366 research outputs found

    Characterization of subcellular localization of duck enteritis virus UL51 protein

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    <p>Abstract</p> <p>Background</p> <p>Knowledge of the subcellular localization of a protein can provide useful insights about its function. While the subcellular localization of many alphaherpesvirus UL51 proteins has been well characterized, little is known about where duck enteritis virus (DEV) UL51 protein (pUL51) is targeted to. Thus, in this study, we investigated the subcellular localization and distribution of DEV pUL51 by computer aided analysis, as well as indirect immunofluorescence (IIF) and transmission immunoelectron microscopy (TIEM) approaches in DEV-infected cells.</p> <p>Results</p> <p>The DEV UL51 gene product was identified as an approximate 34 kDa protein in DEV-infected cells analyzed by western blotting. Computer aided analysis suggested that DEV pUL51 is not targeted to the mitochondrial, extra-cellular or nucleus, but be targeted to the cytoplasmic in host cells, more specifically, palmitoylation of the pUL51 through the N-terminal cysteine at position 9 makes membrane association and Golgi localization possible. Using IIF analysis, we found that DEV pUL51 was first detected in a juxtanuclear region of DEV-infected cells at 9 h postinfection (p.i.), and then was detected widely distributed in the cytoplasm and especially was stronger in the juxtanuclear region from 12 to 60 h p.i. TIEM analysis revealed that DEV pUL51 was mainly associated with cytoplasmic virions and also with some membranous structure near the pUL51-specific immuno-labeling intracellular virion in the cytoplasmic vesicles; moreover, the pUL51 efficiently accumulated in the Golgi apparatus at first, and then was sent to the plasma membrane from the Golgi by some unknown mechanism.</p> <p>Conclusion</p> <p>In this work, we described the basic characteristics of pUL51 subcellular localization and distribution for the first time. From these results, we concluded that palmitoylation at the N-terminal cysteine, which is conserved in all alphaherpesvirus UL51 homologs, is required for its membrane association and Golgi localization, and the pUL51 mainly localized to the juxtanuclear region of DEV-infected cells, as well seemed to be incorporated into mature virions as a component of the tegument. The research will provide useful clues for DEV pUL51 functional analysis, and will be usefull for further understanding the localization properties of alphaherpesvirus UL51 homologs.</p

    Characterization and genomic analysis of Bacillus megaterium with the ability to degrade aflatoxin B1

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    Coix seed is a good product for both medicinal and food use, which is highly susceptible to aflatoxin B1 (AFB1) contamination during field transport, storage, and processing. The aim of this study is to find microbial strains that can solve the problem of contamination of coix seed. In this study, the AFB1-degrading microorganism SX1-1 was isolated and identified as a Bacillus megaterium based on morphology, microscopy, and 16S rDNA sequencing. The optimum culture conditions for SX1-1 to degrade AFB1 were determined to be 12 h. The optimum degradation conditions were 72 h, 57°C, and an initial pH of 8.0. The highest degradation of AFB1 was observed in the fermentation supernatant of the SX1-1 strain, with a degradation rate of 97.45%. In addition, whole-genome sequencing analysis of this strain revealed the presence of a number of enzymes that could potentially degrade AFB1. Importantly, SX1-1 was able to degrade AFB1-contaminated coix seed in situ by 50.06% after co-culture. In conclusion, this strain had a high AFB1 degradation ability, and has great potential and great application as a biocontrol agent for AFB1 degradation of coix seed

    Case report: Pulmonary artery sarcoma diagnosed through rare brain metastases

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    We present the case of a 33-year-old male referred across several hospitals because of suspected chronic thromboembolic pulmonary hypertension (CTEPH). Initially admitted in October 2022 for a recurrent, severe cough and diagnosed with CTEPH, he received anticoagulant therapy. However, his symptoms worsened, necessitating a transfer to another facility for thrombolysis treatment. Following an episode of syncope, an MRI scan revealed a metastatic brain tumor. Subsequently, he experienced a third transfer to our hospital, emergency surgery was performed to alleviate cerebral edema and excise a lesion in the left frontal lobe. Postoperative pathology was inconclusive, but a multidisciplinary team meeting, aided by experienced radiologists, eventually confirmed a diagnosis of pulmonary artery sarcoma (PAS) with systemic metastases. This case underscores the necessity of promptly ruling out PAS in patients presenting with significant emboli in the central pulmonary arteries and suggests early referral to specialized centers for suspected cases

    Comparison of endometrial preparation protocols (natural cycle versus hormone replacement cycle) for frozen embryo transfer (COMPETE) : A study protocol for a randomised controlled trial

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    Funding Information: This study is supported by General Projects of Social Development (2022SF-565). BWM is supported by a NHMRC Investigator grant (GNT1176437). BWM reports consultancy for ObsEva. BMW has received research funding from Ferring and Merck. The other authors have none to declare. Acknowledgements: We thank all the physicians, scientists, and embryologists in our IVF clinic for their assistance with data collection as well the patients for participating in this studyPeer reviewedPublisher PD

    Protective role for collectin‐11 in rheumatoid arthritis in mice

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    OBJECTIVE. Collectin-11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. The goal of this study was to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). METHODS. A murine collagen-induced arthritis (CIA) model, combining both gene deletion of Colec11 and recombinant (rCL-11) treatment approaches were employed. Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines and adaptive immune responses were assessed in CIA mice. Splenic CD11c(+) cells were used to examine the influence of CL-11 on antigen presenting cell (APC) function. Serum levels of CL-11 in RA patients were also examined. RESULTS. Colec11(−/−) mice developed more severe arthritis than WT mice (as determined by disease incidence, clinical arthritis scores and histopathology; P<0.05). Disease severity is associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c(+) cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacological treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum levels of CL-11 was lower in RA patients (n=51) compared to healthy controls (n=53), a serum CL-11 reduction also displays a negative relationship with DAS28, ESR and CRP (P<0.05). CONCLUSION. Our findings demonstrate a novel role for CL-11 in protection against RA, suggesting the underlying mechanism involved suppression of APC activation and subsequent T cell responses

    Association of hepatitis B virus infection status with outcomes of non-small cell lung cancer patients undergoing anti-PD-1/PD-L1 therapy

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    Background: The aim of this study was to evaluate the safety and survival outcomes of anti-programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) monotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) and different hepatitis B virus (HBV) infection status. Methods: Patients with advanced NSCLC and both chronic and/or resolved HBV infection who were treated with anti-PD-(L)1 monotherapy were retrospectively enrolled. The primary endpoint was the safety of PD-1/PD-L1 monotherapy, while the secondary endpoints included the survival outcomes. Results: Of the 62 eligible patients, 10 (16.1%) were hepatitis B surface antigen (HBsAg) positive [chronic hepatitis B (CHB) infection] and 52 (83.9%) were HBsAg negative and HBcAb positive [resolved hepatitis B (RHB) infection]; 42 (67.7%) patients had at least 1 treatment-related adverse event (AE), with 4 patients (6.5%) developing grade 3 AEs and 6 (9.7%) developing hepatic AEs. One CHB patient experienced HBV reactivation during anti-PD-1 immunotherapy due to the interruption of antiviral prophylaxis. The objective response rate and durable clinical benefit (DCB) rate were 17.7% and 29.0%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 23.6 months [95% confidence interval (CI): 14.432.8] and 2.1 months (95% CI: 1.2-3.0), respectively. The DCB rate was significantly higher in the CHB group than in the RHB group (60% vs. 23.1%; P=0.048). Patients with CHB experienced a longer PFS (8.3 vs. 2.0 months; P=0.103) and OS (35.0 vs. 18.2 months, P=0.119) than did RHB patients. Conclusions: Anti-PD-(L)1 monotherapy was safe and effective in patients with NSCLC and HBV infection. This population should not be excluded from receiving immunotherapy in routine clinical practice or within clinical trials if HBV biomarkers are monitored and antiviral prophylaxis is properly used

    PFKFB4 Promotes Breast Cancer Metastasis via Induction of Hyaluronan Production in a p38-Dependent Manner

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    Background/Aims: The bi-functional enzyme 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase-4 (PFKFB4) is highly expressed in many types of cancer and its requirement for tumor survival has been demonstrated in glioma, lung, and prostate cancers. However, whether PFKFB4 plays a role in the tumor metastasis remains uncertain. This study explores the role of PFKFB4 in tumor metastasis and its underlying mechanisms in breast cancer cells. Methods: The expression of PFKFB4 was first analyzed using the Cancer Genome Atlas (TCGA) dataset, and confirmed by immunohistochemical staining of tissue microarray and breast cancer tissues from patient samples. Gain- and loss-of- function approaches were used to investigate the effects of PFKFB4 on breast cancer cell migration in vitro. Orthotopic xenograft model and experimental metastasis model were used to assess the effects of PFKFB4 on breast cancer cell metastasis in vivo. ELISA and immunofluorescence staining were used to examine HA production. Quantitative RT-PCR and western blotting were used to explore the mRNA and protein levels of HAS2, respectively. Results: We found that PFKFB4 enhances the migration/invasiveness of breast cancer cells in vitro as well as in vivo. Notably, the effects of PFKFB4 on migration are mediated by induction of HAS2 expression and HA production. Moreover, PFKFB4-induced HAS2 up-regulation depends upon the activation of p38 signaling. Conclusion: PFKFB4 promotes the metastasis of breast cancer cells via induction of HAS2 expression and HA production in a p38-dependent manner. Therefore, the PFKFB4/p38/HAS2 signaling pathway may serve as a potential therapeutic target for metastatic breast cancer

    A micro surface tension alveolus (MISTA) in a glass microchip

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    We have designed a non-membrane micro surface tension alveolus (MISTA) in a glass microchip for direct gas exchange and micro gradient control. Hemoglobin (Hb) in the liquid phase indicates the rapid gas gradient changes of O-2 and CO2 shifted by the difference in pressure between the liquid and the gas.Anthone Elec. Ltd. (Xiamen, China) ; National Natural Science Foundation of Chin
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