. The diagnostic model based on a combination of 18 routine laboratory indicators showed an area under the curve of 0.796 (95% CI, 0.777-0.814), with a sensitivity of 46.93% and specificity of 90.09% when using a cut-off value of 0.598. CONCLUSIONS: Some routine laboratory results had statistical difference between NCPP and IP. A diagnostic model based on a combination of routine laboratory results provided an adjunct approach in the differential diagnosis between NCPP and IP.

17.
BMC Plant Biol ; 20(1): 200, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32384927

RESUMO

BACKGROUND: The interactions between Growth-regulating factors (GRFs) and GRF-Interacting Factors (GIFs) have been well demonstrated but it remains unclear whether different combinations of GRF and GIF play distinctive roles in the pathway downstream of the complex. RESULTS: Here we showed that OsGRF1 and OsGIF1 synergistically regulate leaf growth in rice. The expression of OsGIF1 emerged in all tissues with much higher level while that of OsGRF1 appeared preferentially only in the stem tips containing shoot apical meristem (SAM) and younger leaves containing leaf primordium. Overexpression of an OsmiR396-resistant version of mOsGRF1 resulted in expanded leaves due to increased cell proliferation while knockdown of OsGRF1 displayed an opposite phenotype. Overexpression of OsGIF1 did not exhibit new phenotype while knockdown lines displayed pleiotropic growth defects including shrunken leaves. The crossed lines of mOsGRF1 overexpression and OsGIF1 knockdown still exhibited shrunk leaves, indicating that OsGIF1 is indispensable in leaf growth regulated by OsGRF1. The expression of OsGRF1 could be upregulated by gibberellins (GAs) and downregulated by various stresses while that of OsGIF1 could not. CONCLUSION: Our results suggest that OsGIF1 is in an excessive expression in various tissues and play roles in various aspects of growth while OsGRF1 may specifically involve in leaf growth through titrating OsGIF1. Both internal and external conditions impacting leaf growth are likely via way of regulating the expression of OsGRF1.

18.
J Infect ; 81(1): 81-89, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32360883

RESUMO

OBJECTIVES: Distinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging. METHODS: The modified T-SPOT.TB assay was performed in 499 participants (243 ATB and 256 LTBI) and another 322 participants (162 ATB and 160 LTBI) who were diagnosed in Qiaokou (training) and Caidian (validation) cohort respectively. RESULTS: The mean spot sizes (MSS) of early secreted antigenic target 6 (ESAT-6) spot-forming cells (SFC) of T-SPOT.TB assay in ATB patients was significantly higher than that in LTBI individuals. 1.0 × 105 was the optimal number of cells added to phytohaemagglutinin (PHA) well for obtaining more accurate TB-specific antigen to phytohaemagglutinin (TBAg/PHA) ratio. The area under the curve of the diagnostic model by combination of ESAT-6 SFC MSS and modified TBAg/PHA ratio in distinguishing ATB from LTBI was 0.959 in training cohort, with a sensitivity of 90.12% and a specificity of 91.02% when a cutoff value of 0.46 was used. This diagnostic model showed similar performance in the validation cohort. The area under the curve, sensitivity, and specificity were 0.962, 93.21%, and 90.00%, respectively. Further flow cytometry analysis showed that ESAT-6 stimulation induced a significantly higher mean fluorescence intensity of IFN-γ+ cells in lymphocytes compared with culture filtrate protein 10 (CFP-10) stimulation. In contrast, CFP-10 stimulation induced a significantly higher percentage of IFN-γ+ cells in lymphocytes compared with ESAT-6 stimulation. CONCLUSIONS: The combination of the MSS of ESAT-6 SFC and the modified TBAg/PHA ratio of T-SPOT.TB assay showed great value in discriminating ATB from LTBI.

19.
Molecules ; 25(8)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316307

RESUMO

A two-step process was proposed to enhance enzymatic hydrolysis of Miscanthus sinensis based on a comparative study of acid/alkaline pretreatments. Ferric chloride pretreatment (FP) effectively removed hemicellulose and recovered soluble sugars, but the enzymatic hydrolysis was not efficient. Dilute alkaline pretreatment (ALP) resulted in much better delignification and stronger morphological changes of the sample, making it more accessible to enzymes. While ALP obtained the highest sugar yield during enzymatic hydrolysis, the soluble sugar recovery from the pretreatment stage was still limited. Furthermore, a two-step ferric chloride and dilute alkaline pretreatment (F-ALP) has been successfully developed by effectively recovering soluble sugars in the first FP step and further removing lignin of the FP sample in the second ALP step to improve its enzymatic hydrolysis. As a result, the two-step process yielded the highest total sugar recovery (418.8 mg/g raw stalk) through the whole process.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32282952

RESUMO

A homogeneous monomeric laccase (ASL) from Agaricus sinodeliciosus, with a molecular mass of 65 kDa, was isolated using ion-exchange chromatography (CM-cellulose and Q-Sepharose) and gel-filtration chromatography (Superdex 75). This laccase exhibited maximum activity at 50 °C and pH 5.0. Hg2+ and Cd2+ significantly inhibited its activity. The laccase displayed a Km value of 0.9 mM toward 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS). In addition to ABTS, ASL exhibited higher affinity toward o-toluidine and benzidine than other substrates. ASL is able to decolorize malachite green and Eriochrome black T.

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