Publications by authors named "Guosheng Yang"

74 Publications

Compensatory role of endogenous sulfur dioxide in nitric oxide deficiency-induced hypertension.

Redox Biol 2021 Nov 18;48:102192. Epub 2021 Nov 18.

Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address:

Objective: This study aimed to determine the communicational pattern of gaseous signaling molecules sulfur dioxide (SO) and nitric oxide (NO) between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), and elucidate the compensatory role and significance of endogenous SO in the development of hypertension due to NO deficiency.

Approach And Results: Blood pressure was monitored by the tail-cuff and implantable physiological signal telemetry in L-nitro-arginine methyl ester (l-NAME)-induced hypertensive mice, and structural alterations of mouse aortic vessels were detected by the elastic fiber staining method. l-NAME-treated mice showed decreased plasma NO levels, increased SO levels, vascular remodeling, and increased blood pressure, and application of l-aspartate-β-hydroxamate, which inhibits SO production, further aggravated vascular structural remodeling and increased blood pressure. Moreover, in a co-culture system of HAECs and HASMCs, NO from HAECs did not influence aspartate aminotransferase (AAT)1 protein expression but decreased AAT1 activity in HASMCs, thereby resulting in the inhibition of endogenous SO production. Furthermore, NO promoted S-nitrosylation of AAT1 protein in HASMCs and purified AAT1 protein. Liquid chromatography with tandem mass spectrometry showed that the Cys192 site of AAT1 purified protein was modified by S-nitrosylation. In contrast, dithiothreitol or C192S mutations in HASMCs blocked NO-induced AAT1 S-nitrosylation and restored AAT1 enzyme activity.

Conclusion: Endothelium-derived NO inhibits AAT activity by nitrosylating AAT1 at the Cys192 site and reduces SO production in HASMCs. Our findings suggest that SO acts as a compensatory defense system to antagonize vascular structural remodeling and hypertension when the endogenous NO pathway is disturbed.
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http://dx.doi.org/10.1016/j.redox.2021.102192DOI Listing
November 2021

Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/HS Inhibition.

Oxid Med Cell Longev 2021 25;2021:5530907. Epub 2021 Aug 25.

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal HS content and enhanced cystathionine--synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited HS generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/HS pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats.
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http://dx.doi.org/10.1155/2021/5530907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413057PMC
August 2021

Endothelial Cell-Derived SO Controls Endothelial Cell Inflammation, Smooth Muscle Cell Proliferation, and Collagen Synthesis to Inhibit Hypoxic Pulmonary Vascular Remodelling.

Oxid Med Cell Longev 2021 17;2021:5577634. Epub 2021 Apr 17.

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Hypoxic pulmonary vascular remodelling (PVR) is the major pathological basis of aging-related chronic obstructive pulmonary disease and obstructive sleep apnea syndrome. The pulmonary artery endothelial cell (PAEC) inflammation, and pulmonary artery smooth muscle cell (PASMC) proliferation, hypertrophy and collagen remodelling are the important pathophysiological components of PVR. Endogenous sulfur dioxide (SO) was found to be a novel gasotransmitter in the cardiovascular system with its unique biological properties. The study was aimed to investigate the role of endothelial cell- (EC-) derived SO in the progression of PAEC inflammation, PASMC proliferation, hypertrophy and collagen remodelling in PVR and the possible mechanisms. EC-specific aspartic aminotransferase 1 transgenic (EC-AAT1-Tg) mice were constructed . Pulmonary hypertension was induced by hypoxia. Right heart catheterization and echocardiography were used to detect mouse hemodynamic changes. Pathologic analysis was performed in the pulmonary arteries. High-performance liquid chromatography was employed to detect the SO content. Human PAECs (HPAECs) with lentiviruses containing AAT1 cDNA or shRNA and cocultured human PASMCs (HPASMCs) were applied . SO probe and enzyme-linked immunosorbent assay were used to detect the SO content and determine p50 activity, respectively. Hypoxia caused a significant reduction in SO content in the mouse lung and HPAECs and increases in right ventricular systolic pressure, pulmonary artery wall thickness, muscularization, and the expression of PAEC ICAM-1 and MCP-1 and of PASMC Ki-67, collagen I, and -SMA ( < 0.05). However, EC-AAT1-Tg with sufficient SO content prevented the above increases induced by hypoxia ( < 0.05). Mechanistically, EC-derived SO deficiency promoted HPAEC ICAM-1 and MCP-1 and the cocultured HPASMC Ki-67 and collagen I expression, which was abolished by andrographolide, an inhibitor of p50 ( < 0.05). Meanwhile, EC-derived SO deficiency increased the expression of cocultured HPASMC -SMA ( < 0.05). Taken together, these findings revealed that EC-derived SO inhibited p50 activation to control PAEC inflammation in an autocrine manner and PASMC proliferation, hypertrophy, and collagen synthesis in a paracrine manner, thereby inhibiting hypoxic PVR.
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http://dx.doi.org/10.1155/2021/5577634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068783PMC
May 2021

The Gene Family Serves as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 31;11:620126. Epub 2021 Mar 31.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

The cysteine-serine-rich nuclear protein () family has prognostic value for various cancers. However, the association between this proteins and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to determine the prognostic value of the family for patients with ccRCC. Therefore, the gene expression profiling interactive analysis database was used to analyze the mRNA expression of family members () in relation with survival. Combined and independent prognostic values of CSRNPs were evaluated using SurvExpress and multivariate Cox regression analyses, respectively. Potential signaling pathways impacted by were evaluated using Metascape. Associations between the family and immunocyte infiltration were determined from single-sample gene set enrichment analysis. Both cBioPortal and MethSurv were used to explore whether genomic and epidemic alterations might influence prognosis. We found that when both and had a low expression, patients with ccRCC had a worse overall survival (OS). Therefore, a prognostic signature was constructed as follows: risk score = -0.224 × exp + 0.820 × exp - 1.428 × exp . We found that OS was worse in patients from the high- than from the low-risk groups (AUC = 0.69). Moreover, this signature was an independent predictor after adjusting for clinical features. Functional enrichment analysis positively associated CSRNPs with the acute inflammatory response and humoral immune response pathways. This was validated by correlating each with 28 types of immunocytes in tumor and normal tissues. A higher expression of and was associated with a better prognosis in both the high- and low-mutant burden groups. Cg19538674, cg07772537, and cg07811002 of , , and , respectively, were the predominant DNA methylation sites affecting OS. The gene family signature may serve as a prognostic biomarker for predicting OS in patients with ccRCC. The association between and immune infiltration might offer future clinical treatment options.
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http://dx.doi.org/10.3389/fonc.2021.620126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045970PMC
March 2021

Rapid analysis of Np and Pu isotopes in small volume urine by SF-ICP-MS and ICP-MS/MS.

Anal Chim Acta 2021 May 20;1158:338431. Epub 2021 Mar 20.

National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage, Chiba, 263-8555, Japan.

Internal contamination with alpha-particle emitting actinides, such as Np, Pu, Pu, is likely to bring a large amount of dose to the tissues of persons even if the intake amount is small. To provide timely information for prompt decision-making in radiation emergency therapy, we developed a simple and rapid method for urinary bioassay to determine ultra-trace Np and Pu isotopes using SF-ICP-MS and ICP-MS/MS. To avoid polyatomic interferences and tailing effects from U, Np and Pu isotopes were collected after removing U effectively using a simple single chromatographic column packed with 2 mL AG MP-1M anion exchange resin, exhibiting a high decontamination factor of 10 for U. The overall chemical fractionation between Np and Pu for the whole analytical procedure was 0.974 ± 0.064 (k = 2), allowing us to measure Np and Pu isotopes using Pu as a yield tracer with yields of 76 ± 5%. Using ICP-MS/MS with low background provided the method detection limits for Np, Pu, Pu, and Pu of 0.025, 0.025, 0.015, and 0.020 fg mL, respectively, for 20 mL of urine sample. Those were comparable to detection limits of SF-ICP-MS with high sensitivity. Subsequently, three urine reference materials with Pu spike, provided by the Association for the PROmotion of Quality COntrol in RADiotoxicological Analysis (PROCORAD), France, were analyzed by the developed method and the conventional alpha spectrometry technique for validation. Finally, the developed method was successfully employed to measure the contamination level of Np, Pu, Pu, and Pu in urine samples collected during decorporation therapy using DTPA, after a Pu inhalation exposure accident in Japan. The high throughput (9 h for 12 samples), simplicity, low cost, and high sensitivity of the method will allow greater numbers of related laboratories to be involved in screening activities for unexpected actinide exposure, such as in the case of a large scale radiological disaster.
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http://dx.doi.org/10.1016/j.aca.2021.338431DOI Listing
May 2021

Study protocol for a single-centre non-inferior randomised controlled trial on a novel three-dimensional matrix positioning-based cognitive fusion-targeted biopsy and software-based fusion-targeted biopsy for the detection rate of clinically significant prostate cancer in men without a prior biopsy.

BMJ Open 2021 02 5;11(2):e041427. Epub 2021 Feb 5.

Department of Urology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Introduction: The classical pathway for diagnosing prostate cancer is systematic 12-core biopsy under the guidance of transrectal ultrasound, which tends to underdiagnose the clinically significant tumour and overdiagnose the insignificant disease. Another pathway named targeted biopsy is using multiparametric MRI to localise the tumour precisely and then obtain the samples from the suspicious lesions. Targeted biopsy, which is mainly divided into cognitive fusion method and software-based fusion method, is getting prevalent for its good performance in detecting significant cancer. However, the preferred targeted biopsy technique in detecting clinically significant prostate cancer between cognitive fusion and software-based fusion is still beyond consensus.

Methods And Analysis: This trial is a prospective, single-centre, randomised controlled and non-inferiority study in which all men suspicious to have clinically significant prostate cancer are included. This study aims to determine whether a novel three-dimensional matrix positioning cognitive fusion-targeted biopsy is non-inferior to software-based fusion-targeted biopsy in the detection rate of clinically significant cancer in men without a prior biopsy. The main inclusion criteria are men with elevated serum prostate-specific antigen above 4-20 ng/mL or with an abnormal digital rectal examination and have never had a biopsy before. A sample size of 602 participants allowing for a 10% loss will be recruited. All patients will undergo a multiparametric MRI examination, and those who fail to be found with a suspicious lesion, with the anticipation of half of the total number, will be dropped. The remaining participants will be randomly allocated to cognitive fusion-targeted biopsy (n=137) and software-based fusion-targeted biopsy (n=137). The primary outcome is the detection rate of clinically significant prostate cancer for cognitive fusion-targeted biopsy and software-based fusion-targeted biopsy in men without a prior biopsy. The clinically significant prostate cancer will be defined as the International Society of Urological Pathology grade group 2 or higher.

Ethics And Dissemination: Ethical approval was obtained from the ethics committee of Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. The results of the study will be disseminated and published in international peer-reviewed journals.

Trial Registration Number: ClinicalTrials.gov Registry (NCT04271527).
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http://dx.doi.org/10.1136/bmjopen-2020-041427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925935PMC
February 2021

CRISPR-Cas13-Mediated Knockdown of lncRNA-GACAT3 Inhibited Cell Proliferation and Motility, and Induced Apoptosis by Increasing p21, Bax, and E-Cadherin Expression in Bladder Cancer.

Front Mol Biosci 2020 18;7:627774. Epub 2021 Jan 18.

The Second School of Clinical Medicine, Southern Medical University Affiliated Guangdong Second Provincial General Hospital, Southern Medical University, Guangzhou, China.

The current study is to investigate the expression pattern and biological function of long non-coding RNA Focally gastric cancer-associated transcript3 (GACAT3) in bladder cancer. Real-time quantitative qPCR was used to detect the expression level of GACAT-3 in tumor tissues and paired normal tissues. Human bladder cancer T24 and 5637 cell lines were transiently transfected with specific CRISPR-Cas13 or negative control CRISPR-Cas13. Cell migration, proliferation, and apoptosis were measured by using wound healing assay CCK-8 assay and Caspase-3 ELISA assay, respectively. The expression changes of p21, Bax, and E-cadherin after knockdown of GACAT3 were detected by using Western blot. The results demonstrated that GACAT3 was up-regulated in bladder cancer tissues than that in the paired normal tissues. Inhibition of cell proliferation, increased apoptosis, and decreased motility were observed in T24 and 5637 cell lines transfected by CRISPR-Cas13 targeting GACAT3. Downregulation of GACAT3 increased p21, Bax, and E-cadherin expression and silencing these genes could eliminate the phenotypic changes induced by knockdown of GACAT3. A ceRNA mechanism for GACAT3 was also revealed. By using CRISPR-Cas13 biotechnology, we suggested that GACAT3 may be a novel target for diagnosis and treatment of bladder cancer.
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http://dx.doi.org/10.3389/fmolb.2020.627774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848205PMC
January 2021

An Improved Passive CR-39-Based Direct Rn/Rn Progeny Detector.

Int J Environ Res Public Health 2020 11 18;17(22). Epub 2020 Nov 18.

Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki 036-8564, Japan.

An improved passive CR-39-based direct Rn/Rn progeny detector with 3 detection channels was designed and tested in this study to measure and calculate equilibrium equivalent concentration (EEC) of both Rn and Rn without the equilibrium factor. A theoretical model was established to calculate the EEC with optimization. Subsequently, an exposure experiment was carried out to test the performance of this detector, and we compared the chamber experiment and the theoretical model by estimating and measuring various parameters. The deposition flux of progeny derived from the prediction agreed well with the value measured in the exposure chamber. The energy-weighted net track density (NTD) measured by this detector is much more reliable to reflect the linear relation between NTD and time-integrated EEC. Since the detector is sensitive to the exposure environmental condition, it is recommended to apply the detector to measure the EEC after its calibration in a typical indoor environment.
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http://dx.doi.org/10.3390/ijerph17228569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699185PMC
November 2020

A novel method for 3D face symmetry reference plane based on weighted Procrustes analysis algorithm.

BMC Oral Health 2020 11 11;20(1):319. Epub 2020 Nov 11.

Center of Digital Dentistry, Peking University School and Hospital of Stomatology, No.22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China.

Background: We aimed to establish a novel method, using the weighted Procrustes analysis (WPA) algorithm, which assigns weight to facial anatomical landmarks, to construct a three-dimensional facial symmetry reference plane (SRP) for mandibular deviation patients.

Methods: Three-dimensional facial SRPs were independently extracted from 15 mandibular deviation patients using both our WPA algorithm and the standard PA algorithm. A reference plane was defined to serve as the ground truth. To determine whether the WPA SRP or the PA SRP was closer to the ground truth, we measured the position error of mirrored landmarks, the facial asymmetry index (FAI) error, and the angle error for the global face and each facial third partition.

Results: The average angle error between the WPA SRP and the ground truth was 1.66 ± 0.81°, which was smaller than that between the PA SRP and the ground truth. The position error of the mirrored landmarks constructed using the WPA algorithm in the global face (3.64 ± 1.53 mm) and each facial partition was lower than that constructed using the PA algorithm. The average FAI error of the WPA SRP was - 7.77 ± 17.02 mm, which was smaller than that of the PA SRP.

Conclusions: This novel automatic algorithm, based on weighted anatomic landmarks, can provide a more adaptable SRP than the standard PA algorithm when applied to severe mandibular deviation patients and can better simulate the diagnosis strategies of clinical experts.
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http://dx.doi.org/10.1186/s12903-020-01311-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659067PMC
November 2020

Experimental study on the mechanical properties of Guiyang red clay considering the meso micro damage mechanism and stress path.

Sci Rep 2020 Oct 15;10(1):17449. Epub 2020 Oct 15.

Civil Engineering and Architecture College of Wuyi University, Wuyishan, 354300, Fujian, China.

This study investigated the macroscopic physical and mechanical properties of Guiyang red clay during surcharge loading, lateral excavation and lateral unloading with axial loading, and clarified the failure mechanism of microstructure before and after shear under different stress paths of CTC, RTC and TC. Consolidated undrained triaxial shear permeability, SEM scanning, XRF fluorescence spectrum analysis and XRD diffraction tests were conducted to simulate the actual engineering conditions. The stress-strain curve, shear strength, pore water pressure variation rule and macroscopic failure mode of soil samples under different stress paths were analysed. In addition, Image Pro Plus 6.0 and PCAS were used to study the relationship between the macro mechanical properties and micro microstructure failure under different stress paths. The stress-strain curves from CTC, RTC and TC in CU tests were different, with the peak values of shear stress under the three stress paths being P-increasing, equal P-path and P-decreasing path. Moreover, the internal friction angle and cohesion of the increasing P path were higher than those of equal P path and decreasing P path, hence, the influence of stress paths on the cohesion is greater than that of internal friction angle. The pore water pressure is strongly dependent on the stress path, and the variation characteristics of pore water pressure are consistent with the change in the law of the stress-strain curve. Under the same confining pressure in the P-increasing path, the shear failure zone runs through the whole soil sample, and the shear failure zone is significant, whereas under the condition of the P-reducing path, the shear failure angle of soil sample is about 65°, 55° and 45°, and in the equal P path, the soil sample is dominated by the confining pressure, with no obvious microcrack on the surface of the soil sample. The difference is that the distribution of pores in the path of increasing P and equal P is directional, and the anisotropy rate is small, while the distribution of pores in soil samples with shear failure and before shear is random and the anisotropy rate is high.
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http://dx.doi.org/10.1038/s41598-020-72465-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562745PMC
October 2020

Gambogic acid inhibits proliferation and induces apoptosis of human acute T‑cell leukemia cells by inducing autophagy and downregulating β‑catenin signaling pathway: Mechanisms underlying the effect of Gambogic acid on T‑ALL cells.

Oncol Rep 2020 10 11;44(4):1747-1757. Epub 2020 Aug 11.

Department of General Practice, Wangjiangshan Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.

The main active compound of Garcinia hanburyi (referred to as gamboge) is gambogic acid (GA), which has long been a Chinese herbal medicine for treating several types of cancer. However, the potential therapeutic role and mechanisms of GA in T‑cell acute lymphoblastic leukemia (T‑ALL) remain unclear. In the present study, the effects of GA on proliferation, cell cycle, apoptosis, and autophagy in T‑ALL cell lines were investigated. The possible mechanisms underlying GA activity were also examined. The results showed that GA inhibited proliferation, induced apoptosis, and activated autophagy in T‑ALL cell lines (Jurkat and Molt‑4 cells). Findings confirmed that GA has an antileukemia effect against peripheral blood lymphocyte cells in patients with ALL. GA inhibited phospho‑GSK3β S9 (p‑GSK3β S9) protein levels to inactivate Wnt signaling and suppress β‑catenin protein levels. In addition, the inhibitory effect of GA on T‑ALL was reversed by overexpression of β‑catenin. Thus, GA can inhibit the growth and survival of T‑ALL cells. GA also had antileukemic activity, at least in part, through the downregulation of the Wnt/β‑catenin signaling pathway.
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http://dx.doi.org/10.3892/or.2020.7726DOI Listing
October 2020

Background and fingerprint characteristics of anthropogenic U andCs in soil and road dust samples collected from Beijing and Zhangjiakou, China.

Chemosphere 2021 Jan 12;263:127909. Epub 2020 Aug 12.

Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

U has attracted more attention as an environmental tracer in recent years. However, in-depth study of U in terrestrial environments is still rare in China. Data on U and Cs concentrations in soil and road dust samples collected from Beijing and Zhangjiakou, China were obtained to demonstrate the background and distinct characteristics of anthropogenic U and Cs. U and Cs were detected in the range of (1.10-7.90) × 10 atoms g and below the method limits of detection to 5.30 Bq kg. A clear characteristic was observed in road dust, where U concentrations increased with decreasing of sample particle size. Soil samples showed an irregular characteristic, but the highest U concentrations were observed in particle size fraction of <0.053 mm in both samples. This phenomenon was caused by U chemical properties, higher specific surface areas and organic compounds in fine particles. Anthropogenic radionuclides fingerprint characteristics in <0.053 mm samples were specially discussed. U/U atom ratios were detected in the range of (0.627-3.38) × 10. A weak correlation between anthropogenic U and natural U isotopes were observed. The intermediate correlation between U and Cs indicated somewhat distinct migration behavior of these two radionuclides in soil after release to the environment. The released amount of U from global fallout during the period of atmospheric nuclear weapons testing was roughly estimated to be 1300 ± 448 kg. These results could be used as fingerprint information for anthropogenic U migration behavior and tracer application in environment.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127909DOI Listing
January 2021

CAESIUM RETENTION CHARACTERISTICS OF KNIFC-PAN RESIN FROM RIVER WATER.

Radiat Prot Dosimetry 2020 Sep;190(3):320-323

Institute of Radiation Emergency Medicine, Hirosaki University, Hirosaki 036-8203, Japan.

The caesium retention characteristics of a potassium-nickel hexacyanoferrate resin in a polyacrylnitrile (KNiFC-PAN) matrix were tested in fresh water over the range of 2.5-400 mL min-1. The experimental setup used 2 mL resin and 4-L aliquots of freshwater samples. The results showed nearly 100% retention at speeds below 10 mL min-1, above 80% up to 100 mL min-1, and approached 50% at 400 mL min-1. Using 100 mL min-1 flow rate and KNiFC-PAN resin in a well-type HPGe detector, the minimum detectable concentration was reduced to 3 mBq kg-1 for 4-L aliquots of water samples from the previous 15 mBq kg-1 achieved by Powdex ion-exchange resin and a planar type HPGe detector.
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http://dx.doi.org/10.1093/rpd/ncaa109DOI Listing
September 2020

Simple and sensitive determination of radium-226 in river water by single column-chromatographic separation coupled to SF-ICP-MS analysis in medium resolution mode.

J Environ Radioact 2020 Sep 25;220-221:106305. Epub 2020 May 25.

Stake Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai, 200241, China.

This article describes a novel and simple method to measure ultra-trace Ra in river water samples at fg L (mBq L) levels as a means for surveying Ra in an unintended contamination in river water. To simplify the procedure, a single column was used for separation and purification; 10 mL of AG 50W-X8 resin was packed into a 10 mL Eppendorf pipette tip, which was used as a separation column. A 500 mL sample solution was loaded, and interfering elements were removed with 80 mL 4 M HCl in 20% ethanol. Subsequently, Ra together with Ba was eluted by 20 mL 5 M HNO prior to SF-ICP-MS analysis; this allows the naturally existing Ba in water samples to be employed as a yield tracer for Ra analysis. Using the medium mode of SF-ICP-MS, the instrumental detection limit of 380 fg L (10 mBq L) was obtained. An extremely low method detection limit of 0.46 fg L (0.02 mBq L) was achieved with 500-fold pre-concentration. Finally, the developed technique was applied to analyze natural water samples collected from Japanese rivers, in which the Ra concentrations varied in the range of 0.7-49.6 fg L (0.03-1.82 mBq L).
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http://dx.doi.org/10.1016/j.jenvrad.2020.106305DOI Listing
September 2020

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation.

Clin Sci (Lond) 2019 10;133(20):2045-2059

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear.

Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein.

Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling.

Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.
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http://dx.doi.org/10.1042/CS20190514DOI Listing
October 2019

Febuxostat is superior to allopurinol in delaying the progression of renal impairment in patients with chronic kidney disease and hyperuricemia.

Int Urol Nephrol 2019 Dec 23;51(12):2273-2283. Epub 2019 Oct 23.

Department of Nephrology, The Fifth Hospital of Wuhan, 122 Xianzheng Street, Wuhan, 430050, China.

Purpose: This study aimed to compare efficacy of renal-protective function between febuxostat and allopurinol in patients with chronic kidney disease (CKD) and hyperuricemia (HUA).

Methods: Totally 152 CKD stage 2-3 patients complicated with HUA were recruited. According to their uric acid-lowering therapy, there were 67 patients included in febuxostat group and 85 in allopurinol group, respectively. Estimated glomerular filtration rate (eGFR), serum creatinine (Scr), 24-h proteinuria, serum uric acid (SUA) were measured at M0, M1, M3 and M6 after the treatment. Primary outcome was proportion of patients showing ≥ 10% decline in eGFR from baseline at M6.

Results: The eGFR at M6 was numerically higher at M6 and eGFR change (M6-M0) was increased in febuxostat group compared with allopurinol group. Most importantly, the proportion of patients showing a ≥ 10% decline in eGFR from baseline at M6 was reduced in febuxostat group compared with allopurinol group. Multivariate logistic regression analyses further validated that febuxostat vs. allopurinol was an independent predictor for reduced risk of eGFR decline ≥ 10% from baseline. Besides, SUA change (M6-M0) was decreased, but Scr change (M6-M0) and 24-h proteinuria change (M6-M0) were similar in febuxostat group compared with allopurinol group.

Conclusions: Febuxostat presents a superior effect in delaying renal impairment progression compared with allopurinol in CKD patients complicated with HUA.
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http://dx.doi.org/10.1007/s11255-019-02318-8DOI Listing
December 2019

Overexpression of thymosin β10 correlates with disease progression and poor prognosis in bladder cancer.

Exp Ther Med 2019 Nov 13;18(5):3759-3766. Epub 2019 Sep 13.

Department of Urology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510317, P.R. China.

Thymosin β10 (TMSB10) has been found to be overexpressed and function as an oncogene in several types of cancer. However, there have been limited reports on the role of TMSB10 in bladder cancer (BCa). In the present study, reverse transcription-quantitative PCR was used to quantify the expression of in BCa cell lines, clinical specimens and their corresponding control samples. The protein expression of TMSB10 was also examined in archived tissues from 101 patients with pathologically confirmed BCa by immunohistochemistry. Univariate and multivariate Cox regression models were used to evaluate the prognostic significance of TMSB10 in patients with BCa. The data indicated that the mRNA levels of were significantly overexpressed in BCa cell lines. In addition, the protein levels of TMSB10 were overexpressed in BCa tissues compared with those in adjacent normal tissues. In 55/101 (54.5%) BCa specimens, high expression levels of TMSB10 were noted. Statistical analysis revealed that the high expression of TMSB10 was positively associated with muscular invasion (P<0.05). In addition, a high expression of TMSB10 was associated with shorter overall survival (OS) of patients (P<0.05; log-rank test). The univariate and multivariate analyses suggested that the protein overexpression of TMSB10 was an unfavorable prognostic factor for OS (P<0.05) in patients with BCa. Knockdown of the expression of TMSB10 significantly suppressed cell migration and invasion. In conclusion, TMSB10 can be considered an independent factor for the poor prognosis of patients with BCa. The targeting of TMSB10 can reduce the migration and invasion of BCa cells.
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http://dx.doi.org/10.3892/etm.2019.8006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781816PMC
November 2019

Analysis of Volatile Compounds in Pears by HS-SPME-GC×GC-TOFMS.

Molecules 2019 May 9;24(9). Epub 2019 May 9.

School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.

Aroma plays an important role in fruit quality and varies among different fruit cultivars. In this study, a sensitive and accurate method based on headspace solid-phase microextraction (HS-SPME) coupled with comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) was developed to comprehensively compare aroma components of five pear cultivars. In total, 241 volatile compounds were identified and the predominant volatile compounds were esters (101 compounds), followed by alcohols (20 compounds) and aldehydes (28 compounds). The longyuanyangli has the highest relative concentration (838.12 ng/g), while the Packham has the lowest (208.45 ng/g). This study provides a practical method for pear aroma analysis using SPME and GC×GC-TOFMS.
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http://dx.doi.org/10.3390/molecules24091795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539139PMC
May 2019

Vertical distribution of I and radiocesium in forest soil collected near the Fukushima Daiichi Nuclear Power Plant boundary.

Environ Pollut 2019 Jul 13;250:578-585. Epub 2019 Apr 13.

Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki, Aomori, 036-8564, Japan. Electronic address:

Three soil core samples were collected from a forest located about 1.1 km south of the Fukushima Daiichi Nuclear Power Plant (FDNPP) boundary in 2017, and the vertical profiles of I from the FDNPP accident were determined by the combination of TMAH (tetramethyl ammonium hydroxide) extraction and ICP-MS/MS analysis. The humus layer above the soil layer was heavily contaminated with Cs (1983-5985 Bq g) and Cs (1947-5902 Bq g) (decay-corrected to March 11, 2011). The I activity concentrations decreased sharply with the soil depth, from 1894 to 34.1, from 9384 to 78.9, and from 2536 to 51.3 mBq kg, for the three sites. Downward migration of I was slightly faster than the one of Cs. In addition, the cumulative I inventories were observed to be 43.4 ± 1.0, 71.7 ± 1.8, and 56.5 ± 1.8 Bq m, respectively. Subsequently, the cumulative I inventories were estimated to be 1.76 ± 0.06, 2.90 ± 0.11, and 2.28 ± 0.10 GBq m (decay-corrected to March 11, 2011), respectively. Finally, the total atmospheric deposition of I on the land of Japan due to the FDNPP accident was estimated to be around 1.09-1.71 kg (7.11-11.2 GBq).
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http://dx.doi.org/10.1016/j.envpol.2019.04.053DOI Listing
July 2019

U and radiocesium in river bank soil and river sediment in Fukushima Prefecture, after the Fukushima Daiichi Nuclear Power Plant accident.

Chemosphere 2019 Jun 12;225:388-394. Epub 2019 Mar 12.

Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki, Aomori, 036-8564, Japan. Electronic address:

Almost 8 years after the Japanese Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, data for U and U/U have mainly remained limited to only a few heavily contaminated samples. In the present study, activities of U, Cs, and Cs, along with U, U, U, in 15 river bank soil and 10 river sediment samples, were measured by ICP-MS/MS and γ spectrometry. The Cs activities and Cs/Cs activity ratios (decay-corrected to March 11, 2011) in these 15 river bank soil samples were from 74.8 to 3.88 × 10 Bq kg and from 0.944 to 1.02, respectively; and in these 10 river sediment samples were from 87.1 to 1.86 × 10 Bq kg and from 0.904 to 0.990, respectively. The U activities and U/U atom ratios in these soil samples were in the respective ranges of (0.139-17.6) × 10 Bq kg and (0.259-3.83) × 10; and in these sediment samples were in the respective ranges of (0.884-27.0) × 10 Bq kg and (1.12-5.04) × 10. For one river sediment core sample, Cs and U activities decreased with the depth indicating Cs and U accumulated in the river sediment with time. Unlike Cs, no clear evidence of FDNPP accident-derived U has been found in this study, although further monitoring is encouraged to establish the background database on U/U for its potential application as a tracer in environmental studies.
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http://dx.doi.org/10.1016/j.chemosphere.2019.03.061DOI Listing
June 2019

Glycine increases glyoxalase-1 function by promoting nuclear factor erythroid 2-related factor 2 translocation into the nucleus of kidney cells of streptozotocin-induced diabetic rats.

J Diabetes Investig 2019 Sep 28;10(5):1189-1198. Epub 2019 Mar 28.

Endocrinology, Peking University First Hospital, Beijing, China.

Aims/introduction: We have previously reported that glycine suppresses the advanced glycation end-products signaling pathway and mitigates subsequent oxidative stress in the kidneys of diabetic rats. In the present study, we investigated whether this beneficial effect was associated with upregulation of glyoxalase-1 (Glo1) and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2).

Materials And Methods: Both healthy rats and streptozotocin-induced diabetic rats were administrated with glycine (1% added to the drinking water) for 12 weeks. The function of Glo1, messenger ribonucleic acid (mRNA) and protein expressions of Nrf2, and markers of oxidative status were measured in the kidneys. The mRNA expressions of other downstream signaling molecules of the Nrf2 pathway were also determined.

Results: The mRNA and protein expressions, as well as the activity of Glo1, were decreased in the kidneys of diabetic rats, accompanied by diminished glutathione levels. After glycine treatment, these parameters of Glo1 function were markedly increased. Compared with the control group, the levels of Nrf2 mRNA and protein in the total kidney lysis were both markedly elevated in the diabetic group and glycine-treated group. However, the nuclear translocation of Nrf2 was significantly increased in the glycine-treated group than in the diabetic group. In addition, the anti-oxidant capacity and the expressions of other downstream molecules of the Nrf2 signaling pathway were significantly increased after glycine treatment.

Conclusions: The present study shows that glycine might enhance the function of Glo1 and restore anti-oxidant defense by promoting the nuclear translocation of Nrf2, thus inhibiting advanced glycation end-products formation and protecting against renal oxidative stress.
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http://dx.doi.org/10.1111/jdi.13032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717822PMC
September 2019

Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells.

BMC Cancer 2019 Jan 8;19(1):27. Epub 2019 Jan 8.

Department of Urology, Southern Medical University Third Medical College, Guangzhou, 510317, China.

Background: Docetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application.

Objective: To understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance.

Methods: We established Doc resistant cell lines and explored the role of Ezh2 in the development of Doc resistance by overexpressing its cDNA or using its inhibitor.

Results: We found that Ezh2 was induced in our established Doc resistant (DocR) cells, which was attributable to the silenced expression of miR-101-3p and miR-138-5p. Blockage of Ezh2 activity by either inhibitor or miRNA mimics could overcome Doc resistance by suppressing Doc-induced cancer stem cells populations. Mechanistically, Ezh2 activity was required for the induced expression of Nanog, Sox2 and CD44 upon Doc treatment.

Conclusions: Targeting Ezh2 could overcome Doc resistance.
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http://dx.doi.org/10.1186/s12885-018-5228-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324167PMC
January 2019

First report on global fallout U and uranium atom ratios in soils from Hunan Province, China.

J Environ Radioact 2019 Feb 18;197:1-8. Epub 2018 Nov 18.

Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

More nuclear power plants continue to be built in China. Due to its long half-life, radiotoxicity and potential application as an environmental tracer, U is one of the most important artificial radionuclides deserving more study since activity data are important for risk assessment. However, the ultra-trace activity of U and its dilution by natural uranium isotopes make it difficult to distinguish its sources and there are only limited global fallout U data for present in Chinese environmental samples. In order to understand the background levels for uranium isotopes, especially U, and clarify their sources, inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) was applied to analyze uranium isotopes in 48 soil samples from Hunan Province, China. The U, U, U and U concentrations were measured as 9.91-33.7, 0.312-1.43, 6.63-28.7 Bq kg and (1.61-21.3) × 10 atoms g, while, the U/U, U/U and U/U atom ratios were (0.470-4.91) × 10, (5.10-9.31) × 10, and (7.11-7.82) × 10, respectively. The uranium isotopic fractionation may be due to irrigation of the agricultural lands where the samples were collected. Considering the facts that neither previous nuclear tests nor nuclear accidents had occurred in Hunan Province and the present U/U atom ratios were included in the range of global fallout values in other areas, it may be concluded that U in soils from Hunan Province is mainly from global fallout. To the best of the authors' knowledge, the presence of global fallout U in soil samples from China has been confirmed for the first time, and these values may be useful as background data for risk assessment in the future.
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http://dx.doi.org/10.1016/j.jenvrad.2018.11.009DOI Listing
February 2019

Application of synchrotron radiation and other techniques in analysis of radioactive microparticles emitted from the Fukushima Daiichi Nuclear Power Plant accident-A review.

J Environ Radioact 2019 Jan 25;196:29-39. Epub 2018 Oct 25.

Institute of Radiation Emergency Medicine, Hirosaki University, 66-1 Hon-cho, Hirosaki, Aomori, 036-8564, Japan. Electronic address:

During the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, large amounts of radioactive materials were released into the environment. Among them, a large proportion of the radionuclides, such as Cs, entered into the environment as radioactive microparticles (RMs). In recent years, the characterization of RMs based on synchrotron radiation (SR) techniques has been reported, since their physical and chemical properties played an important role in evaluating the chemical reactions and physical changes that occurred when the nuclear material meltdowns took place. In this review, we summarize separation and measurement technologies used in studies of RMs, and we emphasize the application of SR-based techniques in the characterization of RMs. We report research progress, including information for elemental composition, isotopic distribution, radioactivity, and formation processes. Also, we compare the RMs from the FDNPP and the Chernobyl Nuclear Power Plant accidents. The SR-based technologies offer great improvement in the resolution and precision compared to conventional technologies, such as X-ray fluorescence and X-ray diffraction.
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http://dx.doi.org/10.1016/j.jenvrad.2018.10.013DOI Listing
January 2019

Organic Sensitizers with Extended Conjugation Frameworks as Cosensitizers of Porphyrins for Developing Efficient Dye-Sensitized Solar Cells.

ACS Appl Mater Interfaces 2018 Nov 2;10(45):38880-38891. Epub 2018 Nov 2.

College of Chemical and Environmental Engineering , Shandong University of Science and Technology , Qingdao 266510 , P. R. China.

Relatively high efficiencies have been achieved for porphyrin-based dye-sensitized solar cells. For the purpose of designing efficient cosensitizers, we herein report systematically optimized dyes XC1-XC5 employing a triphenylamine donor, a benzothiadiazole moiety as the auxiliary acceptor, and a benzoic acid acceptor. One hexyl and four hexyloxy groups were introduced, and an ethynylene moiety was introduced between the donor and the auxiliary acceptor to afford XC1. To further extend the absorption wavelength, a second ethynylene moiety was introduced between the acceptor and the auxiliary acceptor to afford XC2. XC3 and XC4 were designed by introducing one and two methyl substituents, respectively, into the meta-positions of the anchoring carboxyl group. XC5 was further synthesized by inserting a cyano substituent into one of the ortho-positions of the carboxyl group with the purpose to strengthen the intramolecular charge-transfer effect and thus broaden the absorption wavelength. As expected, compared with the J (14.29 mA·cm) of XC1, the corresponding J values for XC2-XC5 were enhanced to 16.50, 16.95, 16.73, and 17.74 mA·cm, respectively. Moreover, XC4 exhibits the highest V of 770 mV owing to the presence of a maximum of seven chains, which can effectively suppress dye aggregation. As a result, compared with XC1, XC2-XC5 exhibit improved efficiencies of 8.67, 9.05, 8.78, and 9.30%, respectively. In addition, the efficiencies of XC3 and XC5 were further enhanced by cosensitizing them with our previously reported porphyrin dye XW28 under various conditions. Finally, a remarkable efficiency of 10.50% was achieved for the cells cosensitized with XC5 and XW28. These results indicate that the combination of good planarity of the extended D-π-A framework with multiple alkoxy/alkyl chains may compose an effective optimizing strategy for designing and synthesizing excellent cosensitizers for porphyrins.
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http://dx.doi.org/10.1021/acsami.8b12883DOI Listing
November 2018

Characterization of rabbit urine-derived stem cells for potential application in lower urinary tract tissue regeneration.

Cell Tissue Res 2018 Nov 31;374(2):303-315. Epub 2018 Jul 31.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Tissue-engineered urethra with autologous cells seeded on biodegradable scaffolds offers an alternative for lower urinary tract reconstruction. Rabbit is most commonly used as an animal model in urethra and bladder tissue repair. The goal of this study is to characterize rabbit urine-derived stem cells (rUSC) and induce these cells to differentiate into urothelial and smooth muscle cells as an autologous cell source for potential use in lower urinary tract tissue regeneration in a rabbit model. We successfully cultured rUSC from 12 urine samples and 13 bladder wash samples of six rabbits. rUSC colonies appeared more in the bladder wash solution (2-4/15 ml) than those in the urine samples (1-2 clones/15 ml urine). The cells displayed rice grain-like in morphology. Mean population doubling of rUSC was 48.5 ± 6.2 and average doubling time was 25.7 ± 8.4 h, indicating that a single of rUSC clone generated about 4 × 10 cells in 50 days. The rUSC were positive for CD29, CD90 and CD105 but negative for CD31, CD34 and CD45 in flow cytometry. When exposed to PDGF-BB and TGF-β1, these cells could differentiate into spindle-like cells, expressing smooth muscle-specific proteins, including α-smooth muscle action, desmin and myosin. Urothelially differentiated rUSC expressed urothelial-specific proteins, i.e., AE1/AE3 and E-cadherin when exposed to epidermal growth factor (EGF). Osteogenic-differentiated rUSC expressed osteogenic marker, i.e., alkaline phosphatase when exposed to serum containing DMEM low-glucose medium with osteogenic supplements. In conclusion, rUSC can be isolated from bladder wash or urine samples and cultured in vitro. There stem cells possess strong proliferative ability and are capable of differentiating in urothelial, myogenic and osteogenic lineages. Thus, rUSC are a potential alternative autologous cell source for lower urinary tract repair with tissue engineering technology in a rabbit model.
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http://dx.doi.org/10.1007/s00441-018-2885-zDOI Listing
November 2018

A review of measurement methodologies and their applications to environmental Sr.

J Environ Radioact 2018 Dec 18;192:321-333. Epub 2018 Jul 18.

Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

The high fission yield product Sr has been released into the environment in large amounts due to nuclear weapon tests, nuclear power plant accidents, and nuclear fuel reprocessing industries. It is a long half-life radionuclide (28.9 y), with serious consequences to human health; hence, it is desirable to perform routine monitoring of Sr in environmental samples. Many Sr radiometric methods have been developed in the past decades, which generally require complicated separation and purification steps with a relatively long analytical time. Moreover, some nominally rapid methods usually have high method detection limits, making them unsuitable for the environmental samples with ultra-low Sr levels. In this review, some rapid and practical methods for Sr routine monitoring are summarized. Different sample pretreatments and major purification procedures for Sr developed in recent years, such as variable digestion methods and extraction chromatography using Sr resin or DGA resin, are especially described. Additionally, four conventional and widely used β spectrometric and mass spectrometric methods are demonstrated. Finally, Sr evaluations focusing on contaminated soil and seawater samples collected after the Fukushima Daiichi Nuclear Power Plant accident, and Sr application as tracers for environmental behavior are also reviewed.
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http://dx.doi.org/10.1016/j.jenvrad.2018.07.013DOI Listing
December 2018

TR4 nuclear receptor promotes clear cell renal cell carcinoma (ccRCC) vasculogenic mimicry (VM) formation and metastasis via altering the miR490-3p/vimentin signals.

Oncogene 2018 11 4;37(44):5901-5912. Epub 2018 Jul 4.

George Whipple Lab for Cancer Research, Departments of Urology and Pathology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.

While TR4 nuclear receptor plays key roles to promote prostate cancer progression, its roles to alter the progression of clear cell renal cell carcinoma (ccRCC), remains unclear. Here, we demonstrate that TR4 can promote the ccRCC cell vasculogenic mimicry (VM) formation and its associated metastasis via modulating the miR490-3p/vimentin (VIM) signals. Mechanism dissection revealed that TR4 might increase the oncogene VIM expression via decreasing the miR-490-3p expression through direct binding to the TR4-response-elements (TR4REs) on the promoter region of miR-490-3p, which might then directly target the 3' UTR of VIM-mRNA to increase its protein expression. Preclinical studies using the in vivo mouse model with xenografted RCC Caki-1 cells into the sub-renal capsule of nude mice also found that TR4 could promote the ccRCC VM and its associated metastasis via modulating the miR490-3p/VIM signals. Together, results from preclinical studies using multiple RCC cell lines and the in vivo mouse model all conclude that TR4 may play a key role to promote ccRCC VM formation and metastasis and targeting the newly identified TR4/miR-490-3p/VIM signals with small molecules may help us to develop a new therapeutic approach to better suppress the ccRCC metastasis.
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http://dx.doi.org/10.1038/s41388-018-0269-1DOI Listing
November 2018

Simultaneous determination of free and total choline and l-carnitine in infant formula using hydrophilic interaction liquid chromatography with tandem mass spectrometry.

J Sep Sci 2018 Aug 17;41(16):3176-3185. Epub 2018 Jul 17.

Shandong Institute for Food and Drug Control, Jinan, China.

A quick, simple, and reliable method was developed for the simultaneous determination of free and total choline and l-carnitine in infant formula employing a novel hydrophilic interaction liquid chromatography with tandem mass spectrometry method. Microwave-assisted hydrolysis was used to shorten the hydrolysis time to only 15 min. A novel Click XIon zwitterionic stationary phase was chosen because it gave better retention, perfect resolution, and sharper symmetrical peaks compared to traditional columns. The matrix effect under different experimental conditions was evaluated by using the matrix effect factor, which employs stable isotopically labeled internal standards and is more appropriate for evaluating the matrix effect related to endogenous analytes. The accuracy and precision of the method were validated with certified reference materials. The fortified recovery values for choline and l-carnitine were between 85.0 and 104% with relevant standard deviations <5.0%. The established method was applied to the analysis of real infant formulas, demonstrating its applicability and feasibility.
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http://dx.doi.org/10.1002/jssc.201800483DOI Listing
August 2018

The Increased Endogenous Sulfur Dioxide Acts as a Compensatory Mechanism for the Downregulated Endogenous Hydrogen Sulfide Pathway in the Endothelial Cell Inflammation.

Front Immunol 2018 30;9:882. Epub 2018 Apr 30.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Endogenous hydrogen sulfide (HS) and sulfur dioxide (SO) are regarded as important regulators to control endothelial cell function and protect endothelial cell against various injuries. In our present study, we aimed to investigate the effect of endogenous HS on the SO generation in the endothelial cells and explore its significance in the endothelial inflammation and . The human umbilical vein endothelial cell (HUVEC) line (EA.hy926), primary HUVECs, primary rat pulmonary artery endothelial cells (RPAECs), and purified aspartate aminotransferase (AAT) protein from pig heart were used for experiments. A rat model of monocrotaline (MCT)-induced pulmonary vascular inflammation was used for experiments. We found that endogenous HS deficiency caused by cystathionine-γ-lyase (CSE) knockdown increased endogenous SO level in endothelial cells and enhanced the enzymatic activity of AAT, a major SO synthesis enzyme, without affecting the expressions of AAT1 and AAT2. While HS donor could reverse the CSE knockdown-induced increase in the endogenous SO level and AAT activity. Moreover, HS donor directly inhibited the activity of purified AAT protein, which was reversed by a thiol reductant DTT. Mechanistically, HS donor sulfhydrated the purified AAT1/2 protein and rescued the decrease in the sulfhydration of AAT1/2 protein in the CSE knockdown endothelial cells. Furthermore, an AAT inhibitor l-aspartate-β-hydroxamate (HDX), which blocked the upregulation of endogenous SO/AAT generation induced by CSE knockdown, aggravated CSE knockdown-activated nuclear factor-κB pathway in the endothelial cells and its downstream inflammatory factors including ICAM-1, TNF-α, and IL-6. In experiment, HS donor restored the deficiency of endogenous HS production induced by MCT, and reversed the upregulation of endogenous SO/AAT pathway sulfhydrating AAT1 and AAT2. In accordance with the results of the experiment, HDX exacerbated the pulmonary vascular inflammation induced by the broken endogenous HS production in MCT-treated rat. In conclusion, for the first time, the present study showed that HS inhibited endogenous SO generation by inactivating AAT the sulfhydration of AAT1/2; and the increased endogenous SO generation might play a compensatory role when HS/CSE pathway was downregulated, thereby exerting protective effects in endothelial inflammatory responses and .
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http://dx.doi.org/10.3389/fimmu.2018.00882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936987PMC
June 2019
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