يعرض 1 - 10 نتائج من 12 نتيجة بحث عن '"Junfang Zhou"', وقت الاستعلام: 1.16s تنقيح النتائج
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    المصدر: International Journal of Biological Macromolecules. 193:2173-2182

    الوصف: Although class B scavenger receptors (SR-Bs) in mammals are multifunctional molecules, the functions of SR-Bs in invertebrates remain largely unknown. In this study, we characterized an SR-B homolog, namely SpSR-B2, from Scylla paramamosain. SpSR-B2 shared high similarity with mammalian SR-Bs, and exhibited specific binding activity to ac-LDL, indicating that it may be a new member of SR-B class in invertebrates. SpSR-B2 was upregulated after challenge with white spot syndrome virus (WSSV) or bacteria. Binding assays showed that SpSR-B2 specifically interacted with WSSV envelope protein VP24. Besides, SpSR-B2 could bind to all tested bacterial cells and agglutinate these bacteria. SpSR-B2 also exhibited a strong binding activity to LPS but weak binding activities to other tested polysaccharides. These findings indicated that SpSR-B2 was a potential recognition molecule for viral protein VP24 and bacterial LPS. Knockdown of SpSR-B2 resulted in dramatically decreased expressions of certain antimicrobial peptides (AMPs), and overexpression of SpSR-B2 led to the increased expression of the AMP of SpALF2, suggesting that SpSR-B2 could regulate the expression of AMPs. Taken together, this study revealed that SpSR-B2 functioned as a potential pattern recognition receptor participating in antiviral and antibacterial immunity, and provided new insights into the immune functions of invertebrate SR-Bs.

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    المصدر: Journal of environmental management. 321

    الوصف: Rapid urbanization has altered landscape patterns and ecological functions, causing a decline in ecosystem service and generating many ecological and environmental issues. Studying the spatiotemporal interaction between urbanization and ecosystem service (ES) can provide effective supports for regional sustainability and policy formulation. This research utilizes the Yangtze River Economic Belt (YREB) as a case to analyze the spatiotemporal interaction between multi-urbanization indicators and multi-ESs over a large-scale region. The results show that the urbanization process in the YREB evolves from a rapidly growing state to a steady state with a slower rise. The urbanization level of the Yangtze River Delta urban agglomeration is relatively higher than the other regions. The distribution pattern of urbanization shows an overall characteristic of lower urbanization in the west and higher in the east. From 2009 to 2016, ecosystem service value (ESV) in the YREB decreased first and then increased, ESV in 2016 showed a reduction of 12.768 billion yuan compared with the 2009 level. ESV increases gradually from highly urbanized areas to those with lower levels of urbanization. Areas with high ESV levels are distributed at the middle reaches of YREB. There is a U-shaped curve relationship between urbanization and ESV, the ESV sharply increased when the urbanization index exceeded 0.6 in 2012. Land urbanization has the greatest impact on ESV among the four subtypes of urbanization indicators. Urbanization and ESV show the synergy relationship mostly in the eastern region, accounting for 18.18% of the total 110 cities. By contrast, they present the trade-off relationship in northern, southern and central regions, occupying 47.27% of the total observations. This study is helpful to provide scientific suggestions regarding the development of new urbanization, the protection of ESV, and the issue of how to achieve synergistic and sustainable development between them.

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    المصدر: Fish & Shellfish Immunology. 36:172-180

    الوصف: Anti-lipopolysaccharide factors (ALFs) are antimicrobial peptides with binding and neutralizing activities to lipopolysaccharide (LPS) in crustaceans. This study identified and characterized a novel ALF homolog (SpALF4) from the mud crab Scylla paramamosain. The complete cDNA of SpALF4 had 756 bp with a 381 bp open reading frame encoding a protein with 126 aa. The deduced protein contained a signal peptide and a LPS-binding domain. SpALF4 shared the highest identity with PtALF5 at amino acid level but exhibited low similarity with most of other crustacean ALFs. Furthermore, different from the previously identified three SpALF homologs and most of other ALFs, SpALF4 had a low isoelectric point (pI) for the mature peptide and the LPS-binding domain with the values of 6.93 and 6.74, respectively. These results indicate that SpALF4 may be a unique ALF homolog with special biological function in the mud crab. Similar to the spatial structure of ALFPm3, SpALF4 contains three α-helices packed against a four-strand β-sheet, and an amphipathic loop formed by a disulphide bond between two conserved cysteine residues in LPS-binding domain. SpALF4, mainly distributed in hemocytes, could be upregulated by Vibrio harveyi, Staphylococcus aureus, or white spot syndrome virus. Recombinant SpALF4 could inhibit the growth of Gram-negative bacteria (V. harveyi, Vibrio anguillarum, Vibrio alginolyticus, Aeromonas hydrophila, Pseudomonas putida), Gram-positive bacteria (S. aureus and Bacillus megaterium), and a fungus Candida albicans to varying degrees. Further study showed that it could also bind to all the aforementioned microorganisms except S. aureus. These results demonstrate that SpALF4 is a unique ALF homolog with potent antimicrobial activity against bacteria and fungi. This characteristic suggests SpALF4 plays an essential function in immune defense against pathogen invasion in mud crab.

  4. 4

    المصدر: Environmental toxicology and pharmacology. 46

    الوصف: In this study with crucian carp (Carassius auratus gibelio), the effect on enrofloxacin (EF) and its metabolite ciprofloxacin (CF) and on the activity of cytochrome P450 1A (CYP1A) and cytochrome P450 3A (CYP3A) was estimated following the oral administration of rifampicin (RIF) (12mg/kg) and β-naphthoflavone (BNF) (12mg/kg), respectively. First, reversed-phase high-performance liquid chromatography (RP-HPLC) was used to detect the pharmacokinetics of EF with continual blood sampling. In RIF-treated, BNF-treated and control groups, the value of the CmaxCF/CmaxEF ratio was 4.41, 0.81 and 0.95, and the corresponding value of the AUC0-t-CF/AUC0-t-EF ratio was 3.69, 1.84 and 1.76, respectively. In the RIF-treated, BNF-treated and control groups, the MRT values of EF were 26.57, 27.45 and 30.88h, and the corresponding values for CF were 5.79, 35.18 and 38.11h, respectively. Based on these results for crucian carp, the accumulation and elimination of EF and CF in the RIF-treated group were more rapid than in BNF-treated and control groups. Second, liver microsomes were pretreated with the inducer of CYP1A for BNF and that of CYP3A for RIF, and then the enzymatic activities of CYP1A and CYP3A were measured, respectively. The activities of ethoxyresorufin-O-deethylation (EROD) and erythromycin-N-demethylation (ERND) increased significantly (P

  5. 5

    المصدر: Journal of Pediatric Surgery. 42:1172-1179

    الوصف: Background We evaluated the potential of bioluminescence imaging (BLI) for early tumor detection, demonstrating occult sites of disseminated disease and assessing disease progression in a murine model of neuroblastoma. Methods Neuroblastoma cells engineered to express the enzyme firefly luciferase were used to establish localized tumors and disseminated disease in SCID mice. Bioluminescent signal intensity was measured at serial time points, and compared with traditional methods of evaluating tumor growth. Results Bioluminescence imaging detected subcutaneous and retroperitoneal tumors weeks before they were palpable or appreciable by ultrasound. Bioluminescent signal intensity at both sites then paralleled tumor growth. After intravenous administration of tumor cells, BLI revealed disseminated disease in the liver, lungs, and bone marrow, again weeks before any gross disease was present. The presence of tumor within these sites at early time points was confirmed by reverse transcriptase–polymerase chain reaction. Finally, BLI permitted a real-time, noninvasive, quantitative method for following response to therapy in a model of minimal residual disease. Conclusion Bioluminescence imaging detects tumor much earlier than traditional methods. In addition, it can detect, quantify, and follow micrometastasis in real-time during disease progression. This methodology is extremely valuable for studying tumor tissue tropism, mechanisms of metastasis, and response to therapy in murine tumor models.

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    المساهمون: REPSOL, Madrid, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Immunologie moléculaire et biothérapies innovantes (IMBI), Généthon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Évry-Val-d'Essonne (UEVE)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Department of Mathematics [Berkeley], University of California [Berkeley], University of California-University of California, University of Oklahoma (OU), University of Salford, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC)

    المصدر: N Engl J Med
    N Engl J Med, 2014, 371 (21), pp.1994-2004. ⟨10.1056/NEJMoa1407309⟩

    الوصف: International audience; BACKGROUND: In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity. METHODS: We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2x10(12) vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. RESULTS: A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (+/-SD) of 5.1+/-1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. CONCLUSIONS: In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238.).

  7. 7

    المصدر: Journal of Pediatric Surgery. 40:236-243

    الوصف: Purpose The purpose of this study was to evaluate the ability of adeno-associated virus (AAV) vector-mediated delivery of pigment epithelium-derived factor (PEDF) to inhibit neuroblastoma (NB) xenograft growth. Pigment epithelium-derived factor was chosen for this study because, in addition to being a potent inhibitor of angiogenesis, it is capable of inducing neuronal differentiation. Methods Cohorts of mice received either recombinant AAV encoding human PEDF (rAAV-hPEDF) at a range of doses or control vector via tail vein. Subsequent hPEDF expression was measured by enzyme-linked immunoassay. After 6 weeks, the mice were given human NB cells by retroperitoneal injection and then killed 5 weeks later. Tumor weight, microvessel density, tumor differentiation, apoptosis, and levels of intratumoral vascular endothelial growth factor (VEGF) expression were determined at that time. In subsequent cohorts of mice, AAV-mediated murine PEDF expression was tested against both human NB xenografts and murine tumors. Results In a series of in vitro studies, PEDF was shown to inhibit endothelial cell activation and to stimulate differentiation of NB cell lines. After tail vein injection of rAAV-hPEDF, stable transgene expression was generated and correlated with levels of vector administration. Human NB xenograft growth was restricted by hPEDF in a dose-dependent fashion. Intratumoral VEGF expression and microvessel density were decreased, and tumor cell apoptosis was increased in PEDF-treated mice. Conclusions Treatment with PEDF had a significant impact on NB growth in mice when delivered continuously using a gene therapy–mediated approach. The activity of PEDF appears to be mediated in part by inhibition of tumor-induced angiogenesis through down-regulation of tumor-elaborated VEGF, with subsequent intratumoral apoptosis. Furthermore, hPEDF was able to induce NB differentiation in vitro and in vivo. In addition, antitumor efficacy was seen when mouse PEDF was used to treat syngeneic murine tumors. In our murine models, gene therapy–mediated delivery of PEDF appears promising for the treatment of neuroblastoma.

  8. 8

    المصدر: Molecular biology reports. 40(12)

    الوصف: Peroxinectin (PX) with cell adhesion and peroxidase activities is important in invertebrate immune responses. We identified a novel PX homolog from Scylla paramamosain (designated as Sp-PX) through transcriptome sequencing. The full-length of cDNA sequence was 3,165 bp. And there was a peroxidase domain in the deduced protein sequence. A cell-adhesive sequence (KGD motif) was also found in the N-terminus. The predicted molecular mass of the mature protein is 83.9 kDa, with an estimated pI of 6.21. At the amino acid level, Sp-PX shared much higher similarities with other crustaceans PX proteins. And Sp-PX also exhibited some similarities with other peroxidase family members. According to real-time polymerase chain reaction, Sp-PX was mainly distributed in the hemocytes. The gene expression levels in the hemocytes of the normal and white spot syndrome virus (WSSV)-challenged crabs were compared via high-throughput RNA sequencing technology, and the results showed that Sp-PX was upregulated at 48 h post-WSSV challenge. Subsequently, how Sp-PX responds to WSSV stimulus was explored through time-course experiments. The Sp-PX transcripts dramatically increased and reached the highest level at 12 h post-injection, whereas Sp-PX transcripts were recovered at 96 h post-challenge. Meanwhile, it was found that the WSSV copies proliferated significantly after a period of latent viral infection for 48 h. In addition,Sp-PX transcripts were also upregulated after Vibrio harveyi or Staphylococcus aureus challenge. Overall, Sp-PX not only participates in antibacterial immunity but also plays a crucial role in the antiviral immune responses of mud crab at the early stage of WSSV infection.

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    الوصف: Purpose Rapamycin inhibits vascular endothelial growth factor expression. Vascular endothelial growth factor is a tumor-elaborated protein that stimulates neovascularization. This inhibition can cause transient "normalization" of the generally dysfunctional tumor vasculature, resulting in improved tumor perfusion and oxygenation. We hypothesized that this may potentiate the antitumor effects of adjuvant ionizing radiation. Methods Mice bearing orthotopic Rh30 alveolar rhabdomyosarcomas were treated with rapamycin (5 mg/kg intraperitoneally daily ×5). Tumors were then evaluated for changes in intratumoral oxygenation, perfusion, vessel permeability, and microvessel density. Additional tumor-bearing mice were treated with 5 doses of rapamycin, irradiation (4 Gy), or 5 doses of rapamycin with irradiation administered on the first or sixth day of rapamycin treatment. Results Although tumor vessel permeability changed only minimally, microvessel density decreased (3153 ± 932 vs 20,477 ± 3717.9 pixels per high-power field), whereas intratumoral oxygenation increased significantly (0.0385 ± 0.0141 vs 0.0043 ± 0.0023 mm Hg/mm 3 ) after 5 doses of rapamycin. Contrast-enhanced ultrasound demonstrated a significantly increased rate of change of signal intensity after 5 days of rapamycin, suggesting improved intratumoral perfusion. Tumor volume 14 days after treatment was smallest in mice treated with the combination of rapamycin given before irradiation. Conclusion Combination therapy with rapamycin given before irradiation to normalize the tumor vasculature, thereby improving tumor oxygenation, increased the sensitivity of alveolar rhabdomyosarcoma xenografts to adjuvant irradiation.

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    الوصف: Background Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. Methods We infused a single dose of a serotype-8–pseudotyped, self-complementary adeno virus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity