Publications by authors named "Ze Hu"

36 Publications

Changes of microbial community structure during the initial stage of biological clogging in horizontal subsurface flow constructed wetlands.

Bioresour Technol 2021 Oct 12;337:125405. Epub 2021 Jun 12.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

The clogging is a universal problem in constructed wetlands, where microorganisms play an essential role. However, the implication of micro-organism variation due to the clogging is not clear. Four horizontal subsurface flow constructed wetlands (HFCWs) were designed and operated to simulate the process of clogging. The wetland treatment performance and microbial community variation were investigated by regularly monitoring. Results showed the substrate filtration rate and the total phosphorous (TP) removal efficiency consistently decreased and the chemical oxygen demand (COD) and total nitrogen (TN) removal efficiency were at the range of 50%-85% and 10-20%, respectively. The sequencing results indicated that the clogging could affect the richness of bacterial community. The bacterial variation could be attributed to the dissolved oxygen decreasing and organic matter accumulation in the initial clogging period. These findings are expected to provide some theoretical reference for developing the biological methods to indicate the initial clogging in constructed wetlands.
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http://dx.doi.org/10.1016/j.biortech.2021.125405DOI Listing
October 2021

A clinical scoring system for predicting tumor recurrence after percutaneous radiofrequency ablation for 3 cm or less hepatocellular carcinoma.

Sci Rep 2021 Apr 15;11(1):8275. Epub 2021 Apr 15.

Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan City, 528400, Guangdong Province, China.

Preoperative prediction of tumor recurrence after radiofrequency ablation (RFA) in patients with early hepatocellular carcinoma (HCC) is helpful for clinical decision-making before treatment. A total of 162 patients with HCC of 3 cm or less who were completely ablated by percutaneous RFA were divided into a derivation cohort (n = 108) and a validation cohort (n = 54). Based on X-Tiles software, Kaplan-Meier curve analysis and COX multivariate analysis to obtain valuable predictive indicators, a clinical scoring system for predicting tumor recurrence was established. In the verall cohort, derivation cohort and validation cohort, we found circulating tumor cells (CTC) > 2/3.2 mL, alpha-fetoprotein (AFP) > 20 ng/mL, and des-γ-carboxyprothrombin (DCP) > 40 mAU/mL, maximum tumor diameter > 20 mm, and the number of multiple tumors (≥ 2) are independent risk factors affecting tumor recurrence. Each independent risk factor was assigned a score of 1 to construct a predictive clinical scoring system, and X-Tiles software was used to divide the clinical score into a low-risk group (0 score-1 score), a medium-risk group (2 scores-3 scores), and a high-risk group (4 scores-5 scores). The cumulative tumor recurrence rates of patients in the low-risk group, middle-risk group, and high-risk group in 1 year, 2 years, and 3 years were 19.4%/27.5%/30.9%, 37.0%/63.2%/79.9% and 68.2%/100%/100%, respectively (Low-risk group vs medium-risk group: P < 0.001; medium-risk group vs high-risk group: P < 0.001). This clinical scoring system can predict the prognosis of patients with HCC of 3 cm or smaller undergoing percutaneous RFA, which has certain application value for making preoperative clinical decisions.
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http://dx.doi.org/10.1038/s41598-021-87782-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050297PMC
April 2021

Evidence of the Berezinskii-Kosterlitz-Thouless phase in a frustrated magnet.

Nat Commun 2020 Nov 6;11(1):5631. Epub 2020 Nov 6.

Department of Physics and Beijing Key Laboratory of Opto-electronic Functional Materials and Micro-nano Devices, Renmin University of China, Beijing, 100872, China.

The Berezinskii-Kosterlitz-Thouless (BKT) mechanism, building upon proliferation of topological defects in 2D systems, is the first example of phase transition beyond the Landau-Ginzburg paradigm of symmetry breaking. Such a topological phase transition has long been sought yet undiscovered directly in magnetic materials. Here, we pin down two transitions that bound a BKT phase in an ideal 2D frustrated magnet TmMgGaO, via nuclear magnetic resonance under in-plane magnetic fields, which do not disturb the low-energy electronic states and allow BKT fluctuations to be detected sensitively. Moreover, by applying out-of-plane fields, we find a critical scaling behavior of the magnetic susceptibility expected for the BKT transition. The experimental findings can be explained by quantum Monte Carlo simulations applied on an accurate triangular-lattice Ising model of the compound which hosts a BKT phase. These results provide a concrete example for the BKT phase and offer an ideal platform for future investigations on the BKT physics in magnetic materials.
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http://dx.doi.org/10.1038/s41467-020-19380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648753PMC
November 2020

Platinum-based nanocomposite as oxygen reduction catalyst for efficient signal amplification: Toward building of high-performance photocathodic immunoassay.

Biosens Bioelectron 2020 Nov 28;168:112563. Epub 2020 Aug 28.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, Shandong Key Laboratory of Biochemical Analysis, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China. Electronic address:

Photocathodic bioassays have shown great potential to apply in real bio-sample detection owning to their intrinsic abilities against interference from reductive species. However, the pursuit of photocathodic bioassays with excellent detection performance is still in the infancy. Herein, an advanced signal amplifier of platinum-based nanocatalyst with efficient oxygen reduction capability was explored to build a high-performance photocathodic immunoassay. The target model of carbohydrate antigen 19-9 (CA19-9, Ag) was used for describing the sensing platform. Specifically, the nontoxic Au/CuBiO photocathode was first prepared by decorating Au nanoparticles on CuBiO nanofilm and was used as the matrix to anchor capture CA19-9 antibody (Ab). Platinum (Pt) nanoparticles were loaded on graphene (GR) nanosheet to form Pt/GR nanocomposite, which was utilized as signal amplifier conjugating with signal CA19-9 antibody (Ab). When specific sandwich immunoreaction happened, the Pt/GR played the role of an efficient nanocatalyst to accelerate the reduction reaction of electron acceptor of oxygen in the electrolyte, causing evidently enhanced cathodic photocurrent signal. By incorporating this superior signal amplification strategy into the anti-interference photocathodic immunoassay, highly sensitive and specific detection of target Ag was realized. This work pioneers a new perspective for the design of advanced photocathodic bioanalysis for various targets of interest.
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http://dx.doi.org/10.1016/j.bios.2020.112563DOI Listing
November 2020

Preoperative evaluation and prediction of clinical scores for hepatocellular carcinoma microvascular invasion: a single-center retrospective analysis.

Ann Hepatol 2020 Nov - Dec;19(6):654-661. Epub 2020 Aug 5.

Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-sen University, Zhongshan City, Guangdong Province, China. Electronic address:

Introduction: Microvascular invasion (MVI) of is generally considered to be an important prognostic factor for hepatocellular carcinoma (HCC) after operation, An accurate prediction of MVI before operation is helpful for clinical decision-making before operation.

Material And Methods: A retrospective analysis of 227 cases of hepatocellular carcinoma patients after hepatectomy has been confirmed the pathological result whether there was MVI, and has been determined the independent risk factors of MVI. Based on these independent risk factors, we constructed a clinical scoring risk model for predicting MVI.

Results: Among the 227 patients with HCC, 74 (34.6%) were MVI positive. Using receiver operating characteristic (ROC) curve and logistic regression model, we found that alpha-fetoprotein(AFP)≥158 ng/mL(odds ratio[OR] = 4.152,95% confidence interval [95%CI]:1.602∼10.760,p = 0.003), Des-γ-carboxy prothrombin (DCP)≥178mAU/mL(OR = 9.730,95%CI:3.392∼27.910,p < 0.001), circulating tumor cells (CTCs)≥3/3.2 ml(OR = 7.747,95%CI:3.019∼19.881,P < 0.001), maximum tumor diameter≥59 mm(OR = 3.467,95%CI:1.368∼8.669,p = 0.008) and tumor margin unsmoothness(OR = 0.235,95%CI:0.096∼0.573,p = 0.001) were independent risk factors for MVI, they predicted that the area under the curve of MVI was 0.752, 0.777, 0.857, 0.743 and 0.333, respectively. Based on these five independent risk factors, we constructed a clinical scoring risk model for predicting MVI. The model predicts that the area under the curve of MVI is 0.922, and its prevalence rate from 0 to 5 are 3.1%(1/32), 5.3%(4/76), 12.2%(5/41), 66.7%(20/30), 87.9%(29/33), 100%(15/15), respectively (P < 0.001).

Conclusion: Based on AFP, DCP, CTC, maximum tumor diameter and tumor margin unsmoothness, we constructed a model to predict the risk of MVI clinical score, so as to make a more accurate individualized treatment plan before operation, which has important clinical significance and application prospect to improve the curative effect of HCC.
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http://dx.doi.org/10.1016/j.aohep.2020.07.002DOI Listing
August 2020

Study on a New Electromagnetic Flow Measurement Technology Based on Differential Correlation Detection.

Sensors (Basel) 2020 Apr 28;20(9). Epub 2020 Apr 28.

College of Mechanical and Electronic Engineering, Southwest Petroleum University, Chengdu 610500, China.

Under the conditions of low flow rate and strong noise, the current electromagnetic flowmeter (EMF) cannot satisfy the requirement for measurement or separate the actual flow signal and interference signal accurately. Correlation detection technology can reduce the bandwidth and suppress noise effectively using the periodic transmission of signal and noise randomness. As for the problem that the current anti-interference technology cannot suppress noise effectively, the noise and interference of the electromagnetic flowmeter were analyzed in this paper, and a design of the electromagnetic flowmeter based on differential correlation detection was proposed. Then, in order to verify the feasibility of the electromagnetic flow measurement system based on differential correlation, an experimental platform for the comparison between standard flow and measured flow was established and a verification experiment was carried out under special conditions and with flow calibration measurements. Finally, the data obtained in the experiment were analyzed. The research result showed that an electromagnetic flowmeter based on differential correlation detection satisfies the need for measurement completely. The lower limit of the flow rate of the electromagnetic flowmeter based on the differential correlation principle could reach 0.084 m/s. Under strong external interferences, the electromagnetic flowmeter based on differential correlation had a fluctuation range in output value of only 10 mV. This shows that the electromagnetic flowmeter based on the differential correlation principle has unique advantages in measurements taken under the conditions of strong noise, slurry flow, and low flow rate.
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http://dx.doi.org/10.3390/s20092489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248810PMC
April 2020

Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis.

Theranostics 2020 3;10(6):2803-2816. Epub 2020 Feb 3.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

: Our previous study demonstrated that the disruption of cholesterol homeostasis promotes tubulointerstitial injury in diabetic nephropathy (DN). This study aimed to further investigate the effects of gut microbiota dysbiosis on this process and explored its potential mechanism. : Diabetic rats treated with broad-spectrum oral antibiotics or faecal microbiota transplantation (FMT) from the healthy donor group and human kidney 2 (HK-2) cells stimulated with sodium acetate were used to observe the effects of gut microbiota on cholesterol homeostasis. The gut microbiota distribution was measured by 16S rDNA sequencing with faeces. Serum acetate level was examined by gas chromatographic analysis. Protein expression of G protein coupled receptor 43 (GPR43) and molecules involved in cholesterol homeostasis were assessed by immunohistochemical staining, immunofluorescence staining, and Western Blotting. : Depletion of gut microbiota significantly attenuated albuminuria and tubulointerstitial injury. Interestingly, serum acetate levels were also markedly decreased in antibiotics-treated diabetic rats and positively correlated with the cholesterol contents in kidneys. An study demonstrated that acetate significantly increased cholesterol accumulation in HK-2 cells, which was caused by increased expression of proteins mainly modulating cholesterol synthesis and uptake. As expected, FMT effectively decreased serum acetate levels and alleviated tubulointerstitial injury in diabetic rats through overriding the disruption of cholesterol homeostasis. Furthermore, GPR43 siRNA treatment blocked acetate-mediated cholesterol homeostasis dysregulation in HK-2 cells through decreasing the expression of proteins governed cholesterol synthesis and uptake. : Our studies for the first time demonstrated that the acetate produced from gut microbiota mediated the dysregulation of cholesterol homeostasis through the activation of GPR43, thereby contributing to the tubulointerstitial injury of DN, suggesting that gut microbiota reprogramming might be a new strategy for DN prevention and therapy.
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http://dx.doi.org/10.7150/thno.40571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052905PMC
May 2021

Current Applications of Gas Sensor Based on 2-D Nanomaterial: A Mini Review.

Front Chem 2019 10;7:839. Epub 2019 Dec 10.

Electrical and Mechanical Engineering Department, Southwest Petroleum University, Chengdu, China.

Gas sensor, as one of the most important devices to detect noxious gases, provides a vital way to monitor the concentration and environmental information of gas in order to guarantee the safety of production. Therefore, researches on high sensitivity, high selectivity, and high stability have become hot issues. Since the discovery of the nanomaterial, it has been increasingly applied to the gas sensor for its distinguishing surface performances. However, 0-D and 1-D nanomaterials, with limited electronic confinement effect and surface effect, cannot reach the requirement for the production of gas sensors. This paper gives an introduction about the current researching progress and development trend of 2-D nanomaterials, analyzes the common forms of 2-D nanoscale structure, and summarizes the mechanism of gas sensing. Then, widely concerned factors including morphological properties and crystalline structure of 2-D nanomaterial, impact of doped metal on the sensibility of gas sensors, impact of symmetry, and working temperature on the selectivity of gas sensors have been demonstrated in detail. In all, the detailed analysis above has pointed out a way for the development of new 2-D nanomaterial and enhancing the sensibility of gas sensors.
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http://dx.doi.org/10.3389/fchem.2019.00839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914763PMC
December 2019

Eu-Activated Green-Emitting Phosphor Obtained from Eu Ions doping Zeolite-3A in Air Surroundings and Its Efficient Green Light-Emitting Diodes.

Nanoscale Res Lett 2019 Aug 28;14(1):298. Epub 2019 Aug 28.

Key Laboratory of Materials Physics and Anhui Key Laboratory of Nanomaterials and Nanotechnology, Institute of Solid State Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, P.O. Box 1129, Hefei, 230031, People's Republic of China.

Eu-activated phosphors are widely applied in lighting and display areas because of their good optical performance. In this paper, an excellent green-emitting zeolite-3A: 1.3 wt% Eu phosphor is prepared by a green and eco-friendly high-thermal reaction method without any reducing atmosphere or agents. Meanwhile, the reducing mechanism from Eu ions to Eu ions is investigated. The experiment results show that the morphology, crystal structure, and luminescent property are affected by sintering temperature. The resulting sample shows the broad excitation band is in the range of 310-450 nm and the peak of the broad emission band is located at 523 nm. Furthermore, zeolite-3A: 1.3 wt% Eu phosphor is encapsulated on a commercial UV-emitting chip to fabricate a purity green light-emitting diode (LED) with the Commission Internationale de L'Eclairage (CIE) color coordinates at (0.295, 0.537).
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http://dx.doi.org/10.1186/s11671-019-3130-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713767PMC
August 2019

Urinary podocyte microparticles are associated with disease activity and renal injury in systemic lupus erythematosus.

BMC Nephrol 2019 08 5;20(1):303. Epub 2019 Aug 5.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, NO. 87, Ding Jia Qiao Road, Nang Jing City, 210009, Jiang Su Province, China.

Background: New non-invasive biomarkers are demanded to identify renal damage in various autoimmune-associated kidney diseases. Glomerular podocyte damage mediated by systemic lupus erythematosus (SLE) plays an important role in the pathogenesis and progression of lupus nephritis (LN). This study evaluated whether the podocyte-derived microparticles (MPs) were novel biomarkers of clinical and histological features in SLE patients with LN.

Methods: A cross-sectional study, including 34 SLE patients and 16 healthy controls, was designed. Urinary annexin V podocalyxin MPs of all participants were quantified by flow cytometry. The correlation of podocyte-derived MPs with clinical and histological parameters of SLE patients was analysed.

Results: The number of annexin V podocalyxin MPs from urine samples were markly increased in patients with SLE. Furthermore, the level of urinary podocyte-derived MPs was positively correlated with the SLE Disease Activity Index (SLEDAI) score, anti-dsDNA antibody titre, erythrocyte sedimentation rate, and proteinuria. Conversely, it was negatively correlated with the level of complement C3 and serum albumin. The number of urinary podocyte-derived MPs was significantly increased in SLE patients with high activity indices. Receiver operating characteristic (ROC) curves were calculated to assess the power for podocyte-derived MP levels in differentiating between SLE patients with and without LN. Podocyte-derived MP levels were able to differentiate between SLE patients with mild disease activity, as well as those with moderate and above disease activity. SLE patients showed increased podocyte-derived MP excretion into the urine.

Conclusions: These findings suggest that the change in urinary podocyte-derived MP levels could be useful for evaluating and monitoring SLE disease activity.
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http://dx.doi.org/10.1186/s12882-019-1482-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683479PMC
August 2019

[Therapeutic effects of Bianyanning decoction on acute pharyngitis in rats and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2019 Jan;35(1):19-22

Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Disease, Enshi 445000.

Objective: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application.

Methods: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia.

Results: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly.

Conclusion: Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.
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http://dx.doi.org/10.12047/j.cjap.5720.2019.005DOI Listing
January 2019

External right-angle measurement using a two-autocollimator system.

Appl Opt 2019 Feb;58(4):1158-1163

We report on a non-contact method for external right-angle measurement using two autocollimators. A precise mathematical model is deduced to evaluate and deduct the measuring error. The values measured with our method are very coincident compared with the results measured by a ZYGO interferometer. The measuring accuracy is superior to 0.1 arcsec for the right-angle errors within 3.0 arcsec and becomes 0.4 arcsec for the extended right-angle errors within 8.0 arcsec. This method can be widely used in situations for external right-angle measurement, such as angle measurement for the body of torsion balance and test mass in spaceborne laser interferometry.
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http://dx.doi.org/10.1364/AO.58.001158DOI Listing
February 2019

Caspase 3/ROCK1 pathway mediates high glucose-induced platelet microparticles shedding.

Biochem Biophys Res Commun 2019 02 31;509(2):596-602. Epub 2018 Dec 31.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Background: Platelet microparticles (PMPs) are closely associated with diabetic macrovascular complications. This study aimed to explore the underlying mechanisms of high glucose-induced PMPs generation.

Methods: Washed platelets, obtained from the plasma of healthy male Sprague-Dawley rats, were incubated with high glucose. PMPs were isolated using gradient centrifugation and counted by flow cytometry. Expression and activity of ROCK1 and caspase3 were evaluated by real-time PCR, Western blotting, and activity assay kit.

Results: High glucose enhanced PMPs shedding in the presence of collagen. The mRNA and protein levels of ROCK1, but not ROCK2, were increased in platelets incubated with high glucose. Y-27632, an inhibitor of ROCK, blocked the increased PMPs shedding induced by high glucose. Expression and activity of caspase3 were elevated in platelets under the high glucose conditions. Z-DVED-FMK, a caspase3 inhibitor, inhibited ROCK1 activity and decreased the PMPs generation under high glucose.

Conclusion: High glucose increased PMPs shedding via caspase3-ROCK1 signal pathway.
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http://dx.doi.org/10.1016/j.bbrc.2018.12.166DOI Listing
February 2019

Aspirin attenuates podocyte injury in diabetic rats through overriding cyclooxygenase-2-mediated dysregulation of LDL receptor pathway.

Int Urol Nephrol 2019 Mar 2;51(3):551-558. Epub 2019 Jan 2.

Institute of Nephrology, Zhong Da Hospital, Medical School of Southeast University, NO. 87, Ding Jia Qiao Road, Nang Jing, 210009, Jiang Su, China.

Aim: This study aimed to investigate the effects of aspirin on podocyte injury and its underlying mechanisms in diabetic nephropathy (DN).

Methods: Eight-week-old male Sprague-Dawley rats were divided into three groups: non-diabetic rats (Control), streptozotocin-induced diabetic rats (DM), and diabetic rats treated with aspirin (DM + Aspirin) for 12 weeks. Intracellular lipid accumulation was evaluated by Oil Red O staining and quantitative free cholesterol assays. Podocyte injury and the levels of COX-2, inflammatory cytokines, and low-density lipoprotein receptor (LDLr) pathway-related proteins were evaluated by electron microscopy, immunohistochemical staining, and Western blotting, respectively.

Results: Lipid levels and urinary albumin-creatinine ratios were higher in the DM rats than in the Control rats. Periodic acid-Schiff staining showed glomerular hypertrophy and mild mesangial area widening in the DM rats. Electron microscopy showed that the podocyte foot processes were significantly flattened or absent in the DM rats. The protein expression levels of WT-1 and nephrin in the podocytes of DM rats were reduced. Interestingly, lipid accumulation in the kidneys of DM rats was significantly increased due to increased protein expression levels of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), SREBP-2, cyclooxygenase-2 (COX-2), and inflammatory cytokines. Confocal immunofluorescent staining showed that COX-2 and WT-1 were co-expressed. Furthermore, COX-2 protein expression levels were positively correlated with LDLr protein expression levels. However, when COX-2 expression was inhibited by aspirin, these changes in the DM rats were significantly attenuated.

Conclusion: Aspirin attenuates podocyte injury in DN, which may be through COX-2-mediated dysregulation of LDLr pathway.
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http://dx.doi.org/10.1007/s11255-018-2059-7DOI Listing
March 2019

The Release of Monocyte-Derived Tissue Factor-Positive Microparticles Contributes to a Hypercoagulable State in Idiopathic Membranous Nephropathy.

J Atheroscler Thromb 2019 Jun 15;26(6):538-546. Epub 2018 Nov 15.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University.

Aim: Idiopathic membranous nephropathy (IMN) is an immune-mediated inflammatory disease characterized by a high risk of thromboembolic complications. Microparticles (MPs), a type of extracellular vesicles, have procoagulant properties, especially when they display tissue factor (TF). This study aimed to investigate whether circulating TF-positive MPs contributed to the hypercoagulable state in patients with IMN.

Methods: Twenty adult IMN patients and fourteen healthy subjects were included in the study. The basic indexes of a routine biochemical examination and coagulative function were determined. The plasma levels of MPs were detected by flow cytometry, and TF activity of MPs was examined using an assay kit. The plasma levels of lipopolysaccharide (LPS) were measured by an enzyme-linked immunosorbent assay.

Results: Total circulating MPs were not increased in patients with IMN compared with healthy controls. Circulating CD14/TFMPs were significantly increased in IMN patients, but this achieved significance was not observed in CD41/TFMPs between the two groups. Interestingly, the circulating TF-positive MPs were increased significantly. Plasma MPs TF assays revealed high procoagulant activity, which was positively associated with the D-dimer level in IMN. In addition, circulating LPS in IMN patients were significantly higher than those in the controls. Furthermore, after two hours' incubation with healthy whole blood, LPS enhanced the release of circulating TF-positive MPs and the TF activity of MPs.

Conclusion: Increased circulating LPS may mediate the release of monocyte-derived TF-positive MPs, which further contributes to the hypercoagulable state in IMN patients. These findings provide an additional mechanism by which patients with IMN have a higher risk of thromboembolic complication.
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http://dx.doi.org/10.5551/jat.46284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545459PMC
June 2019

Platelet Microparticles Mediate Glomerular Endothelial Injury in Early Diabetic Nephropathy.

J Am Soc Nephrol 2018 11 19;29(11):2671-2695. Epub 2018 Oct 19.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; and.

Background: Glomerular endothelium dysfunction, which plays a crucial role in the pathogenesis of early diabetic nephropathy, might be caused by circulating metabolic abnormalities. Platelet microparticles, extracellular vesicles released from activated platelets, have recently emerged as a novel regulator of vascular dysfunction.

Methods: We studied the effects of platelet microparticles on glomerular endothelial injury in early diabetic nephropathy in rats with streptozotocin-induced diabetes and primary rat glomerular endothelial cells. Isolated platelet microparticles were measured by flow cytometry.

Results: Plasma platelet microparticles were significantly increased in diabetic rats, an effect inhibited in aspirin-treated animals. In cultured glomerular endothelial cells, platelet microparticles induced production of reactive oxygen species, decreased nitric oxide levels, inhibited activities of endothelial nitric oxide synthase and SOD, increased permeability of the glomerular endothelium barrier, and reduced thickness of the endothelial surface layer. Conversely, inhibition of platelet microparticles by aspirin improved glomerular endothelial injury. Further analysis showed that platelet microparticles activated the mammalian target of rapamycin complex 1 (mTORC1) pathway in glomerular endothelial cells; inhibition of the mTORC1 pathway by rapamycin or raptor siRNA significantly protected against microparticle-induced glomerular endothelial injury and . Moreover, platelet microparticle-derived chemokine ligand 7 (CXCL7) contributed to glomerular endothelial injury, and antagonizing CXCL7 using CXCL7-neutralizing antibody or blocking CXCL7 receptors with a competitive inhibitor of CXCR1 and CXCR2 dramatically attenuated such injury.

Conclusions: These findings demonstrate a pathogenic role of platelet microparticles in glomerular endothelium dysfunction, and suggest a potential therapeutic target, CXCL7, for treatment of early diabetic nephropathy.
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http://dx.doi.org/10.1681/ASN.2018040368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218868PMC
November 2018

Factorization machines and deep views-based co-training for improving answer quality prediction in online health expert question-answering services.

J Biomed Inform 2018 11 18;87:21-36. Epub 2018 Sep 18.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China. Electronic address:

In online health expert question-answering (HQA) services, it is significant to automatically determine the quality of the answers. There are two prominent challenges in this task. First, the answers are usually written in short text, which makes it difficult to absorb the text semantic information. Second, it usually lacks sufficient labeled data but contains a huge amount of unlabeled data. To tackle these challenges, we propose a novel deep co-training framework based on factorization machines (FM) and deep textual views to intelligently and automatically identify the quality of HQA systems. More specifically, we exploit additional domain-specific semantic information from domain-specific word embeddings to expand the semantic space of short text and apply FM to excavate the non-independent interaction relationships among diverse features within individual views for improving the performance of the base classifier via co-training. Our learned deep textual views, the convolutional neural networks (CNN) view which focuses on extracting local features using convolution filters to locally model short text and the dependency-sensitive convolutional neural networks (DSCNN) view which focuses on capturing long-distance dependency information within the text to globally model short text, can then overcome the challenge of feature sparseness in the short text answers from the doctors. The developed co-training framework can effectively mine the highly non-linear semantic information embedded in the unlabeled data and expose the highly non-linear relationships between different views, which minimizes the labeling effort. Finally, we conduct extensive empirical evaluations and demonstrate that our proposed method can significantly improve the predictive performance of the answer quality in the context of HQA services.
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http://dx.doi.org/10.1016/j.jbi.2018.09.011DOI Listing
November 2018

Lipoprotein(a) accelerated the progression of atherosclerosis in patients with end-stage renal disease.

BMC Nephrol 2018 08 2;19(1):192. Epub 2018 Aug 2.

Institute of Nephrology, Zhong Da Hospital, Medical School of Southeast University, NO. 87, Ding Jia Qiao Road, Nang Jing City, 210009, Jiang Su Province, China.

Background: Increased plasma level of lipoprotein(a) (Lpa) is a risk factor of cardiovascular diseases. This study aimed to explore the role of Lpa in the progression of atherosclerosis in patients with end-stage renal disease (ESRD) and to investigate whether its potential mechanism is mediated by CXC chemokine ligand 16 (CXCL16) and low-density lipoprotein receptor (LDLr).

Methods: This is a retrospective clinical study. From January 2015 to April 2016, forty-six ESRD patients from Danyang First People's Hospital were investigated. The patients were grouped according to their plasma Lpa levels: control group (Lpa < 300 mg/l, n = 23) and high Lpa group (Lpa ≥ 300 mg/l, n = 23). ESRD Patients with acute infective diseases, cancer, and/or chronic active hepatitis were excluded. Biochemical indexes and lipid profiles of the patients were measured. Surgically removed tissues from the radial arteries of ESRD patients receiving arteriovenostomy were used for the preliminary evaluation of atherosclerosis. Haematoxylin-eosin (HE) and filipin staining were used to observe foam cell formation. Protein expression levels of Lpa, CXCL16, and LDLr were detected by immunohistochemistry staining and immunofluorescent staining.

Results: There was more foam cell formation and cholesterol accumulation in the radial arteries of the high Lpa group than in those of the control group. Furthermore, the expression levels of Lpa, CXCL16, and LDLr were significantly increased in the radial arteries of the high Lpa group. Correlation analyses showed that the protein expression levels of Lpa (r = 0.72, P < 0.01), LDLr (r = 0.54, P < 0.01), and CXCL16 (r = 0.6, P < 0.01) in the radial arteries of ESRD patients were positively correlated with the plasma Lpa levels. Further analyses showed that the co-expression of Lpa with LDLr or CXCL16 was increased in the high Lpa group.

Conclusions: High plasma Lpa levels accelerated the progression of atherosclerosis in ESRD through inducing Lpa accumulation in the arteries, which was associated with LDLr and CXCL16. These two lipoproteins could both be major lipoprotein components that regulate the entry of Lpa into arterial cells.
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http://dx.doi.org/10.1186/s12882-018-0986-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090984PMC
August 2018

Activation of the CXCL16/CXCR6 pathway promotes lipid deposition in fatty livers of apolipoprotein E knockout mice and HepG2 cells.

Am J Transl Res 2018 15;10(6):1802-1816. Epub 2018 Jun 15.

Centre for Nephrology, University College London (UCL) Medical School, Royal Free Campus UK.

Non-alcoholic fatty liver disease (NAFLD), characterised by early lipid accumulation and subsequent inflammation in the liver, is becoming a worldwide challenge due to its increasing prevalence in developing and developed countries. This study aimed to investigate the role of CXC chemokine ligand 16 (CXCL16) and its receptor CXC chemokine receptor 6 (CXCR6) in NAFLD under inflammation. We used IL-1β stimulation in human hepatoblastoma cell line (HepG2) for studies and casein injection in apolipoprotein E knockout mice to induce inflammatory stress. The effects of inflammation on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expression of molecules involved in CXCL16/CXCR6 pathway and extracellular matrix (ECM) were examined by real-time polymerase chain reaction (PCR) and Western blotting. The fluorescence intensity of reactive oxygen species (ROS) was assessed by flow cytometry. Results showed that significantly elevated levels of serum amyloid protein A in casein-injected mice confirmed the successful induction of inflamed NAFLD model. Inflammation significantly increased lipid accumulation in livers compared with the high-fat diet group and the controls. Furthermore, inflammation increased the expression of CXCL16, CXCR6, and adisintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in livers, accompanied with increased ECM expression and ROS production. These effects were further confirmed by studies. Interestingly, CXCL16 gene knockdown in HepG2 cells induced by CXCL16 siRNA resulted in decreased lipid accumulation, ECM excretion, and ROS production. These findings demonstrated that inflammation-mediated activation of CXCL16/CXCR6 is involved in the progression of NAFLD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038063PMC
June 2018

A new species of the genus with setaceous mouthparts and forelegs from southern China (Ephemeroptera, Ephemerellidae).

Zookeys 2017 6(714):33-46. Epub 2017 Nov 6.

The Key Laboratory of Jiangsu Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, China.

The nymph and reared male and female of a new ephemerellid species, which was collected from southern China and named Zhou, , are described. The nymph is unique because of its long and dense setae on labrum, mandibles, maxillae, labium, and forelegs as well as the elongated segments II of labial palpi and expanded paraglossae. The male can be differentiated from close relatives by its larger penis lobes with dorsolateral projections, and the more pigmented tergum IV and caudal filaments. The nymph described in this paper represents a new adaptive and ecological type in the family Ephemerellidae.
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http://dx.doi.org/10.3897/zookeys.714.13646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784217PMC
November 2017

The synergic effect of BRAF mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma.

Endocr J 2018 Jan 26;65(1):113-120. Epub 2017 Oct 26.

Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.

The purpose of this study is to evaluate the potential synergic effect of BRAF mutation and multifocality on central lymph nodes metastasis (CLNM) in the patients with unilateral papillary thyroid carcinoma (PTC). We enrolled 413 patients with unilateral PTCs who accepted prophylactic unilateral or bilateral central lymph node dissection (LND). Univariate and multivariate analyses were made to determine the association between related factors and CLNM. Then, all patients were divided into 4 groups based on their status of BRAF mutation and multifocality. Relative excess risk of interaction (RERI), attributable proportion (AP) of interaction and synergy index (SI) were applied to evaluate the interactive effect of these two factors on CLNM. Results showed that BRAF mutation and multifocality were independent risk factors for CLNM. A further study revealed that unilateral PTCs accompanying multifocality with BRAF mutation had the highest incidence of CLNM compared with other subgroups. Besides, RERI was 4.323 (95% CI = 1.276-7.369), AP was 0.523 (95% CI = 0.364-0.682) and SI was 2.469 (95% CI = 1.607 to 3.794), indicating a significant additive interaction of BRAF mutation and multifocality on CLNM. The present study has confirmed that BRAF mutation and multifocality are risk factors for CLNM in unilateral PTC. Additionally, unilateral PTC patients accompanying multifocality with BRAF mutation may have an increased risk of CLNM in clinically negative CLNM.
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http://dx.doi.org/10.1507/endocrj.EJ17-0110DOI Listing
January 2018

De novo transcriptome of the mayfly Cloeon viridulum and transcriptional signatures of Prometabola.

PLoS One 2017 21;12(6):e0179083. Epub 2017 Jun 21.

The Key Laboratory of Jiangsu Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.

Mayflies (Ephemeroptera) display many primitive characters and a unique type of metamorphosis (Prometabola). However, information on the genomes and transcriptomes of this insect group is limited. The RNA sequencing study presented here generated the first de novo transcriptome assembly of Cloeon viridulum (Ephemeroptera: Baetidae), and compared gene expression signatures among the young larva (YL), mature larva (ML), subimago (SI), and imago (IM) stages of this mayfly. The transcriptome, based on 88 Gb of sequence data, comprised a set of 81,185 high quality transcripts. The number of differentially expressed genes (DEGs) in YL vs. ML, ML vs. SI, and SI vs. IM, was 4,825, 1,584, and 1,278, respectively, according to the reads per kilobase of transcript per million mapped reads analysis, assuming a false discovery rate <0.05 and a fold change >2. Gene enrichment analysis revealed that these DEGs were enriched in the "chitin metabolic process", "germ cell development", "steroid hormone biosynthesis", and "cutin, suberine, and wax biosynthesis" pathways. Finally, the expression pattern of a selected group of candidate signature genes for Prometabola, including vestigial, methoprene-tolerant, wingless, and broad-complex were confirmed by quantitative real time-PCR analysis. The Q-PCR analysis of larval, subimaginal, and imaginal stages of C. viridulum suggests that the development of mayflies more closely resembles hemimetamorphosis than holometamorphosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179083PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479533PMC
October 2017

A deep learning approach for predicting the quality of online health expert question-answering services.

J Biomed Inform 2017 07 9;71:241-253. Epub 2017 Jun 9.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China. Electronic address:

Recently, online health expert question-answering (HQA) services (systems) have attracted more and more health consumers to ask health-related questions everywhere at any time due to the convenience and effectiveness. However, the quality of answers in existing HQA systems varies in different situations. It is significant to provide effective tools to automatically determine the quality of the answers. Two main characteristics in HQA systems raise the difficulties of classification: (1) physicians' answers in an HQA system are usually written in short text, which yields the data sparsity issue; (2) HQA systems apply the quality control mechanism, which refrains the wisdom of crowd. The important information, such as the best answer and the number of users' votes, is missing. To tackle these issues, we prepare the first HQA research data set labeled by three medical experts in 90days and formulate the problem of predicting the quality of answers in the system as a classification task. We not only incorporate the standard textual feature of answers, but also introduce a set of unique non-textual features, i.e., the popular used surface linguistic features and the novel social features, from other modalities. A multimodal deep belief network (DBN)-based learning framework is then proposed to learn the high-level hidden semantic representations of answers from both textual features and non-textual features while the learned joint representation is fed into popular classifiers to determine the quality of answers. Finally, we conduct extensive experiments to demonstrate the effectiveness of including the non-textual features and the proposed multimodal deep learning framework.
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http://dx.doi.org/10.1016/j.jbi.2017.06.012DOI Listing
July 2017

Synthesis and characterization of ultralong SiC nanowires with unique optical properties, excellent thermal stability and flexible nanomechanical properties.

Sci Rep 2017 06 7;7(1):3011. Epub 2017 Jun 7.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin, 150001, P.R. China.

Several-millimeter long SiC nanowires (NWs) with unique optical properties, excellent thermal stability and flexible nanomechanical properties were synthesized using a simple method with silicon and phenolic resin as the raw materials. The SiC NWs displayed special optical properties that were attributed to their large size and Al-doping. They displayed broad green emission at 527.8 nm (2.35 eV) and purple emission concentrated at 438.9 nm (2.83 eV), in contrast to the other results, and the synthesized SiC NWs could also remain relatively stable in air up to 1000 °C indicating excellent thermal stability. The Young's moduli of the SiC NWs with a wide range of NW diameters (215-400 nm) were measured using an in situ nanoindentation method with a hybrid scanning electron microscopy/scanning probe microscopy (SEM/SPM) system for the first time. The results suggested that the values of the Young's modulus of the SiC NWs showed no clear size dependence, and the corresponding Young's moduli of the SiC NWs with diameters of 215 nm, 320 nm, and 400 nm were approximately 559.1 GPa, 540.0 GPa and 576.5 GPa, respectively. These findings provide value and guidance for studying and understanding the properties of SiC nanomaterials and for expanding their possible applications.
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http://dx.doi.org/10.1038/s41598-017-03588-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462820PMC
June 2017

A Topology Control Strategy with Reliability Assurance for Satellite Cluster Networks in Earth Observation.

Sensors (Basel) 2017 Feb 23;17(3). Epub 2017 Feb 23.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China.

This article investigates the dynamic topology control problemof satellite cluster networks (SCNs) in Earth observation (EO) missions by applying a novel metric of stability for inter-satellite links (ISLs). The properties of the periodicity and predictability of satellites' relative position are involved in the link cost metric which is to give a selection criterion for choosing the most reliable data routing paths. Also, a cooperative work model with reliability is proposed for the situation of emergency EO missions. Based on the link cost metric and the proposed reliability model, a reliability assurance topology control algorithm and its corresponding dynamic topology control (RAT) strategy are established to maximize the stability of data transmission in the SCNs. The SCNs scenario is tested through some numeric simulations of the topology stability of average topology lifetime and average packet loss rate. Simulation results show that the proposed reliable strategy applied in SCNs significantly improves the data transmission performance and prolongs the average topology lifetime.
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http://dx.doi.org/10.3390/s17030445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375731PMC
February 2017

Activation of the CXCL16/CXCR6 Pathway by Inflammation Contributes to Atherosclerosis in Patients with End-stage Renal Disease.

Int J Med Sci 2016 20;13(11):858-867. Epub 2016 Oct 20.

Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Chronic inflammation plays a critical role in the progression of atherosclerosis (AS). This study aimed to determine the effects of the CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on cholesterol accumulation in the radial arteries of end-stage renal disease (ESRD) patients with concomitant microinflammation and to further investigate the potential effects of the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R). Forty-three ESRD patients were divided into the control group (n=17) and the inflamed group (n=26) based on plasma C-reactive protein (CRP) levels. Biochemical indexes and lipid profiles of the patients were determined. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used for preliminary evaluation of AS. Haematoxylin-eosin (HE) and Filipin staining were performed to assess foam cell formation. CXCL16/CXCR6 pathway-related protein expression, P2X7R protein expression and the expression of monocyte chemotactic protein-1 (MCP-1), tumour necrosis factor-α (TNF-α), and CD68 were detected by immunohistochemical and immunofluorescence staining. Inflammation increased both MCP-1 and TNF-α expression and macrophage infiltration in radial arteries. Additionally, foam cell formation significantly increased in the radial arteries of the inflamed group compared to that of the controls. Further analysis showed that protein expression of CXCL16, CXCR6, disintegrin and metalloproteinase-10 (ADAM10) in the radial arteries of the inflamed group was significantly increased. Furthermore, CXCL16 expression was positively correlated with P2X7R expression in the radial arteries of ESRD patients. Inflammation contributed to foam cell formation in the radial arteries of ESRD patients via activation of the CXCL16/CXCR6 pathway, which may be regulated by P2X7R.
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http://dx.doi.org/10.7150/ijms.16724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118757PMC
March 2017

The nymph and imago of Chinese mayfly Siphlonurus davidi (Navás, 1932).

Zookeys 2016 26(607):37-48. Epub 2016 Jul 26.

The Key Laboratory of Jiangsu Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, China.

The imagos and nymphs of Siphlonurus davidi (Navás, 1932) are described for the first time. The adult has colourful wings and cross veins, the MP is forked asymmetrically at its base, a long cubital area is present with more intercalaries, and it has a relatively simpler penis and larger hindwings compared to its congeners. The venation and genitalia show that it is a plesiomorphic species in the genus. A key to the Asian species of Siphlonurus with coloured wings is provided in conclusion.
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http://dx.doi.org/10.3897/zookeys.607.9159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978025PMC
August 2016

Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to non-alcoholic fatty liver disease.

Liver Int 2016 10 3;36(10):1525-34. Epub 2016 May 3.

Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.

Background: This study aimed to investigate the possible synergistic effects of lipid disorder with renin-angiotensin system (RAS) activation in non-alcoholic fatty liver disease (NAFLD).

Methods: Apolipoprotein E gene-knockout mice, angiotensin II (Ang II) type 1 receptor (AT1) gene-knockout mice and human hepatoblastoma cell line (HepG2) were used for experiments. Lipid accumulation was examined by Filipin staining and intracellular cholesterol quantitative assay. The gene and protein expression of molecules involved in RAS and low-density lipoprotein receptor (LDLr) pathway was examined by real-time PCR, immunofluorescent staining and Western blot.

Results: There was significantly increased expression of RAS components and extracellular matrix (ECM) in livers of high-fat-diet-fed apolipoprotein E gene-knockout mice compared with controls. Upregulation of RAS components was positively associated with increased plasma levels of lipid profile. The in vitro study further confirmed that cholesterol loading increased supernatant renin activity and Ang II level of HepG2 cells, accompanied by increased ECM production that was positively associated with increased expression of intracellular RAS components. Interestingly, Ang II treatment increased lipid accumulation in livers of C57BL/6 mice and HepG2 cells. Furthermore, Ang II treatment increased gene and protein expression of sterol regulatory element-binding protein (SREBP) cleavage activating protein (SCAP), SREBP-2 and LDLr, which were mediated by enhanced SCAP/SREBP-2 complex translocation from endoplasmic reticulum to Golgi. However, LDLr pathway was accordingly downregulated in livers of AT1 gene-knockout C57BL/6 mice or in HepG2 cells treated by telmisartan.

Conclusion: These findings demonstrate that lipid disorder and intrahepatic RAS activation synergistically accelerate NAFLD progression.
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http://dx.doi.org/10.1111/liv.13131DOI Listing
October 2016

Inflammatory stress induces lipid accumulation in multi-organs of db/db mice.

Acta Biochim Biophys Sin (Shanghai) 2015 Oct 3;47(10):767-74. Epub 2015 Sep 3.

Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.

Dyslipidemia and chronic inflammation play crucial roles in the progression of diabetes. This study aimed to investigate the effects of inflammatory stress on lipid accumulation in multi-organs in diabetes. Eight-week-old male db/db mice were randomly assigned to inflamed group with alternating day subcutaneous injection of 10% casein or control group with daily injection of distilled water. The lipid profile and plasma levels of inflammatory cytokines were determined using a clinical biochemical assay and enzyme-linked immunosorbent assay. The effects of inflammation on lipid accumulation in target organs were evaluated by hematoxylin-eosin staining, Oil Red O staining, Filipin staining, and a quantitative intracellular cholesterol assay. The protein expressions of low-density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP-cleavage-activating protein (SCAP) in tissues were assessed by immunohistochemical staining and western blotting. Results showed that the serum levels of inflammatory cytokines were significantly elevated in casein-injected mice, suggesting that an inflamed diabetic model was established. Furthermore, the protein expressions of inflammatory cytokines in aortas, livers, kidneys, and intestines were significantly increased in inflamed group compared with control. Whereas the serum levels of lipid moieties in inflamed mice were not different compared with the control, inflammatory stress significantly increased lipid accumulation in aortas, livers, kidneys, and intestines, which coincided with increased protein expressions of LDLr, SREBP-2, and SCAP in these organs of inflamed mice. In conclusion, inflammation induces lipid accumulation in multi-organs of db/db mice from the circulation to peripheral tissues, potentially due to lipid redistribution mediated by the disruption of LDLr feedback regulation.
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http://dx.doi.org/10.1093/abbs/gmv079DOI Listing
October 2015

Dysregulation of low-density lipoprotein receptor contributes to podocyte injuries in diabetic nephropathy.

Am J Physiol Endocrinol Metab 2015 Jun 28;308(12):E1140-8. Epub 2015 Apr 28.

Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing City, Jiangsu Province, China.

Dyslipidemia plays crucial roles in the progression of diabetic nephropathy (DN). This study investigated the effects of high glucose on lipid accumulation in podocytes and explored its underlying mechanisms. Male db/m and db/db mice were fed a normal chow diet for 8 wk. Immortalised mouse podocytes were treated with or without high glucose for 24 h. The changes to the morphology and ultramicrostructures of the kidneys in mice were examined using pathological staining and electron microscopy. Intracellular lipid accumulation was evaluated by Oil Red O staining and a free cholesterol quantitative assay. The expressions of the molecules involved in low-density lipoprotein receptor (LDLr) pathway and podocyte injury were examined using immunofluorescent staining, real-time PCR, and Western blot. There were increased levels of plasma lipid, serum creatinine, and proteinuria in db/db mice compared with db/m mice. Moreover, there was significant mesangial matrix expansion, basement membrane thickening, podocyte foot process effacement, and phenotypic alteration in the db/db group. Additionally, lipid accumulation in the kidneys of db/db mice was increased due to increased protein expressions of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein, and SREBP-2. These effects were further confirmed by in vitro studies. Interestingly, the treatment with LDLr siRNA inhibited lipid accumulation in podocytes and decreased the protein expression of molecules associated with phenotypic alteration in podocytes. High glucose disrupted LDLr feedback regulation in podocytes, which may cause intracellular lipid accumulation and alteration of podocyte phenotype, thereby accelerating DN progression.
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http://dx.doi.org/10.1152/ajpendo.00591.2014DOI Listing
June 2015
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