73 research outputs found

    The off-target effects of AID in carcinogenesis

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    Activation-induced cytidine deaminase (AID) plays a crucial role in promoting B cell diversification through somatic hypermutation (SHM) and class switch recombination (CSR). While AID is primarily associated with the physiological function of humoral immune response, it has also been linked to the initiation and progression of lymphomas. Abnormalities in AID have been shown to disrupt gene networks and signaling pathways in both B-cell and T-cell lineage lymphoblastic leukemia, although the full extent of its role in carcinogenesis remains unclear. This review proposes an alternative role for AID and explores its off-target effects in regulating tumorigenesis. In this review, we first provide an overview of the physiological function of AID and its regulation. AID plays a crucial role in promoting B cell diversification through SHM and CSR. We then discuss the off-target effects of AID, which includes inducing mutations of non-Igs, epigenetic modification, and the alternative role as a cofactor. We also explore the networks that keep AID in line. Furthermore, we summarize the off-target effects of AID in autoimmune diseases and hematological neoplasms. Finally, we assess the off-target effects of AID in solid tumors. The primary focus of this review is to understand how and when AID targets specific gene loci and how this affects carcinogenesis. Overall, this review aims to provide a comprehensive understanding of the physiological and off-target effects of AID, which will contribute to the development of novel therapeutic strategies for autoimmune diseases, hematological neoplasms, and solid tumors

    Association between Portal Vein Thrombosis and Survival in Non-Liver-Transplant Patients with Liver Cirrhosis: A Systematic Review of the Literature

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    A systematic review of the literature was performed to analyze the association between portal vein thrombosis (PVT) and survival in non-liver-transplant patients with liver cirrhosis. PubMed, EMBASE, and Cochrane Library databases were searched for all relevant papers which evaluated the prognostic value of PVT in predicting the survival of liver cirrhosis. Meta-analyses were not conducted because the ways of data expression and lengths of follow-up were heterogeneous among studies. Overall, 13 papers were included. The 5-day, 6-week, and 1-year mortality were investigated in 1, 3, and 1 studies, respectively; and all of them were not significantly different between cirrhotic patient with and without PVT. By comparison, the 3-year mortality was reported in 1 study; and it was significantly increased by the presence of PVT. The overall mortality was analyzed in 5 studies; and the association with overall mortality and PVT was significant in 4 studies, but not in another one. However, as for the cirrhotic patients undergoing surgical or interventional shunts, the overall mortality was not significantly associated with the presence of PVT in 4 studies. In conclusion, the presence of PVT might be associated with the long-term mortality in non-liver-transplant patients with liver cirrhosis, but not with the short-term mortality

    Cyclization reaction of amines with dialkyl carbonates to yield 1,3-oxazinan-2-ones

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    A number of six-membered cyclic carbamates (oxazinanones) were synthesized from the reaction of a primary amine or hydrazine with a dicarbonate derivative of 1,3-diols in a one-pot reaction, in good yield, short time span, and in the absence of a solvent. The reaction proceeds in two steps: an intermolecular reaction to give a linear intermediate and an intramolecular cyclization to yield the cyclic carbamate. This is the first example of a carbonate reacting selectively and sequentially, firstly at the carbonyl center to form a linear carbamate and then as a leaving group to yield a cyclic carbamate

    Cytomegalovirus Infection May Trigger Adult-Onset Still's Disease Onset or Relapses

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    Previous studies have revealed that several micro-organisms, especially DNA viruses, have been associated with adult-onset Still's disease (AOSD). However, there are no studies on the relationship between the presence of viral infections in AOSD patients with disease occurrence and reactivation. In the present study, we aimed to investigate the presence of antibodies against virus, virus DNA load and nucleic acid sensors in AOSD patients. Anti-viral antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples from 100 AOSD patients and 70 healthy controls (HCs). The copy number of cytomegalovirus (CMV) DNA in 100 AOSD patients was detected by PCR. The expression levels of nucleic acid sensors interferon gamma-inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) in peripheral blood mononuclear cell (PBMC) and skin from AOSD patients and HCs were analyzed by PCR and immunohistochemistry. The levels of antibodies against CMV were significantly higher in AOSD patients compared to HCs. Moreover, the level of anti-CMV IgM antibody was significantly increased in patients with fever, sore throat, arthralgia and rash. CMV DNA was found in plasma of AOSD patients with disease new-onset and relapse. Furthermore, the copy number of CMV DNA significantly increased in patients with fever, sore throat, arthralgia and rash. And the significant associations of the CMV DNA level with the levels of leukocytes, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were observed. Moreover, we found an upregulation of cytoplasmic DNA-sensing receptor IFI16 and AIM2 in PBMC and skin from AOSD patients. In conclusion, our results showed that CMV infection may play a role in the initiation or amplification of inflammatory responses in AOSD

    A simplified method for determination of Philip-Dunne infiltration parameters

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    The Philip-Dunne falling-head infiltration for determining the parameters of soil water movement is a relatively simple procedure, yet the calculation is still complicated. This study develops a simplified method for determining soil saturated hydraulic conductivity ks and Green-Ampt wetting front suction ψ. Field Philip-Dunne infiltration tests are performed in a loam soil under different initial head heights (30, 40, and 50 cm) at 45 test points. The relationship between infiltration time ti and the parameters ks and ψ is explored. The results show that Δθ within the range of 0.015–0.147 has little influence on ks or ψ in the test soil, and prediction of the two parameters using mean Δθ meets the accuracy requirements. ks is significantly negatively correlated with ti and best predicted by 1/tmed; the prediction accuracy of the linear function is strongly influenced by the initial head height h0. There is a significant relationship between ψ and tmax/tmed, and h0 has little influence on the prediction accuracy of the power function. Therefore, the simplified models based on 1/tmed and tmax/tmed can be used for field-scale determination of the parameters ks and ψ in loam soil, with an overall error below 10%

    Seismic Behavior Analysis of Recycled Aggregate Concrete-Filled Square Steel Tube Frames

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    In this study, the seismic behavior of a recycled aggregate concrete-filled square steel tube (S-RACFST) frame under different design conditions was investigated. Based on previous studies, a finite element model for the seismic behavior of the S-RACFST frame was developed. Moreover, the axial compression ratio, beam–column line stiffness ratio, and yield bending moment ratio of the beam–column were regarded as the variation parameters. It was through these parameters that the seismic behavior of eight S-RACFST frame finite element specimens was discussed. The seismic behavior indexes, such as the hysteretic curve, ductility coefficient, energy dissipation coefficient, and stiffness degradation were obtained—which, in turn, revealed the influence law and the degree of the design parameters regarding seismic behavior. Moreover, the sensitivity of the various parameters with respect to the seismic behavior of the S-RACFST frame was evaluated via grey correlation analysis. The results show that the hysteretic curves of the specimens were fusiform and full with respect to the different parameters. Firstly, with the axial compression ratio increasing from 0.2 to 0.4, the ductility coefficient increased by 28.5%. In addition, the equivalent viscous damping coefficient of the specimen with the axial compression ratio of 0.4 was 17.9% higher than that of the specimen with the axial compression ratio of 0.2, which was 11.5% as well as that with an axial compression ratio of 0.3. Second, when the line stiffness ratio rises from 0.31 to 0.41, the specimens’ bearing capacity and displacement ductility coefficient both get better. However, the displacement ductility coefficient gradually decreases when the line stiffness ratio is greater than 0.41. As a result, an optimal line stiffness ratio (0.41) thus exhibits good energy dissipation capacity. Thirdly, with the increase in the yield bending moment ratio from 0.10 to 0.31, the bearing capacity of the specimens improves. In addition, the positive and negative peak loads increased by 16.4% and 22.8%, respectively. Moreover, the ductility coefficients were all close to three, thus demonstrating good seismic behavior. The stiffness curve of the specimen with a large yield bending moment ratio with respect to the beam–column, is higher than those that possess a small beam–column yield moment ratio. In addition, the yield bending moment ratio of the beam–column possesses a significant influence on the seismic behavior of the S-RACFST frame. Furthermore, the yield bending moment ratio of the beam–column should be considered first in order to ensure the seismic behavior of the S-RACFST frame

    Perforation of Palate in Granulomatosis With Polyangiitis

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    Response of Water-Salt Migration to Brackish Water Irrigation with Different Irrigation Intervals and Sequences

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    Establishing methods for scientific and rational use of brackish water resources is the key to farmland irrigation in the Yellow River Delta region of China. In this study, we conducted laboratory simulation experiments with soil columns and monitored the changes in water infiltration and salt distribution under eight irrigation treatments, including four intervals (0, 30, 60, and 90 min between irrigations) and two sequences (brackish-brackish-fresh water and brackish-fresh-brackish water). The results showed that the duration of water infiltration into the soil was higher under intermittent irrigation than continuous irrigation, with the highest value recorded at the 90-min irrigation interval. There was no significant difference in the mean soil water content between the brackish-brackish-fresh water (28.01–29.71%) and brackish-fresh-brackish water (28.85–29.98%) irrigation treatments. However, the mean soil desalination rate of the brackish-brackish-fresh irrigation treatment (42.51–46.83%) was higher than that of the brackish-fresh-brackish irrigation treatment (39.48–46.47%), and a much higher soil desalination rate was observed at the 90-min irrigation interval, compared with the other intervals. In conclusion, brackish-brackish-fresh water irrigation at longer time intervals (e.g., 90 min between irrigations) is conducive to reduce soil salt content in the surface soil in the study region

    Overview on Fault Tolerance Strategies of Composite Service in Service Computing

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    In order to build highly reliable composite service via Service Oriented Architecture (SOA) in the Mobile Fog Computing environment, various fault tolerance strategies have been widely studied and got notable achievements. In this paper, we provide a comprehensive overview of key fault tolerance strategies. Firstly, fault tolerance strategies are categorized into static and dynamic fault tolerance according to the phase of their adoption. Secondly, we review various static fault tolerance strategies. Then, dynamic fault tolerance implementation mechanisms are analyzed. Finally, main challenges confronted by fault tolerance for composite service are reviewed
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