Publications by authors named "Zhigang Zhu"

61 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

Antibiotic Conditioning and Single Gavage Allows Stable Engraftment of Human Microbiota in Mice.

Methods Mol Biol 2021 ;2327:281-291

Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.

Mice transplanted with human microbiota are essential tools for studying the role of microbiota in health and disease, striving for the development of microbiota-modulating therapeutics. Traditionally, germ-free mice have been the principal option for establishing human microbiota-associated (HMA) mouse models, leading to significant insights into the composition and function of the human microbiota. However, there are limitations in using germ-free mice as recipients of human microbiota, including considerable resource allocation to establish and maintain the model and incomplete development of their immune system and physiological functions. Thus, antibiotic-treated, non-germ-free mice have been developed as an alternative to satisfy the growing demand for an accessible HMA mouse model. Several methods have been described for creating "humanized" mice. These protocols vary in their key components, mainly antibiotic conditioning and frequency of oral gavage. To address this practical challenge and formulate a simple and repeatable protocol, we established a HMA mouse model with antibiotic-treated conventional and specific-pathogen free (SPF) C57BL/6J mice, revealing that a single oral gavage allows stable engraftment of the human microbiota. In this chapter, we present our simple protocol for antibiotic conditioning to prepare mice for stable engraftment of human gut microbiota.
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http://dx.doi.org/10.1007/978-1-0716-1518-8_17DOI Listing
January 2021

Stability Assessment of the Rumen Bacterial and Archaeal Communities in Dairy Cows Within a Single Lactation and Its Association With Host Phenotype.

Front Microbiol 2021 6;12:636223. Epub 2021 Apr 6.

Department of Animal Science, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark.

Better characterization of changes in the rumen microbiota in dairy cows over the lactation period is crucial for understanding how microbial factors may potentially be interacting with host phenotypes. In the present study, we characterized the rumen bacterial and archaeal community composition of 60 lactating Holstein dairy cows (33 multiparous and 27 primiparous), sampled twice within the same lactation with a 122 days interval. Firmicutes and Bacteroidetes dominated the rumen bacterial community and showed no difference in relative abundance between samplings. Two less abundant bacterial phyla (SR1 and Proteobacteria) and an archaeal order (Methanosarcinales), on the other hand, decreased significantly from the mid-lactation to the late-lactation period. Moreover, between-sampling stability assessment of individual operational taxonomic units (OTUs), evaluated by concordance correlation coefficient (C-value) analysis, revealed the majority of the bacterial OTUs (6,187 out of 6,363) and all the 79 archaeal OTUs to be unstable over the investigated lactation period. The remaining 176 stable bacterial OTUs were mainly assigned to , unclassified Prevotellaceae, and unclassified Bacteroidales. Milk phenotype-based screening analysis detected 32 bacterial OTUs, mainly assigned to unclassified Bacteroidetes and Lachnospiraceae, associated with milk fat percentage, and 6 OTUs, assigned to and unclassified Ruminococcaceae, associated with milk protein percentage. These OTUs were only observed in the multiparous cows. None of the archaeal OTUs was observed to be associated with the investigated phenotypic parameters, including methane production. Co-occurrence analysis of the rumen bacterial and archaeal communities revealed to be positively correlated with the archaeal genus (Pearson = 0.76) and unclassified Methanomassiliicoccaceae (Pearson = 0.64); , on the other hand, was negatively correlated with (Pearson = -0.56). In conclusion, the rumen bacterial and archaeal communities of dairy cows displayed distinct stability at different taxonomic levels. Moreover, specific members of the rumen bacterial community were observed to be associated with milk phenotype parameters, however, only in multiparous cows, indicating that dairy cow parity could be one of the driving factors for host-microbe interactions.
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http://dx.doi.org/10.3389/fmicb.2021.636223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076905PMC
April 2021

High levels of Tim-3Foxp3Treg cells in the tumor microenvironment is a prognostic indicator of poor survival of diffuse large B cell lymphoma patients.

Int Immunopharmacol 2021 Jul 14;96:107662. Epub 2021 Apr 14.

Department of Geriatrics, Gastroenterology Ward, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, China. Electronic address:

Foxp3Treg cells display phenotypic and functional heterogeneity, which express high levels of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) in the tumor microenvironment (TME) of colorectal and lung cancer. High abundance of Tim-3Foxp3Treg (TFT) cells are associated with poor prognosis in these patients. However, the expression patterns and roles of TFT cells in TME of diffuse large B cell lymphoma (DLBCL) remain to be established. Double immunofluorescence and flow cytometry analyses were employed to investigate TFT cell enrichment in paraffin-embedded fresh tumor tissues from patients with DLBCL. Spearman's or Pearson's correlation and Kaplan-Meier survival analyses were further applied to decide the prognostic value of TFT cell levels in DLBCL. The IL-10-secreting function of TFT cells in vitro was examined via flow cytometry and ELISA. Our results showed for the first time that TFT cells are highly enriched in TME of DLBCL patients and associated with predictions of poor prognoses. TFT cell-induced secretion of IL-10 in the TME was suppressed by an anti-Tim-3 antibody in vitro. In conclusion, high abundance of TFT cells in the TME is predictive of poor outcomes of DLBCL. TFT cells promote DLBCL development partly by secreting IL-10 in the TME. Anti-Tim-3 antibodies (that block IL-10 secretion) may present an effective therapeutic agent for DLBCL.
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http://dx.doi.org/10.1016/j.intimp.2021.107662DOI Listing
July 2021

Automatic Modulation Classification Based on Deep Feature Fusion for High Noise Level and Large Dynamic Input.

Sensors (Basel) 2021 Mar 17;21(6). Epub 2021 Mar 17.

School of Electronic Engineering, Xidian University, Xi'an 710071, China.

Automatic modulation classification (AMC) is playing an increasingly important role in spectrum monitoring and cognitive radio. As communication and electronic technologies develop, the electromagnetic environment becomes increasingly complex. The high background noise level and large dynamic input have become the key problems for AMC. This paper proposes a feature fusion scheme based on deep learning, which attempts to fuse features from different domains of the input signal to obtain a more stable and efficient representation of the signal modulation types. We consider the complementarity among features that can be used to suppress the influence of the background noise interference and large dynamic range of the received (intercepted) signals. Specifically, the time-series signals are transformed into the frequency domain by Fast Fourier transform (FFT) and Welch power spectrum analysis, followed by the convolutional neural network (CNN) and stacked auto-encoder (SAE), respectively, for detailed and stable frequency-domain feature representations. Considering the complementary information in the time domain, the instantaneous amplitude (phase) statistics and higher-order cumulants (HOC) are extracted as the statistical features for fusion. Based on the fused features, a probabilistic neural network (PNN) is designed for automatic modulation classification. The simulation results demonstrate the superior performance of the proposed method. It is worth noting that the classification accuracy can reach 99.8% in the case when signal-to-noise ratio (SNR) is 0 dB.
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http://dx.doi.org/10.3390/s21062117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003108PMC
March 2021

Flexible fabric gas sensors based on reduced graphene-polyaniline nanocomposite for highly sensitive NHdetection at room temperature.

Nanotechnology 2021 May 3;32(30). Epub 2021 May 3.

School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, 201209, People's Republic of China.

A flexible fabric gas sensor for the detection of sub-ppm-level NHis reported in this paper. The reduced graphene oxide (rGO)-polyaniline (PANI) nanocomposite was successfully coated on cotton thread via anpolymerization technique. The morphology, microstructure and composition were analyzed by field-emission scanning electron microscope, x-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy. Furthermore, we have studied the responses of the rGO-PANI nanocomposite-based flexible sensors for the detection of NHvarying from 1-100 ppm, operated at 22 °C. At the optimized concentration of rGO, the response of these sensors increased by 4-5 times in comparison with the pristine rGO and PANI. These flexible sensors exhibited fast response, remarkable long-term stability, good selectivity and a low detection limit. The sensing mechanism for the high sensing performance has been thoroughly discussed and it is mainly due to the distinctive 1D fiber structure, the formation of a p-p heterojunction between the rGO nanosheets and PANI. The rGO-PANI composite-based fabric sensor with low power consumption is a potential flexible electronic device for the detection of NH.
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http://dx.doi.org/10.1088/1361-6528/abf455DOI Listing
May 2021

Donor Microbiota Composition and Housing Affect Recapitulation of Obese Phenotypes in a Human Microbiota-Associated Murine Model.

Front Cell Infect Microbiol 2021 22;11:614218. Epub 2021 Feb 22.

Division of Basic & Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, United States.

Human microbiota-associated (HMA) mouse models offer a valuable approach to study the role of intestinal microbiota in the development of obesity. In this study, we used an HMA model to evaluate whether engraftment of human obese or lean microbiota, from each of three donors, could recapitulate host phenotypes under conventional and specific-pathogen-free housing. Microbiota engraftment was correlated with donor relative abundances of the class Bacteroidia (Spearman's = 0.73, ≤ 0.001), and one obese donor resulted in significant weight gain ( ≤ 0.003) and compromised insulin sensitivity under conventional housing. SPF housing partially blunted phenotypic response. Results of this study indicate that our HMA model partially recapitulates obese phenotypes under conventional housing and highlights a need to consider donor-specific effects as well as housing conditions when studying the role of the microbiota in obesity.
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http://dx.doi.org/10.3389/fcimb.2021.614218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937608PMC
June 2021

Endogenous SO-dependent Smad3 redox modification controls vascular remodeling.

Redox Biol 2021 05 18;41:101898. Epub 2021 Feb 18.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China; Key Laboratory of Cardiovascular Sciences, Ministry of Education, China. Electronic address:

Sulfur dioxide (SO) has emerged as a physiological relevant signaling molecule that plays a prominent role in regulating vascular functions. However, molecular mechanisms whereby SO influences its upper-stream targets have been elusive. Here we show that SO may mediate conversion of hydrogen peroxide (HO) to a more potent oxidant, peroxymonosulfite, providing a pathway for activation of HO to convert the thiol group of protein cysteine residues to a sulfenic acid group, aka cysteine sulfenylation. By using site-centric chemoproteomics, we quantified >1000 sulfenylation events in vascular smooth muscle cells in response to exogenous SO. Notably, ~42% of these sulfenylated cysteines are dynamically regulated by SO, among which is cysteine-64 of Smad3 (Mothers against decapentaplegic homolog 3), a key transcriptional modulator of transforming growth factor β signaling. Sulfenylation of Smad3 at cysteine-64 inhibits its DNA binding activity, while mutation of this site attenuates the protective effects of SO on angiotensin II-induced vascular remodeling and hypertension. Taken together, our findings highlight the important role of SO in vascular pathophysiology through a redox-dependent mechanism.
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http://dx.doi.org/10.1016/j.redox.2021.101898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933484PMC
May 2021

Vincristine upregulates PD-L1 and increases the efficacy of PD-L1 blockade therapy in diffuse large B-cell lymphoma.

J Cancer Res Clin Oncol 2021 Mar 2;147(3):691-701. Epub 2021 Jan 2.

Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, People's Republic of China.

Background: Some chemotherapy drugs have immunomodulatory effects on specific tumors. The potential of vincristine (VCR) in the R-CHOP regimen to act as both a chemotherapeutic and an immunomodulatory agent via PD-L1 in tumor cells remains unclear.

Methods: In vitro screening VCR showed that the IC50 value of VCR in the DLBCL cell lines was approximately 2 nM. Western blotting and q-PCR were used to detect the expression of PD-L1. The effect of VCR combined with PD-L1 mAb was tested in a co-culture system of LY-OCI-3 cells and peripheral blood mononuclear cells and in DLBCL xenograft mouse model. Flow cytometry was used to determine the proportion of T lymphocyte subsets. The effect of the STAT3 inhibitor nifuroxazide on VCR-induced PD-L1 expression was tested in LY-OCI-3 and SU-DHL-4 cells.

Results: VCR upregulated PD-L1 protein and mRNA expression in various DLBCL cell lines. PD-L1 Ab combined with VCR significantly increased the proportion of CD8 + Granzyme B + , INF-γ + or TNF-α + CD3 + T cells. VCR + PD-L1 Ab inhibited tumor growth more effectively than VCR monotherapy, whereas PD-L1 Ab alone had no significant effect. Survival time did not differ significantly between the PD-L1 Ab group and the control group, whereas it was significantly longer in the VCR monotherapy and combination groups which showed more longer survival compared with the former. Nifuroxazide downregulated p-STAT3 and PD-L1 protein levels.

Conclusions: VCR upregulated PD-L1 expression in DLBCL cells partially by promoting the p-STAT3; VCR combined with PD-L1 Ab activated effector T cells and increased the antitumor immune response in vitro and in vivo.
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http://dx.doi.org/10.1007/s00432-020-03446-wDOI Listing
March 2021

Comparative decay of culturable faecal indicator bacteria, microbial source tracking marker genes, and enteric pathogens in laboratory microcosms that mimic a sub-tropical environment.

Sci Total Environ 2021 Jan 9;751:141475. Epub 2020 Aug 9.

Department of Soil, Water, and Climate, and the BioTechnology Institute, University of Minnesota, St. Paul, MN 55108, USA.

Enteric pathogens can be present in drinking water catchments due to several point and non-point sources of faecal contamination. Pathogen and contaminant signatures will decay due to environmental stresses, such as temperature, Ultra Violet (UV) radiation, salinity, and predation. In this study, we determined the decay of the culturable faecal indicator bacterium (FIB) Escherichia coli (E. coli), two sewage-associated marker genes (Bacteroides HF183 and crAssphage CPQ_056), and enteric pathogens (Campylobacter spp., human adenovirus 40/41, and Cryptosporidium parvum) in two freshwater laboratory microcosms using culture-based, quantitative PCR (qPCR) and vital dye (determine the fraction of viable Cryptosporidium oocysts) assays. Freshwater samples from the Lake Wappa and Lake Wivenhoe (Australia) were seeded with untreated sewage and C. parvum oocysts, and their declining concentrations were measured over a 28-day period. Moreover, 16S rRNA amplicon sequencing was also undertaken to determine the change/shift in sewage-associated bacterial communities using SourceTracker. Overall, culturable E. coli and the HF183 marker gene decayed significantly (p < 0.05) faster than did the qPCR measured enteric pathogens suggesting that the absence of culturable FIB or qPCR HF183 in water samples may not indicate the absence of pathogens. The decay of crAssphage was similar to that of HAdV 40/41 and other pathogens tested, suggesting crAssphage may be a better surrogate for enteric viruses in sub-tropical catchment waters. The decay rates were greater at 25 °C compared to 15 °C, suggesting that FIB and pathogens persist longer in the winter season compared to summer. Overall decay rates of the tested microorganisms in this microcosm study suggest that sub-tropical conditions, especially temperature, have a negative impact on the persistence of tested microorganisms. Sewage-associated bacterial communities also showed similar patterns. Based on the results, which showed differences in simulated summer and winter temperatures for pathogen decay, corresponding management options and treatment need to be adjusted accordingly to minimize human health risks effectively.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141475DOI Listing
January 2021

ASSIST: Evaluating the usability and performance of an indoor navigation assistant for blind and visually impaired people.

Assist Technol 2020 Sep 2:1-11. Epub 2020 Sep 2.

Department of Computer Science, The City College of New York, New York, USA.

This paper describes the interface and testing of an indoor navigation app - ASSIST - that guides blind & visually impaired (BVI) individuals through an indoor environment with high accuracy while augmenting their understanding of the surrounding environment. ASSIST features personalized interfaces by considering the unique experiences that BVI individuals have in indoor wayfinding and offers multiple levels of multimodal feedback. After an overview of the technical approach and implementation of the first prototype of the ASSIST system, the results of two pilot studies performed with BVI individuals are presented - a performance study to collect data on mobility (walking speed, collisions, and navigation errors) while using the app, and a usability study to collect user evaluation data on the perceived helpfulness, safety, ease-of-use, and overall experience while using the app. Our studies show that ASSIST is useful in providing users with navigational guidance, improving their efficiency and (more significantly) their safety and accuracy in wayfinding indoors. Findings and user feedback from the studies confirm some of the previous results, while also providing some new insights into the creation of such an app, including the use of customized user interfaces and expanding the types of information provided.
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http://dx.doi.org/10.1080/10400435.2020.1809553DOI Listing
September 2020

Scale-up Design of a Fluorescent Fluid Photochemical Microreactor by 3D Printing.

ACS Omega 2020 Apr 27;5(13):7666-7674. Epub 2020 Mar 27.

Department of Chemistry, Dalian University of Technology, Dalian 116024, P. R. China.

The integration of light-converting media and microflow chemistry renders new opportunities for high-efficient utilization of solar energy to drive chemical reactions. Recently, we proposed a design of fluorescent fluid photochemical microreactor (FFPM) with a separate light channel and reaction channel, which displays excellent advantages in energy efficiency, flexibility, and general use. However, the limitations of the scalability of the microchannel reactor are still a big challenge to be overcome. Herein, we illustrate the scalability of such an FFPM via a 2 numbering-up strategy by 3D printing technology. Channel shape, number, and interchannel spacing have been optimized, and the serpentine FFPM shows the best scalability with an excellent conversion rate and massive throughput. Reactors with up to eight channels have been fabricated and displayed conversions comparable to that obtained in a single-channel reactor, which provides a feasible strategy and an optimized structure model for batch production of fine chemicals.
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http://dx.doi.org/10.1021/acsomega.0c00511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144148PMC
April 2020

Predictive ability of host genetics and rumen microbiome for subclinical ketosis.

J Dairy Sci 2020 May 18;103(5):4557-4569. Epub 2020 Mar 18.

Center for Quantitative Genetics and Genomics, Aarhus University, DK-8830 Tjele, Denmark.

Subclinical metabolic disorders such as ketosis cause substantial economic losses for dairy farmers in addition to the serious welfare issues they pose for dairy cows. Major hurdles in genetic improvement against metabolic disorders such as ketosis include difficulties in large-scale phenotype recording and low heritability of traits. Milk concentrations of ketone bodies, such as acetone and β-hydroxybutyric acid (BHB), might be useful indicators to select cows for low susceptibility to ketosis. However, heritability estimates reported for milk BHB and acetone in several dairy cattle breeds were low. The rumen microbial community has been reported to play a significant role in host energy homeostasis and metabolic and physiologic adaptations. The current study aims at investigating the effects of cows' genome and rumen microbial composition on concentrations of acetone and BHB in milk, and identifying specific rumen microbial taxa associated with variation in milk acetone and BHB concentrations. We determined the concentrations of acetone and BHB in milk using nuclear magnetic resonance spectroscopy on morning milk samples collected from 277 Danish Holstein cows. Imputed high-density genotype data were available for these cows. Using genomic and microbial prediction models with a 10-fold resampling strategy, we found that rumen microbial composition explains a larger proportion of the variation in milk concentrations of acetone and BHB than do host genetics. Moreover, we identified associations between milk acetone and BHB with some specific bacterial and archaeal operational taxonomic units previously reported to have low to moderate heritability, presenting an opportunity for genetic improvement. However, higher covariation between specific microbial taxa and milk acetone and BHB concentrations might not necessarily indicate a causal relationship; therefore further validation is needed before considering implementation in selection programs.
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http://dx.doi.org/10.3168/jds.2019-17824DOI Listing
May 2020

Preparing copper catalyst by ultrasound-assisted chemical precipitation method.

Ultrason Sonochem 2020 Jun 7;64:105013. Epub 2020 Feb 7.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02135, USA.

In this paper, preparing copper catalyst by ultrasound-assisted chemical precipitation method is investigated. The used equipment is JP-020 ultrasonic cleaner, power and frequency are 180 W and 40 kHz respectively. Under the action of ultrasound, CuSO·5HO is reduced by ascorbic acid to obtain copper. The products are characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and catalytic performance test. The results show that the morphology of copper products is rod-like and irregular granular. Copper catalyst has good catalytic oxidation performance for dyes methylene blue, crystal violet, alizarin red and Rhodamine B. The catalytic efficiency of 10 mg catalyst copper to 6 mg/L methylene blue reaches 98.1%, and the catalytic efficiency of the catalyst increases with the increase of catalyst dosage and the decrease of dye solution concentration. In addition, the new preparation techniques for Cu-based catalysts based on coprecipitation method are compared. Finally, the development trend of the new technology of copper-based catalyst preparation based on coprecipitation method is pointed out.
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http://dx.doi.org/10.1016/j.ultsonch.2020.105013DOI Listing
June 2020

Negative auto-regulation of sulfur dioxide generation in vascular endothelial cells: AAT1 S-sulfenylation.

Biochem Biophys Res Commun 2020 Feb 19. Epub 2020 Feb 19.

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

Recently, endogenous sulfur dioxide (SO) has been found to exert an important function in the cardiovascular system. However, the regulatory mechanism for SO generation has not been entirely clarified. Hence, we aimed to explore the possible auto-regulation of endogenous SO generation and its mechanisms in vascular endothelial cells. We showed that SO did not affect the protein expression of aspartate aminotransferase 1 (AAT1), a major SO synthesis enzyme, but significantly inhibited AAT activity in primary human umbilical vein endothelial cells (HUVECs) and porcine purified AAT1 protein. An AAT1 enzymatic kinetic study showed that SO reduced the Vmax (1.89 ± 0.10 vs 2.55 ± 0.12, μmol/mg/min, P < 0.05) and increased the Km (35.97 ± 9.54 vs 19.33 ± 1.76 μmol/L, P < 0.05) values. Furthermore, SO induced S-sulfenylation of AAT1 in primary HUVECs and purified AAT1 protein. LC-MS/MS analysis indicated that SO sulfenylated AAT1 at Cys192. Mechanistically, thiol reductant DTT treatment or C192S mutation prevented SO-induced AAT1 sulfenylation and the subsequent inhibition of AAT activity in purified AAT1 protein and primary HUVECs. Our findings reveal, for the first time, a mechanism of auto-regulation of SO generation through sulfenylation of AAT1 at Cys192 to suppress AAT activity in vascular endothelial cells. These findings will greatly deepen the understanding of regulatory mechanisms in the cardiovascular homeostasis.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.040DOI Listing
February 2020

Macrophage-derived sulfur dioxide is a novel inflammation regulator.

Biochem Biophys Res Commun 2020 04 10;524(4):916-922. Epub 2020 Feb 10.

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

Macrophage-mediated inflammation is a key pathophysiological component of cardiovascular diseases, but the underlying mechanisms by which the macrophage regulates inflammation have been unclear. In our study, we, for the first time, showed an endogenous sulfur dioxide (SO) production in RAW267.4 macrophages by using HPLC and SO-specific fluorescent probe assays. Moreover, the endogenous SO generating enzyme aspartate aminotransferase (AAT) was found to be expressed by the macrophages. Furthermore, we showed that AAT2 knockdown triggered spontaneous macrophage-mediated inflammation, as represented by the increased TNF-α and IL-6 levels and the enhanced macrophage chemotaxis; these effects could be reversed by the treatment with a SO donor. Mechanistically, AAT2 knockdown activated the NF-κB signaling pathway in macrophages, while SO successfully rescued NF-κB activation. In contrast, forced AAT2 expression reversed AngII-induced NF-κB activation and subsequent macrophage inflammation. Moreover, treatment with a SO donor also alleviated macrophage infiltration in AngII-treated mouse hearts. Collectively, our data suggest that macrophage-derived SO is an important regulator of macrophage activation and it acts as an endogenous "on-off switch" in the control of macrophage activation. This knowledge might enable a new therapeutic strategy for cardiovascular diseases.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.013DOI Listing
April 2020

Application of Electrochemical Aptasensors toward Clinical Diagnostics, Food, and Environmental Monitoring: Review.

Sensors (Basel) 2019 Dec 10;19(24). Epub 2019 Dec 10.

Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, India.

Aptamers are synthetic bio-receptors of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) origin selected by the systematic evolution of ligands (SELEX) process that bind a broad range of target analytes with high affinity and specificity. So far, electrochemical biosensors have come up as a simple and sensitive method to utilize aptamers as a bio-recognition element. Numerous aptamer based sensors have been developed for clinical diagnostics, food, and environmental monitoring and several other applications are under development. Aptasensors are capable of extending the limits of current analytical techniques in clinical diagnostics, food, and environmental sample analysis. However, the potential applications of aptamer based electrochemical biosensors are unlimited; current applications are observed in the areas of food toxins, clinical biomarkers, and pesticide detection. This review attempts to enumerate the most representative examples of research progress in aptamer based electrochemical biosensing principles that have been developed in recent years. Additionally, this account will discuss various current developments on aptamer-based sensors toward heavy metal detection, for various cardiac biomarkers, antibiotics detection, and also on how the aptamers can be deployed to couple with antibody-based assays as a hybrid sensing platform. Aptamers can be used in various applications, however, this account will focus on the recent advancements made toward food, environmental, and clinical diagnostic application. This review paper compares various electrochemical aptamer based sensor detection strategies that have been applied so far and used as a state of the art. As illustrated in the literature, aptamers have been utilized extensively for environmental, cancer biomarker, biomedical application, and antibiotic detection and thus have been extensively discussed in this article.
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http://dx.doi.org/10.3390/s19245435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960919PMC
December 2019

Vancomycin-resistance gene cluster, vanC, in the gut microbiome of acute leukemia patients undergoing intensive chemotherapy.

PLoS One 2019 10;14(10):e0223890. Epub 2019 Oct 10.

Department of Surgery, University of Minnesota, Minneapolis, MN, United States of America.

Two recent reports suggested that the less common, less virulent enterococcal species, Enterococcus gallinarum and E. casseliflavus, with low-level vancomycin resistance due to chromosomally encoded vanC1 and vanC2/3, may influence host immunity. We reported that peri-transplant gut colonization with E. gallinarum and E. casseliflavus is associated with lower mortality after allogeneic hematopoietic cell transplantation (HCT). Because most acute leukemia patients undergoing HCT have received intensive chemotherapy (usually requiring prolonged hospitalization) for their underlying disease before HCT, we hypothesized that some may have acquired vanC-positive enterococci during chemotherapy. Therefore, we evaluated the presence of the vanC gene cluster using vanC1 and vanC2/3 qPCR in thrice-weekly collected stool samples from 20 acute leukemia patients undergoing intensive chemotherapy. We found that an unexpectedly large proportion of patients have detectable vanC1 and vanC2/3 (15% and 35%, respectively) in at least one stool sample. Comparing qPCR results with 16S rRNA gene sequencing results suggested that E. gallinarum may reach high abundances, potentially persisting into HCT and influencing transplant outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223890PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786763PMC
March 2020

TiC MXene-Based Sensors with High Selectivity for NH Detection at Room Temperature.

ACS Sens 2019 10 11;4(10):2763-2770. Epub 2019 Oct 11.

School of Materials Science and Engineering , Henan Polytechnic University , Jiaozuo 454000 , China.

In this study, from experiments and theoretical calculation, we reported that TiC MXene can be applied as sensors for NH detection at room temperature with high selectivity. TiC MXene, a novel two-dimensional carbide, was prepared by etching off Al atoms from TiAlC. The as-prepared multilayer TiC MXene powders were delaminated to a single layer by intercalation and ultrasonic dispersion. The colloidal suspension of single-layer TiC-MXene was coated on the surface of ceramic tubes to construct sensors for gas detection. Thereafter, the sensors were used to detect various gases (CH, HS, HO, NH, NO, ethanol, methanol, and acetone) with a concentration of 500 ppm at room temperature. TiC MXene-based sensors have high selectivity to NH compared with other gases. The response to NH was 6.13%, which was four times the second highest response (1.5% to ethanol gas). To understand the high selectivity, first-principles calculations were conducted to explore adsorption behaviors. From adsorption energy, adsorbed geometry, and charge transfer, it was confirmed that TiC MXene theoretically has a high selectivity to NH, compared with other gases in this experiment. Moreover, the response of the sensor to NH increased almost linearly with NH concentration from 10 to 700 ppm. The humidity tests and cycle tests of NH showed that the TiC MXene-based gas sensor has excellent performances for NH detection at room temperature.
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http://dx.doi.org/10.1021/acssensors.9b01308DOI Listing
October 2019

Effects of biogenetic beliefs for schizophrenia on potential caregivers in China: Exploring the role of affiliate stigma.

Int J Ment Health Nurs 2020 Apr 27;29(2):161-170. Epub 2019 Sep 27.

Chinese Center for Disease Prevention and Control, Shibei District, Qingdao, China.

Schizophrenia affects more than eight million people in China. Stigmatization of schizophrenia may prevent family members and close others from providing social support to those with schizophrenia. This article aims to investigate the potential use of a biogenetic approach to reduce the stigma of schizophrenia using a cross-sectional (study 1, n = 141) and an experimental design (study 2, n = 100) in China. In the first study, mediation analysis reveals that perceived affiliate stigma, the negative prejudice, and discrimination towards family members of individuals with socially stigmatized identities due to their affiliation with the person mediates the path between biogenetic beliefs and desire for social distance. This pattern is replicated in study 2 in which two 10-min lectures were created and used to influence participants' beliefs in biogenetic causes of schizophrenia. Findings suggest that the biogenetic approach may increase Chinese participants' desired social distance towards their family members with schizophrenia through increasing their concerns about the negative consequences of being affiliated with the family member. Therefore, future research should investigate aspects of biogenetic anti-stigma campaigns that do not increase participants' perception of affiliate stigma in China.
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http://dx.doi.org/10.1111/inm.12655DOI Listing
April 2020

Applications of Hydrogels with Special Physical Properties in Biomedicine.

Polymers (Basel) 2019 Aug 29;11(9). Epub 2019 Aug 29.

School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai 201209, China.

As a polymer matrix containing a large amount of water, hydrogels have been widely used in many fields such as biology and medicine due to its similarity to extracellular matrix components, and its contact with blood, body fluids, and human tissue does not affect the metabolic processes of living organisms. However, due to the lack of unique physical properties of traditional polymer hydrogels, its further application in the high-end field is limited. With the progress of study, a series of hydrogels with special structures, such as double network hydrogel, composite hydrogel, Tetra-PEG gel, and topological gel, have improved the situation to a large extent. At the same time, the progress of research on the biocompatibility and biodegradability of hydrogels, which are expected to be used in biomedical fields, is also worthy of attention. This review introduces four such types of high-strength polymeric hydrogels and the mechanisms for improving their mechanical strength. Moreover, a discussion will be made around specific methods for imparting special physical properties to hydrogels and applications in the field of biomedicine such as cell culture, medical surgery, tissue engineering, and biosensing. At the end of the review, the main reasons and contradictions for the limits of the current applications are explained. An outlook on the future research in related fields and the importance of carrying out research in this area to promote medical progress are emphasized.
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http://dx.doi.org/10.3390/polym11091420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780509PMC
August 2019

Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies.

Sleep Med 2019 09 21;61:110-117. Epub 2019 Feb 21.

Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, PR China. Electronic address:

Objective: Restless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity.

Method: The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0.

Results: This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21-5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score.

Conclusion: The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.
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http://dx.doi.org/10.1016/j.sleep.2019.01.040DOI Listing
September 2019

Fluorescent Fluid in 3D-Printed Microreactors for the Acceleration of Photocatalytic Reactions.

Adv Sci (Weinh) 2019 Jul 26;6(13):1900583. Epub 2019 Apr 26.

School of Materials Science and Engineering Dalian University of Technology Dalian 116024 P. R. China.

The photochemical microreactor has been a burgeoning field with important application in promoting photocatalytic reactions. The integration of light-converting media and microflow chemistry renders new opportunity for efficient utilization of light and high conversion rate. However, the flexibility of emission light wavelength regulation and the universality of the microreactor remain significant problems to be solved. Here, a photochemical microreactor filled with fluorescent fluid is fabricated by a 3D printing technique. The light-converting medium in the fluorescent fluid is used to collect and convert light, and then delivers light energy to the embedded continuous-flow reaction channels to promote the chemical reaction process. With the merits of flowability, different light-converting media can be replaced, making it a general tool for photocatalytic reactions in rapid screening, parameters optimization, and kinetic mechanism research.
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http://dx.doi.org/10.1002/advs.201900583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662095PMC
July 2019

Synergistic effects of depression and obesity on type 2 diabetes incidence in Chinese adults.

J Diabetes 2020 Feb 9;12(2):142-150. Epub 2019 Jul 9.

Department of Public Health, University of Helsinki, Helsinki, Finland.

Background: Cross-sectional studies have supported the association among depression, obesity, and type 2 diabetes, but the causality remains controversial in Chinese adults. In this longitudinal study, we evaluated the synergistic effect of depression and obesity on the risk of type 2 diabetes.

Methods: This study included 2809 participants randomly selected from the Qingdao Diabetes Prevention Program, and their type 2 diabetes incidence was determined over a follow-up period of 3 years. The WHO 2006 criteria and the Zung Self-Rating Depression Scale score were employed to identify type 2 diabetes and depression at baseline, respectively. Multivariable-adjusted logistic regression was used to evaluate the synergistic effects of depression and obesity indicators on type 2 diabetes, with adjustment for age, sex, family history of diabetes, and other potential risk factors.

Results: During 3-year follow-up, 316 new incident cases were identified. The relative risk and 95% confidence interval of depression for diabetes incidence was 1.52 (1.05-2.21), after controlling for potential confounders. Sensitivity analysis showed that depression was significantly associated with diabetes incidence in women, younger people, and obese people (1.82 [1.14-2.92], 1.94 [1.25-3.02], and 4.29 [1.44-12.78], respectively]. The synergistic effects of positive depression and body mass index ≥30 kg/m on type 2 diabetes incidence were observed, with a synergy index of 5.49 (1.75-17.19).

Conclusions: Depression was associated with a 52% increased risk of type 2 diabetes incidence and exerts synergistic effects with obesity on diabetes incidence in Chinese adults. Early identification and intervention for depression and obesity can reduce the risk of diabetes.
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http://dx.doi.org/10.1111/1753-0407.12968DOI Listing
February 2020

Ultrasensitive ciprofloxacin assay based on the use of a fluorescently labeled aptamer and a nanocomposite prepared from carbon nanotubes and MoSe.

Mikrochim Acta 2019 07 3;186(8):507. Epub 2019 Jul 3.

School of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, 201209, China.

A nanocomposite was prepared from carbon nanotubes and MoSe (CNT-MoSe). This nanomaterial quenches the fluorescence of fluorescein-labeled aptamers. When ciprofloxacin (CIP) binds to the aptamer, an aptamer/G-quadruplex complex will be formed and the interaction between labeled aptamer and CNT-MoSe nanostructures is weakened. This leads to significant fluorescence recovery. Under optimized experimental conditions, the limit of detection is 0.63 ng mL with a good linearity in the range from 0.63 to 80 ng mL. The assay was applied to the determination of CIP in spiked milk, and the recoveries range between 94.3 and 97.0% (n = 3). Conceivably, the method is a generic approach that can be extended to the determination of other analyte for which adequate aptamers are available. Graphical abstract Schematic presentation of CNT-MoSe quenching based aptamer assay for the detection of ciprofloxacin. The assay exhibits good selectivity, stability and reproducibility, and low limit of detection.
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http://dx.doi.org/10.1007/s00604-019-3629-9DOI Listing
July 2019

Continuum percolation of congruent overlapping polyhedral particles: Finite-size-scaling analysis and renormalization-group method.

Phys Rev E 2019 Mar;99(3-1):032107

Materials Science and Engineering, Arizona State University, Tempe, Arizona 85287, USA.

The continuum percolation of randomly orientated overlapping polyhedral particles, including tetrahedron, cube, octahedron, dodecahedron, and icosahedron, was analyzed by Monte Carlo simulations. Two numerical strategies, (1) a Monte Carlo finite-size-scaling analysis and (2) a real-space Monte Carlo renormalization-group method, were, respectively, presented in order to determine the percolation threshold (e.g., the critical volume fraction ϕ_{c} or the critical reduced number density η_{c}), percolation transition width Δ, and correlation-length exponent ν of the polyhedral particles. The results showed that ϕ_{c} (or η_{c}) and Δ increase in the following order: tetrahedron < cube < octahedron < dodecahedron < icosahedron. In other words, both the percolation threshold and percolation transition width increase with the number of faces of the polyhedral particles as the shape becomes more "spherical." We obtained the statistical values of ν for the five polyhedral shapes and analyzed possible errors resulting in the present numerical values ν deviated from the universal value of ν=0.88 reported in literature. To validate the simulations, the corresponding excluded-volume bounds on the percolation threshold were obtained and compared with the numerical results. This paper has practical applications in predicting effective transport and mechanical properties of porous media and composites.
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http://dx.doi.org/10.1103/PhysRevE.99.032107DOI Listing
March 2019

Human bone marrow-derived mesenchymal stem cells promote the growth and drug-resistance of diffuse large B-cell lymphoma by secreting IL-6 and elevating IL-17A levels.

J Exp Clin Cancer Res 2019 Feb 12;38(1):73. Epub 2019 Feb 12.

Department of Blood Transfusion, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Panfu Rd No.1, Yuexiu District, Guangzhou, 510180, Guangdong, China.

Background: The drug-resistance and relapse of diffuse large B-cell lymphoma (DLBCL), which are related to mesenchymal stem cells (MSCs), have become increasingly common. However, the underlying mechanisms remain elusive.

Methods: CCK 8 assay, colony formation assay, and xenograft mouse model were used to investigate the effects of hBMSCs on DLBCL growth. Immunohistochemistry, qRT-PCR, and ELISA were used to study the expressions of IL-6 and IL-17A. Flow cytometry was used to analyze Th17 cells and Treg cells expressions. Western blot analysis, microarray analysis, and bioinformatics analysis were used to analyze the pathways of IL-6 or IL-17A mediated DLBCL growth.

Results: HBMSCs promoted DLBCL growth by secreting IL-6 in vitro and in vivo and simultaneously upregulating IL-17A in vitro. IL-6 and IL-17A synergistically promoted the growth and drug-resistance of DLBCL cells by protecting them from spontaneous or drug-induced apoptosis in vitro. IL-6 or IL-17A activated the JAK2/STAT3 pathway or upregulated cyclin D2 via activation of PI3K/Akt signaling in vitro, respectively.

Conclusions: The present results indicated that hBMSCs might have a "dual effect" on promoting DLBCL progression and drug-resistance by secreting IL-6 and upregulating IL-17A. IL-6, IL-17A, p-STAT3, p-Akt or cyclin D2 may be potential molecular targets for overcoming drug-resistance in patients with relapsed or refractory DLBCL.
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http://dx.doi.org/10.1186/s13046-019-1081-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373150PMC
February 2019

Surface biofunctionalization of the decellularized porcine aortic valve with VEGF-loaded nanoparticles for accelerating endothelialization.

Mater Sci Eng C Mater Biol Appl 2019 Apr 26;97:632-643. Epub 2018 Dec 26.

Department of cardiovascular surgery, the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

The original intention for building a tissue-engineered heart valve (TEHV) was to simulate a normal heart valve and overcome the insufficiency of the commonly used heart valve replacement in the clinic. The endothelialization of the TEHV is very important as the endothelialized TEHV can decrease platelet adhesion and delay the valvular calcification decline process. In this work, we encapsulated vascular endothelial growth factor (VEGF) into polycaprolactone (PCL) nanoparticles. Then, through the Michael addition reaction, PCL nanoparticles were introduced onto the decellularized aortic valve to prepare a hybrid valve. The encapsulation efficiency of the PCL nanoparticles for VEGF was up to 82%, and the in vitro accumulated release rate was slow without an evident initial burst release. In addition, the hybrid valve had a decreased hemolysis ratio and possessed antiplatelet adhesion capacity, and it was able to promote the adhesion and proliferation of endothelial cells, covering the surface with a dense cell layer to accelerate endothelialization. An experiment involving the subcutaneous implant in SD rats showed that at week 8, lots of blood capillaries were formed in the hybrid valve. Mechanics performance testing indicated that the mechanical property of the hybrid valve was partly improved. Taken together, we applied a nano-drug controlled release system to fabricate TEHV, and provide an approach for the biofunctionalization of the TEHV scaffold for accelerating endothelialization.
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http://dx.doi.org/10.1016/j.msec.2018.12.079DOI Listing
April 2019

Knockdown of PSMC3IP suppresses the proliferation and xenografted tumorigenesis of hepatocellular carcinoma cell.

J Cell Biochem 2019 04 25;120(4):5449-5458. Epub 2018 Oct 25.

Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy and the second leading cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) is an oncogene in breast cancer, while its role in HCC remains unclear. Here, we found that PSMC3IP was critical for the cell proliferation and tumorigenic capacity of HCC cells. Upregulation of PSMC3IP was observed in HCC specimens, and high PSMC3IP expression predicted poor overall survival of HCC patients. In vitro, knockdown of PSMC3IP blunted the proliferation and colony formation of BEL-7404 and SMMC-7721 cells. Likewise, PSMC3IP silencing suppressed the xenografted tumor development of BEL-7404 cells. Mechanistically, apoptosis was enhanced after PSMC3IP knockdown in both BEL-7404 and SMMC-7721 cells. At the molecular level, TP53 and GNG4 were upregulated and eukaryotic translation initiation factor 4E (EIF4E) and insulin like growth factor 1 receptor (IGF1R) were downregulated in shPSMC3IP compared with shCtrl BEL-7404 cells. Therefore, targeting PSMC3IP maybe a promising strategy for HCC.
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http://dx.doi.org/10.1002/jcb.27824DOI Listing
April 2019
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