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Background: Evaluation of liver fibrosis played a monumental role in the diagnosis and monitoring of chronic hepatitis B (CHB). We aimed to explore the value of serum N-glycan markers in liver fibrosis. Methods: This multi-center (33 hospitals) study recruited 760 treatment-naïve CHB patients who underwent liver biopsy. Serum N-glycan markers were analyzed by DNA sequencer-assisted fluorophore-assisted with capillary electrophoresis (DSA-FACE) technology. First, we explore the relationship between 12 serum N-glycan markers and the fibrosis stage. Then, we developed a Px score for diagnosing significant fibrosis using the LASSO regression. Next, we compared the diagnostic performances between Px, LSM, APRI, and FIB-4. Finally, we explored the relationships between glycosyltransferase gene and liver fibrosis with RNA-transcriptome sequencing. Results: We included 622 CHB participants: male-dominated (69.6%); median age 42.0 (IQR 34.0–50.0); 287 with normal ALT; 73.0% with significant fibrosis. P5(NA2), P8(NA3), and P10(NA4) were opposite to the degree of fibrosis, while other profiles (except for P0[NGA2]) increased with the degree of fibrosis. Seven profiles (P1[NGA2F], P2[NGA2FB], P3[NG1A2F], P4[NG1A2F], P7[NA2FB], P8[NA3], and P9[NA3Fb]) were selected into Px score. Px score was associated with an increased risk of significant fibrosis (for per Px score increase, the risk of significant fibrosis was increased by 3.54 times (OR = 4.54 [2.63–7.82]) in the fully-adjusted generalized linear model. p for trend was <0.001. The diagnostic performance of the Px score was superior to others. Glycosyltransferase genes were overexpressed in liver fibrosis, and glycosylation and glycosyltransferase-related pathways were significantly enriched. Conclusions: Serum N-glycan markers were positively correlated with liver fibrosis. Px score had good performance in distinguishing significant fibrosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The correlation between the change in foveal thickness measured using optical coherence tomography (OCT) following surgery for infectious endophthalmitis and preoperative and postoperative visual acuity is uncertain, and there are few pertinent studies on this topic. OBJECTIVE: We explored the variations in macular thickness using OCT after emergency vitrectomy for post-cataract infectious endophthalmitis and the relationship between macular thickness with changes in visual function. METHODS: We included 10 cases of post-cataract infectious endophthalmitis. Each patient underwent 25-G vitrectomy. RESULTS: The infection in all 10 patients was under control and visual function improved. Postoperative vitreous humor culture was positive in 8 patients, including 7 cases of coagulase-negative Staphylococcus epidermidis and 1 case of Lactobacillus acidophilus. The average age of these 10 patients was 71.60 ± 8.71 years (P < 0.05, two-tailed). There was no significant correlation between time 2 (the time of onset after cataract surgery) and visual prognosis. The average time 1 (the time of the vitrification surgery caused by the onset of the disease) was 1.45 ± 0.76 days (P < 0.05, two-tailed). The postoperative 3dVA ranged from 0.20 to 3.00, with an average visual acuity of 1.87 ± 1.12, which was superior to the preoperative value (P < 0.01, two-tailed). The correlation between the post3dVA and post 1mVA was significant. The post 1mVA ranged from 0.05 to 2.20, with an average visual acuity of 0.94 ± 0.74 (P < 0.05, two-tailed). The correlation between post 1mVA and post3mVA was significant. Also, paired t -tests comparing preoperative and postoperative visual acuity revealed a significant correlation (P < 0.05, two-tailed). The post3mVA was 0–1.00 with an average visual acuity of 0.44 ± 0.41. The postoperative foveal thickness ranged from 176.00 to 514.00 μ m, with an average thickness of 281.10 ± 113.12 μ m. CONCLUSION: Emergency 25-G minimally invasive vitrectomy can improve visual acuity and decrease the reoperation rate for patients who have acquired post-cataract infectious endophthalmitis. There were significant correlations between age, disease onset to operation time, preoperative and postoperative visual acuity, and postoperative macular thickness. [ABSTRACT FROM AUTHOR]

Background: Hepatic stellate cell hyperactivation is a central link in liver fibrosis development, transforming growth factor β1 (TGF-β1) is a key activator of HSCs. Aims: This study investigated whether anlotinib attenuates CCl4 induced liver fibrosis in mice and explored its antifibrotic mechanism. Methods: We used the human hepatic stellate cell line LX-2 for in vitro assays and used TGF-β1 to induce hepatic fibrosis in LX-2 cells. We analyzed cytotoxicity using a cell-counting kit-8 and transwell chambers to detect the migratory ability of LX-2 cells. Western blotting was used to detect the protein levels of collagen type I, α-smooth muscle actin, and p-Smad3. In addition, mice with CCl4-induced hepatic fibrosis were used as in vivo models. Histopathological examination was performed using H&E staining, Masson's trichrome staining, and immunohistochemistry. Results: Anlotinib significantly reversed TGF-β1-induced protein levels of Col I, α-SMA and p-Smad3 and inhibits migratory and proliferative abilities in vitro using LX-2 cells. CCl4 cause F4 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 12 to 14 (Ishak), a mean ALT measurement of 130 U/L and a mean measurement AST value of 119 U/L in mice. However, the CCl4-induced changes were markedly attenuated by anlotinib treatment, which returned to F2 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 4 to 6 (Ishak), a mean ALT measurement of 40 U/L and a mean measurement AST value of 56 U/L in mice. Conclusions: Our results suggest that anlotinib-mediated suppression of liver fibrosis is related to the inhibition of TGF-β1 signaling pathway. Hepatic stellate cell hyper activation is a central link in liver fibrosis development, transforming growth factor β1 is a key activator of HSCs. Anlotinib is a multi-targeted tyrosine kinase inhibitor that has similar targets to nintedanib, a clinically used anti-pulmonary fibrosis drug. Our study demonstrates an FDA-approved drug—anlotinib—that could prevent liver fibrosis and inflammation. Experiments in cell cultures and mice show that anlotinib can inhibit the activation of hepatic stellate cells by down-regulating the TGFβ1/smad3 pathway, thereby reversing liver fibrosis. In animal experiments, anlotinib showed protective effects on the CCl4-induced liver damage, including ameliorating liver inflammation, reversing liver fibrosis and reducing liver enzymes. This is a very good signal, anlotinib may be useful for halting or reversing the progression of liver fibrosis and could be employed in the development of novel therapeutic drugs for the management of chronic liver diseases. [ABSTRACT FROM AUTHOR]

Two mutations of the I ATP8B1 i gene were identified in the patient and his sister, including 1375C>T mutation in exon 13 and 2025dupT mutation in exon 18 (Figures 3B). In this study, the patient carried two mutations, including the 2025dupT mutation, which is predicted to cause a truncated FIC1 and to completely abrogate the FIC1 protein function. Therefore, we propose that 2025dupT mutation of the I ATP8B1 i gene may largely cause PFIC1 in our patient and could be pathogenic. [Extracted from the article]

Background: Glioma stem‐like cells (GSCs) are greatly responsible for the progression of glioma. Long noncoding RNAs (lncRNAs) play an important role in glioma tumor progression. This study aims to explore the role and underlying mechanism of lncRNA SNHG9 in regulating GSC cell growth. Methods: GSCs were obtained from glioma cells (U87 and U251) and referred to as GSC‐87 and GSC‐251, respectively. The interactions between miR‐326 and SNHG9 or SOX9 were analyzed using luciferase reporter assay. Cell growth of GSCs was evaluated by EdU assay and sphere formation assay. Results: SNHG9 expression was significantly higher in GSC‐87 and GSC‐251 cells than in U87 and U251 cells. SNHG9 overexpression promoted GSC cell growth, whereas SNHG9 knockdown inhibited GSC cell growth. Mechanistically, SNHG9 acted as a competitive endogenous RNA of miR‐326 to elevate the expression of SOX9, a direct target of miR‐326. Moreover, transfection with miR‐326 inhibitor counteracted SNHG9 knockdown‐mediated inhibition of GSC cell growth. Conclusions: SNHG9 facilitates growth of GSCs via the miR‐326/SOX9 axis. This study provides a promising therapeutic target for glioma treatment. [ABSTRACT FROM AUTHOR]

Surface design and engineering is a critical tool to improve the interaction of materials with their surroundings. Immobilization of soft hydrogels is one of the attractive strategies to achieve surface modification. The goal of this review is to provide a comprehensive overview of the different strategies used for surface tethering of hydrogel layers via crosslinking immobilization of pre-fabricated functional polymers. In this strategy, crosslinkable polymers are first prepared via various polymerization techniques or post-functionalization of polymers. Afterwards, the crosslinkable polymers are attached or tethered on the surfaces of substrates using a variety of approaches including photo-crosslinking, click reactions, reversible linkages, etc. For each case, the principles of hydrogel tethering have been explained in detail with representative examples. Moreover, the potential applications of the as-modified substrates in specific cases have also been addressed and overviewed. [ABSTRACT FROM AUTHOR]

Smart materials with controllable responses to various stimulations offer considerable potential in many applications. Herein we report a simple and efficient method to fabricate ionic strength- and thermo-responsive polyethersulfone composite membranes using zwitterionic copolymers of sulfobetaine methacrylamide (SBMI) and sulfobetaine methacrylate (SBMA). The permeability of the modified membranes could be adjusted by varying the ionic strength from 0 mol kg−1 to 1.0 mol kg−1 and/or varying the surrounding temperature from 15 °C to 90 °C, and both the responses were reversible. The thermo-response transition temperature could be regulated by changing the chemical compositions of the zwitterionic copolymers. Furthermore, the zwitterionic copolymer modified membranes exhibited excellent antifouling resistances to protein solutions and surfactant-stabilized oil-in-water emulsions. Their ionic strength- and thermo-responsive flux, separation ability, and excellent antifouling properties endowed the membranes with a wide range of applications in the field of separation. [ABSTRACT FROM AUTHOR]

Hollow fiber membranes with satisfied blood compatibility and antibacterial property are desired in blood purification. Herein, a series of heparin-like copolymers of poly(methyl methacrylate-vinyl pyrrolidone -sodium styrene sulfonate-sodium acrylate) (poly(MMA-VP-SSNa-SA)) were synthesized by free radical solution polymerization. The mixture was directly blended with polyethersulfone (PES) solution to prepare hollow fiber membranes. The membranes were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Blood compatibility of the hollow fiber membranes was evaluated via protein adsorption, platelet adhesion, clotting time, and hemolysis assay. Besides, Ag nanoparticles were immobilized onto the hollow fiber membranes efficiently by a simple and green method, and the antibacterial property and blood compatibility of the Ag-loaded membranes were then investigated. The results indicated that the approach towards blood compatible and antibacterial hollow fiber membrane is efficient and flexible for the modification for membrane materials. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

In this study, random terpolymers of methoxy poly(ethylene glycol)-poly(sodium styrene sulfonate- co-methyl methacrylate) (MPEG-P(SSNa- co-MMA)) integrated with antifouling and anticoagulant properties were synthesized by atom transfer radical polymerization (ATRP) for the first time and confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and gel permeation chromatography (GPC). The terpolymers with desired antifouling and anticoagulant segments were then used as amphiphilic additives to modify polyethersulfone membranes by an engineering blended approach. Water contact angle (WCA) results indicated that the surface hydrophilicity of the modified membranes enhanced. Protein ultrafiltration experiments showed that the antifouling ability of the modified membranes increased. In addition, the modified membranes showed decreased protein adsorption (bovine serum albumin, BSA), suppressed platelet adhesion, and prolonged activated partial thromboplastin time (APTT). Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The traditional TCP performs worse in high-bandwidth and wireless network. This paper proposed an end-to-end virtual router model and a PI rate control algorithm at sender. According to the change of RTTs, the algorithm calculated the data sending rate using PI controller, stabilized the queue length of bottleneck router at a target level, reduced congestion packet loss and the mistaken adjustment to congestion window caused by wireless link error packet loss. The simulation results show that, the new mechanism can flexibly control the queue length, improve the stability and throughput of the network. [ABSTRACT FROM AUTHOR]

The current study aims to endow polyethersulfone (PES) hollow fiber membranes (HFMs) with improved pH-sensitivity by blending a random copolymer of poly(methyl methacrylate-co-maleic anhydride) (P(MMA-MA)). It was found that PES membrane modified by random copolymer had more obvious pH-sensitivity than those by alternative copolymer; while low molecular weight copolymer modified PES membrane had no pH-sensitivity. P(MMA-MA) was synthesized by a controlled dosing method via free radical polymerization and characterized by Fourier transform infrared spectroscopy (FTIR) analysis, nuclear magnetic resonance (1H NMR), elemental analysis, gel permeation chromatography technique (GPC), and differential scanning calorimetry (DSC) measurement. Scanning electron microscopy (SEM) was used to investigate the morphology of the HFMs. The modified HFMs showed excellent pH-sensitivity, pH-reversibility and hysteresis of water flux. Through the ultrafiltration of PEG solution, we investigated the pore size change and the electroviscous effect on the water flux of the modified HFMs. Meanwhile, the modified membranes were stable with respect to the mechanical force (pressure) and exhibited good ability of Cu2+adsorption. [ABSTRACT FROM AUTHOR]

B-lymphoma mouse Moloney leukemia virus insertion region 1 ( Bmi1), a member of the polycomb group, has elevated expression and is involved in the pathogenesis of various aggressive cancers, including nasopharyngeal carcinoma ( NPC). To date, the mechanisms underlying the high expression of Bmi1 in NPC remain obscure. To gain new insights into the transcriptional regulation of BMI1, we cloned and characterized the promoter region of BMI1. Luciferase reporter assays demonstrated that the region from −783 to +375 showed significant promoter activity. With the use of a series of 5′-deletion and 3′-deletion promoter constructs in luciferase reporter assays, the +167/+232 and −536/−134 regions were found to be sufficient for full promoter activity. Transcriptional activity of the BMI1 promoter was dependent on the Sp1 binding site cluster (+181/+214) as well as the E-box elements (−181), and was abolished after mutation of the two cis-elements. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated that Sp1 bound to the region from +181 to +214 within the BMI1 promoter. In addition, gain-of-function and loss-of-function analyses revealed that Sp1 augmented Bmi1 expression. Further investigations using immunohistochemistry and quantitative RT-PCR disclosed a significant positive correlation between the expression of Sp1 and Bmi1 in normal nasopharyngeal epithelial cells, NPC cells, and NPC tissue specimens. In addition, Myc, the known transcription factor for BMI1 in neuroblastomas, also activated the transcription of BMI1 through binding to the E-box element (−181) within its promoter, and showed a positive correlation with the m RNA level of BMI1 in NPC. In conclusion, these findings provide valuable mechanistic insights into the role of Sp1 and c- Myc in BMI1 transcription in NPC, and suggest that targeting of Sp1 or c-Myc may be a potential therapeutic strategy for NPC. [ABSTRACT FROM AUTHOR]

The overexpression of centromere protein H (CENPH), one of the fundamental components of the human active kinetochore, has been shown to be closely associated with human cancers. However, the mechanism of its transcriptional regulation has not been reported. The aim of the present study was to investigate the regulatory elements for the transcriptional regulation of CENPH in nasopharyngeal carcinoma cells. To characterize the CENPH promoter and identify regulatory elements, we cloned 1015 bp (−975/+40 bp) of the 5′-flanking region of the CENPH gene from immortalized normal nasopharyngeal epithelial cells (Bmi-1/NPEC). Functional analysis established a minimal region (−140/−87 bp) involved in the regulation of human CENPH promoter activity. Through site-directed mutagenesis, a transactivation assay, chromatin immunoprecipitation, and electrophoretic mobility shift assay, we found that the Sp1/Sp3 transcription factors could bind to the CENPH promoter in vitro and in vivo, and that they regulated CENPH promoter activation in human nasopharyngeal carcinoma cells. Furthermore, Sp1 and Sp3 were highly expressed in nasopharyngeal carcinoma cells. Knockdown of Sp1 and Sp3 by small interfering RNA or inhibition of Sp1 and Sp3 activity by mithramycin A decreased CENPH mRNA expression, whereas the exogenous expression of Sp1 and Sp3 upregulated CENPH mRNA expression. Taken together, our results indicate that Sp1 and Sp3 bind to the CENPH minimal promoter and function as a regulator of the transcription of CENPH in human nasopharyngeal carcinomas. [ABSTRACT FROM AUTHOR]