Publications by authors named "Jinghua Zhang"

106 Publications

A State-of-the-Art Review for Gastric Histopathology Image Analysis Approaches and Future Development.

Biomed Res Int 2021 26;2021:6671417. Epub 2021 Jun 26.

Microscopic Image and Medical Image Analysis Group, College of Medicine and Biological Information Engineering, Northeastern University, Shenyang 110169, China.

Gastric cancer is a common and deadly cancer in the world. The gold standard for the detection of gastric cancer is the histological examination by pathologists, where Gastric Histopathological Image Analysis (GHIA) contributes significant diagnostic information. The histopathological images of gastric cancer contain sufficient characterization information, which plays a crucial role in the diagnosis and treatment of gastric cancer. In order to improve the accuracy and objectivity of GHIA, Computer-Aided Diagnosis (CAD) has been widely used in histological image analysis of gastric cancer. In this review, the CAD technique on pathological images of gastric cancer is summarized. Firstly, the paper summarizes the image preprocessing methods, then introduces the methods of feature extraction, and then generalizes the existing segmentation and classification techniques. Finally, these techniques are systematically introduced and analyzed for the convenience of future researchers.
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http://dx.doi.org/10.1155/2021/6671417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257332PMC
June 2021

Network pharmacology-based and molecular docking prediction of the active ingredients and mechanism of ZaoRenDiHuang capsules for application in insomnia treatment.

Comput Biol Med 2021 Jun 18;135:104562. Epub 2021 Jun 18.

Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beixiange 5, Xicheng District, Beijing, 100053, China. Electronic address:

Background: The ZaoRenDiHuang (ZRDH) capsule is widely used in clinical practice and has significant therapeutic effects on insomnia. However, its active ingredients and mechanisms of action for insomnia remain unknown. In this study, network pharmacology was employed to elucidate the potential anti-insomnia mechanisms of ZRDH.

Methods: The potential active ingredients of ZRDH were obtained from the Traditional Chinese Medicine Systems Pharmacology Database. Possible targets were predicted using SwissTargetPrediction tools. The insomnia-related targets were identified using the therapeutic target database, Drugbank database, Online Mendelian Inheritance in Man database, and gene-disease associations database. A compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using the Metascape platform.

Results: In this study, 61 anti-insomnia components and 65 anti-insomnia targets of ZRDH were filtered through database mining. The drug-disease network was constructed with five key components. Sixty-five key targets were identified using topological analysis. Docking studies indicated that bioactive compounds could stably bind to the pockets of target proteins. Through data mining and network analysis, the GO terms and KEGG annotation suggested that the neuroactive ligand-receptor interaction, serotonergic synapse CAMP signaling, HIF-1a signaling, and toll-like receptor signaling pathways play vital roles against insomnia.

Conclusion: The potential mechanisms of ZRDH treatment for insomnia involve multiple components, targets, and pathways. These findings provide a reference for further investigations into the mechanisms underlying ZRDH treatment of insomnia.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104562DOI Listing
June 2021

A nano-predator of pathological MDMX construct by clearable supramolecular gold(I)-thiol-peptide complexes achieves safe and potent anti-tumor activity.

Theranostics 2021 3;11(14):6833-6846. Epub 2021 May 3.

Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

As alternatives to small-molecular proteolysis-targeting chimeras (PROTAC), peptide-based molecular glues (MG) are a broad range of dual-functional ligands that simultaneously bind with targetable proteins and E3 ligases by mimicking proteinprotein interaction (PPI) partners. Herein, we design a peptide-derived MG to target a tumor-driving protein, MDMX, for degradation, and nanoengineered it into a supramolecular gold(I)-thiol-peptide complex (Nano-MP) to implement the proteolysis recalcitrance, cellular internalization, and glutathione-triggered release. To optimize the tumor targeting, a pH-responsive macromolecule termed polyacryl sulfydryl imidazole (PSI) was synthesized to coat Nano-MP. As expected, [email protected] induced the MDMX degradation by ubiquitination and subsequently restored the anti-cancer function of p53 and p73. [email protected] revealed potent anti-cancer activities in an orthotopic xenograft mouse model of retinoblastoma by intraocular injection and a patient-derived xenograft model of malignant pancreatic cancer by systemic injection, while maintaining a favorable safety profile and showing a highly favorable clearable profile of excretion from the living body. Collectively, this work not only provided a clinically viable paradigm for the treatment of a wide variety of tumors by multiple administration types, but, more importantly, it bridged the chasm between peptides and PROTACs, and likely reinvigorated the development of peptide-derived proteolysis-targeting chimeras for a great variety of diseases.
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http://dx.doi.org/10.7150/thno.59020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171083PMC
May 2021

Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer.

Front Oncol 2021 28;11:657483. Epub 2021 Apr 28.

Health Science Center, The First Affiliated Hospital of Shenzhen University, and Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, Shenzhen, China.

Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.
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http://dx.doi.org/10.3389/fonc.2021.657483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114939PMC
April 2021

EMDS-5: Environmental Microorganism image dataset Fifth Version for multiple image analysis tasks.

PLoS One 2021 12;16(5):e0250631. Epub 2021 May 12.

School of Control Engineering, Chengdu University of Information Technology, Chengdu, China.

Environmental Microorganism Data Set Fifth Version (EMDS-5) is a microscopic image dataset including original Environmental Microorganism (EM) images and two sets of Ground Truth (GT) images. The GT image sets include a single-object GT image set and a multi-object GT image set. EMDS-5 has 21 types of EMs, each of which contains 20 original EM images, 20 single-object GT images and 20 multi-object GT images. EMDS-5 can realize to evaluate image preprocessing, image segmentation, feature extraction, image classification and image retrieval functions. In order to prove the effectiveness of EMDS-5, for each function, we select the most representative algorithms and price indicators for testing and evaluation. The image preprocessing functions contain two parts: image denoising and image edge detection. Image denoising uses nine kinds of filters to denoise 13 kinds of noises, respectively. In the aspect of edge detection, six edge detection operators are used to detect the edges of the images, and two evaluation indicators, peak-signal to noise ratio and mean structural similarity, are used for evaluation. Image segmentation includes single-object image segmentation and multi-object image segmentation. Six methods are used for single-object image segmentation, while k-means and U-net are used for multi-object segmentation. We extract nine features from the images in EMDS-5 and use the Support Vector Machine (SVM) classifier for testing. In terms of image classification, we select the VGG16 feature to test SVM, k-Nearest Neighbors, Random Forests. We test two types of retrieval approaches: texture feature retrieval and deep learning feature retrieval. We select the last layer of features of VGG16 network and ResNet50 network as feature vectors. We use mean average precision as the evaluation index for retrieval. EMDS-5 is available at the URL:https://github.com/NEUZihan/EMDS-5.git.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250631PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116046PMC
May 2021

Function of Small Peptides During Male-Female Crosstalk in Plants.

Front Plant Sci 2021 23;12:671196. Epub 2021 Apr 23.

College of Life Sciences, National Key Laboratory of Wheat and Maize Crop Science, Henan Agricultural University, Zhengzhou, China.

Plant peptides secreted as signal molecular to trigger cell-to-cell signaling are indispensable for plant growth and development. Successful sexual reproduction in plants requires extensive communication between male and female gametophytes, their gametes, and with the surrounding sporophytic tissues. In the past decade, it has been well-documented that small peptides participate in many important reproductive processes such as self-incompatibility, pollen tube growth, pollen tube guidance, and gamete interaction. Here, we provide a comprehensive overview of the peptides regulating the processes of male-female crosstalk in plant, aiming at systematizing the knowledge on the sexual reproduction, and signaling of plant peptides in future.
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http://dx.doi.org/10.3389/fpls.2021.671196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102694PMC
April 2021

Filamentous target segmentation of weft micro-CT image based on U-Net.

Micron 2021 Jul 27;146:102923. Epub 2021 Feb 27.

School of Mechanical and Electrical Engineering, Guangdong University of Technology (GDUT), China.

Textile fabrics inspection is an important part of textile manufacturing industry, more and more new inspections technologies are adopted for the application. Micro CT imaging technology is recently explored for textile material inspection. This paper proposed a method of weft micro-CT image segmentation based on U-Net, by using deep learning theory and X-ray micro-CT nondestructive detection technology to realize automatic segmentation of filamentous objects. Firstly, the weft micro-CT image was obtained by X-ray micro-CT scan, and then the segmentation target was manually divided. A high segmentation accuracy CT image segmentation dataset of textile materials was built for training the network model. Based on the original U-Net, through experimental exploration, the attention mechanism was introduced, and the encoder module, decoder module and loss function module were adjusted, so as to get a good segmentation effect. The experimental results show that the segmentation performance superiority of this proposed algorithm and the Dice similarity coefficient reaches 0.843. The method proposed in this paper provides a direction for the combination of deep learning technology and micro-CT technology in industrial detection.
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http://dx.doi.org/10.1016/j.micron.2020.102923DOI Listing
July 2021

Assessing carbamazepine and oxcarbazepine-associated Stevens-Johnson syndrome/toxic epidermal necrolysis: Data mining the public version of the FDA adverse event reporting system.

Int J Clin Pract 2021 Aug 17;75(8):e14273. Epub 2021 May 17.

Department of Pharmacy, Chongqing University Three Gorges Hospital, Chongqing, P.R. China.

Aims: Stevens-Johnson syndrome and toxic epidermal necrolysis are viewed as the most severe drug-induced types of cutaneous adverse reactions, with high rates of morbidity and mortality. We aimed to examine carbamazepine- and oxcarbazepine-associated Stevens-Johnson syndrome or toxic epidermal necrolysis, by data mining the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: Reports in FAERs were analysed, from the first quarter of 2004 to the last quarter of 2019. Pharmacovigilance tools were employed for the quantitative detection of signals, where a signal represents a drug-associated adverse event, including the reporting odds ratio, proportional reporting ratio, an information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean.

Results: The total number of reports identified as Stevens-Johnson syndrome or toxic epidermal necrolysis associated with carbamazepine or oxcarbazepine included in this study was 1231. FAERS reports associated with carbamazepine were 1048, including Stevens-Johnson syndrome (n = 668) and toxic epidermal necrolysis(n = 380). FAERS reports associated with oxcarbazepine were 183, including 142 Stevens-Johnson syndrome and 41 toxic epidermal necrolysis reports. The risk for Stevens-Johnson syndrome is higher than for toxic epidermal necrolysis and carbamazepine is associated with a higher risk than oxcarbazepine.

Conclusions: The results of our study are consistent with clinical observations, suggesting the necessity for further clinical research on Stevens-Johnson syndrome and toxic epidermal necrolysis associated with carbamazepine or oxcarbazepine.
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http://dx.doi.org/10.1111/ijcp.14273DOI Listing
August 2021

Synthesis and in vitro antibacterial activity of new aminothiazole-oximepiperidone cephalosporins.

Bioorg Med Chem Lett 2021 05 8;40:127928. Epub 2021 Mar 8.

Yunnan Baiyao Group Co., Ltd., 3686 Yunnan Baiyao Street, Kunming 650200, PR China.

Four new aminothiazole-oximepiperidone cephalosporins (10a-10d) were synthesized, with their in vitro antibacterial activities against hospital isolated Gram-negative bacteria assessed. The results showed that compounds 10a-10d effectively inhibit a variety of Gram-negative bacteria. Compound 10a was the most potent compound, with comparable activity as ceftazidime. The combination of compound 10a and Avibactam was very active against almost all bacteria tested, which including multidrug resistant K. pneumoniae and A. baumannii. Compared to Avycaz, this combination is more potent against ESBL producing K. pneumoniae. Thus, the combination of 10a and Avibactam is of interest for further studies.
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http://dx.doi.org/10.1016/j.bmcl.2021.127928DOI Listing
May 2021

Combined effects of polyethylene and organic contaminant on zebrafish (Danio rerio): Accumulation of 9-Nitroanthracene, biomarkers and intestinal microbiota.

Environ Pollut 2021 May 16;277:116767. Epub 2021 Feb 16.

School of Environment, Nanjing Normal University, Jiangsu Engineering Lab of Water and Soil Eco-Remediation, Nanjing, 210023, China; Green Economy Development Institute, Nanjing University of Finance and Economics, Nanjing, 210023, China. Electronic address:

Microplastics, as emerging pollutant, are predicted to act as carriers for organic pollutants, but the carrier role and bio-toxic effects with other pollutants in environments are poorly acknowledged. In this study, both the single and combined effects of polyethylene (PE, 10 and 40 mg/L) with the particle size of 100-150 μm and 9-Nitroanthracene (9-NAnt, 5 and 500 μg/L) on zebrafish (Danio rerio) had been investigated. The results illustrated that PE could be as 9-NAnt carrier to enter into zebrafish body, but significantly reduced the bioaccumulation of 9-NAnt, due to the occurrence of adsorption interactions between the simultaneous presence of both PE and 9-NAnt. After 4 days, the enzymes activity of cytochrome P4501A, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), and the abundance of malondialdehyde (MDA), lipid peroxide (LPO) responded strongly to low-dose PE exposure (10 mg/L). After 7 days exposure to PE-9-NAnt (40 mg/L), the P4501A activity increased significantly, but the activities of AChE and LDH were inhibited clearly, causing certain neurotoxicity and disorders of energy metabolism to zebrafish. The analysis of integrated biomarker response index (IBR) suggested that PE had greater bio-toxicity to zebrafish in all exposure groups after short-term exposure, but the PE-9-NAnt complex showed greater bio-toxicity after 7 days, which indicated that complex exposure of PE-9-NAnt had a delayed effect on the bio-toxicity of zebrafish. Furthermore, analysis of the intestinal microbiota exhibited that under the conditions of the exposure group with 9-NAnt, the relative abundance of the five dominant bacterial phyla (Proteobacteria, Firmicutes, Fusobacteriota, Bacteroidota and Verrucomicrobiota) changed greatly. Overall, this study confirmed that PE could carry 9-NAnt into fish causing bioaccumulation, but in the case of coexisting exposures, PE reduced 9-NAnt bioaccumulation, suggesting that microplastics with other emerging pollutants in chronic toxicity are probably next objects in future works.
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http://dx.doi.org/10.1016/j.envpol.2021.116767DOI Listing
May 2021

Purification of recombinant human chemokine CCL2 in and its function in ovarian cancer.

3 Biotech 2021 Jan 2;11(1). Epub 2021 Jan 2.

College of Life Sciences, Henan Agricultural University, Zhengzhou, 450002 China.

Chemokine (CC-motif) ligand 2 (CCL2) is an inflammatory cytokine that regulates the infiltration and migration of monocytes. It is highly expressed by both tumor and stromal cells and has been associated with tumorigenesis. However, the effect of the exogenous administration of CCL2 on ovarian cancer remains largely unknown. In this report, we attempted to establish an expression system in to produce recombinant hCCL2. The recombinant plasmid containing the hCCL2 cDNA was prepared using the prokaryotic-expression plasmid pGEX-5X-3 and transformed into BL21. GST-hCCL2 was successfully induced by 0.1 mmol/L IPTG at 20 °C for 6 h, and the recombinant protein was purified using affinity chromatography. The purified protein was identified by SDS-PAGE and Western Blot. In vitro experiments revealed that rhCCL2 promoted the proliferation of ovarian cancer cells and increased the levels of phosphorylation of MEK and ERK1/2, and the levels of JUN, RELB and NF-κB2 mRNA. Furthermore, inhibition of ERK signaling by treatment with PD98059 decreased ovarian cancer cell proliferation and levels of JUN, RELB, and NF-κB2 mRNA, indicating that exogenous rhCCL2 increased the proliferation of ovarian cancer cells, partially by activating the MAPK/ERK pathway, and by targeting JUN, RELB, and NF-κB2. Our study uncovered a promoting role of exogenous CCL2 on ovarian cancer cell proliferation through the MAPK/ERK signaling pathway, which may facilitate the discovery of more potential roles of CCL2 in ovarian cancer.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-020-02571-0.
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http://dx.doi.org/10.1007/s13205-020-02571-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778648PMC
January 2021

Penalized Quadratic Inference Function-Based Variable Selection for Generalized Partially Linear Varying Coefficient Models with Longitudinal Data.

Comput Math Methods Med 2020 5;2020:3505306. Epub 2020 Oct 5.

College of Applied Sciences, Beijing University of Technology, Beijing, China.

Semiparametric generalized varying coefficient partially linear models with longitudinal data arise in contemporary biology, medicine, and life science. In this paper, we consider a variable selection procedure based on the combination of the basis function approximations and quadratic inference functions with SCAD penalty. The proposed procedure simultaneously selects significant variables in the parametric components and the nonparametric components. With appropriate selection of the tuning parameters, we establish the consistency, sparsity, and asymptotic normality of the resulting estimators. The finite sample performance of the proposed methods is evaluated through extensive simulation studies and a real data analysis.
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http://dx.doi.org/10.1155/2020/3505306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556090PMC
July 2021

Subcellular localization of the porcine deltacoronavirus nucleocapsid protein.

Virus Genes 2020 Dec 17;56(6):687-695. Epub 2020 Sep 17.

Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, 1101 Zhimin Dadao, Qingshan Lake District, Nanchang, 330045, Jiangxi, China.

Porcine deltacoronavirus (PDCoV) has been recently identified as an emerging enteropathogenic coronavirus that mainly infects newborn piglets and causes enteritis, diarrhea and high mortality. Although coronavirus N proteins have multifarious activities, the subcellular localization of the PDCoV N protein is still unknown. Here, we produced mouse monoclonal antibodies against the PDCoV N protein. Experiments using anti-haemagglutinin antibodies and these monoclonal antibodies revealed that the PDCoV N protein is shuttled into the nucleolus in both ectopic PDCoV N-expressing cells and PDCoV-infected cells. The results of deletion mutagenesis experiments demonstrated that the predicted nucleolar localization signal at amino acids 295-318 is critical for nucleolar localization. Cumulatively, our study yielded a monoclonal antibody against the PDCoV N protein and revealed a mechanism by which the PDCoV N protein translocated into the nucleolus. The tolls and findings from this work will facilitate further investigations on the functions of the PDCoV N protein.
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http://dx.doi.org/10.1007/s11262-020-01790-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497858PMC
December 2020

Effect of Antibiotics on Gut and Vaginal Microbiomes Associated with Cervical Cancer Development in Mice.

Cancer Prev Res (Phila) 2020 12 11;13(12):997-1006. Epub 2020 Sep 11.

Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.

Antibiotics affect microbial diversity in the gut, leading to dysbiosis and impaired immunity. However, the impact of antibiotics on microbial communities at other sites, such as vagina is less understood. It is also not clear whether changes induced by antibiotics in both microbiomes affect the development of cervical cancer. In this study, we utilized the murine model to evaluate these questions. We show that oral application of broad-spectrum antibiotics in mice changed not only diversity, but composition and sharing of gut and vaginal microbiomes in mice and influenced cervical cancer development in an orthotopic tumor model. Antibiotics decreased richness and diversity indexes in the gut but increased them in the vagina. Some beneficial taxa, such as , and increased their abundance in the vagina while other pathogenic species, such as , were decreased. As a result of the changes, mice with greater richness and diversity of the vaginal microbiome after antibiotics exposure were less likely developed tumors. No association between richness and diversity of the gut microbiome and tumor development was identified.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0103DOI Listing
December 2020

A Multiscale CNN-CRF Framework for Environmental Microorganism Image Segmentation.

Biomed Res Int 2020 7;2020:4621403. Epub 2020 Jul 7.

Microscopic Image and Medical Image Analysis Group, MBIE College, Northeastern University, Shenyang 110169, China.

To assist researchers to identify Environmental Microorganisms (EMs) effectively, a (MSCC) framework for the EM image segmentation is proposed in this paper. There are two parts in this framework: The first is a novel pixel-level segmentation approach, using a newly introduced (CNN), namely, "mU-Net-B3", with a dense (CRF) postprocessing. The second is a VGG-16 based patch-level segmentation method with a novel "buffer" strategy, which further improves the segmentation quality of the details of the EMs. In the experiment, compared with the state-of-the-art methods on 420 EM images, the proposed MSCC method reduces the memory requirement from 355 MB to 103 MB, improves the overall evaluation indexes (Dice, Jaccard, Recall, Accuracy) from 85.24%, 77.42%, 82.27%, and 96.76% to 87.13%, 79.74%, 87.12%, and 96.91%, respectively, and reduces the volume overlap error from 22.58% to 20.26%. Therefore, the MSCC method shows great potential in the EM segmentation field.
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http://dx.doi.org/10.1155/2020/4621403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366198PMC
April 2021

A solid-phase extraction method for estrogenic disrupting compounds based on the estrogen response element.

Food Chem 2020 Dec 9;333:127529. Epub 2020 Jul 9.

Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, Key Laboratory of Food Nutrition and Safety of Shandong Normal University, College of Life Science, Shandong Normal University, Jinan 250014, PR China. Electronic address:

A solid-phase extraction (SPE) method for enriching and purifying estrogenic disrupting compounds (EDCs) based on the estrogen response element was established. The estrogen receptor was used for molecular recognition, as it specifically binds EDCs. An estrogen response element was used to maintain the activity of the estrogen receptor. High-performance liquid chromatography (HPLC) was used to quantify the EDCs. This method combined with HPLC was applied to detect three kinds of EDCs, such as bisphenol A (BPA), 17β-estradiol, and diethylstilbestrol in a liquid milk matrix, with recoveries of 84.1 ± 8.2% to 113.6 ± 2.9%. The limits of detection and quantification of the established method were 1 × 10 mg·mL and 5 × 10 mg·mL. The method was further applied to analyze market samples, including liquid milk, fermented milk, and milk powder. Only BPA was detected from one brand of liquid milk and it was below the regulatory level.
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http://dx.doi.org/10.1016/j.foodchem.2020.127529DOI Listing
December 2020

Studies on the stereoselective synthesis and immunosuppressive activity of dihydroartemisinin-O-glycoside derivatives.

Bioorg Med Chem Lett 2020 08 10;30(16):127338. Epub 2020 Jun 10.

Shanghai Jiao Tong University School of Medicine, PR China; Shanghai University of Traditional Chinese Medicine, PR China. Electronic address:

Eight new dihydroartemisinin-O-glycosides were synthesized with their relative configurations were determined based on NMR spectrum. In vitro immunosuppressive assay showed that 10α-dihydroartemisinin-β-O-d-mannoside (19a) demonstrate 88% inhibition towards T cells proliferation and 98% reduction in IFN-γ levels in cell media. These results suggest that dihydroartemisinin-O-glycoside as a potential lead for further in vivo evaluation.
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http://dx.doi.org/10.1016/j.bmcl.2020.127338DOI Listing
August 2020

Large-Scale Discovery of Non-conventional Peptides in Maize and Arabidopsis through an Integrated Peptidogenomic Pipeline.

Mol Plant 2020 07 21;13(7):1078-1093. Epub 2020 May 21.

National Key Laboratory of Wheat and Maize Crop Science, Collaborative Innovation Center of Henan Grain Crops, College of Agronomy, Henan Agricultural University, Zhengzhou 450002, China. Electronic address:

Non-conventional peptides (NCPs), which include small open reading frame-encoded peptides, play critical roles in fundamental biological processes. In this study, we developed an integrated peptidogenomic pipeline using high-throughput mass spectra to probe a customized six-frame translation database and applied it to large-scale identification of NCPs in plants.A total of 1993 and 1860 NCPs were unambiguously identified in maize and Arabidopsis, respectively. These NCPs showed distinct characteristics compared with conventional peptides and were derived from introns, 3' UTRs, 5' UTRs, junctions, and intergenic regions. Furthermore, our results showed that translation events in unannotated transcripts occur more broadly than previously thought. In addition, we found that dozens of maize NCPs are enriched within regions associated with phenotypic variations and domestication selection, indicating that they potentially are involved in genetic regulation of complex traits and domestication in maize. Taken together, our study developed an integrated peptidogenomic pipeline for large-scale identification of NCPs in plants, which would facilitate global characterization of NCPs from other plants. The identification of large-scale NCPs in both monocot (maize) and dicot (Arabidopsis) plants indicates that a large portion of plant genome can be translated into biologically functional molecules, which has important implications for functional genomic studies.
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http://dx.doi.org/10.1016/j.molp.2020.05.012DOI Listing
July 2020

Melodinhenine B attenuates NLRP3 expression in a cerebral ischemia/reperfusion-induced neuronal injury rat model.

Folia Neuropathol 2020 ;58(1):30-37

Department of Neurology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.

This investigation evaluated the neuroprotective effect of melodinhenine B in a cerebral ischemia/reperfusion (I/R)-induced neuronal injury rat model. The effect of melodinhenine B was determined by evaluating the neurological deficit score, cerebral infarcted area, and blood-brain barrier (BBB) permeability. Moreover, the level of inflammatory cytokines and expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), interleukin-1β (IL-1β), NLRP3, zonula occludens-1 (ZO-1), and occluding proteins were estimated by Western blotting. Histopathological changes and immunohistochemical analysis were performed to estimate the effect of melodinhenine B on neuronal injury. The neurological deficit score, percentage of infarcted area, and BBB permeability were improved in the melodinhenine B-treated group of rats. Treatment with melodinhenine B attenuated the altered expression of NF-κβ, IL-1β, NLRP3, ZO-1, and occluding proteins in the brain tissue of I/R-induced neuronal injury rats. The inflammatory cytokine levels were reduced in the melodinhenine B-treated group. Histopathologically, melodinhenine B reversed the pathological changes in the brain tissues of I/R-induced neuronal injury rats. In conclusion, melodinhenine B protects against neuronal injury in cerebral ischemia-reperfusion injury rats by regulating the inflammasomes.
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http://dx.doi.org/10.5114/fn.2020.94004DOI Listing
February 2021

The Developmental Enhancement of a C System With Non-Typical C Physiological Characteristics in (Kranz Anatomy), an Annual Desert Halophyte.

Front Plant Sci 2020 6;11:152. Epub 2020 Mar 6.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.

Variations of photosynthetic structures in different tissues or cells are in coordination with changes in various aspects, e.g. physiology, biochemistry, gene expression, etc. Most C plant species undergo developmental enhancement of the photosynthetic system, which may present different modes of changes between anatomy and physiology/biochemistry. In the current study, we investigated a Kranz-type C species with the progressive development of photosynthetic (PS) structure, performance of PS physiology, induction of PS enzymes, and transcriptional and translational regulation of PS genes, results revealed that presented C type anatomy in cotyledons but C type in leaves (C/L), with the C system separation of initial carbon fixation in the palisade mesophyll (M) cells and the following incorporation into triosephosphates and sugars in the bundle sheath (BS) cells, respectively. The BS cells continuously surrounded the vascular bundles and water storage cells in leaf anatomic structure. Compared to the single-cell C species , exhibited similar developmental enhancement of C syndrome temporally and spatially in anatomic structures, enzyme activities, and gene expression, which suggests that completion of differentiation of the photosynthetic system is necessary for a C assimilation pathway. Besides, also displayed some different characteristics compared to in photosynthetic physiology, e.g. a more flexible δC value, much lower phosphoenolpyruvate carboxylase (PEPC) activity, and an insensitive response to stimuli, etc., which were not typical C characteristics. We speculate that this may suggest a different status of these two species in the evolutionary process of the photosynthesis pathway. Our findings will contribute to further understanding of the diversity of photosynthesis systems in Kranz-type C species and the genus.
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http://dx.doi.org/10.3389/fpls.2020.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069449PMC
March 2020

Heterologous Expression of CLIBASIA_03915/CLIBASIA_04250 by Resulted in Phloem Necrosis in the Senescent Leaves of .

Int J Mol Sci 2020 Feb 19;21(4). Epub 2020 Feb 19.

College of Agronomy and Biotechnology, Southwest University, Chongqing 400715, China.

Huanglongbing (HLB), also known as citrus greening, is the most notorious citrus disease worldwide. Liberibacter asiaticus (Las) is a phloem-restricted bacterium associated with HLB. Because there is no mutant library available, the pathogenesis of Las is obscure. In this study, we employed TMV) to express two mature secretion proteins CLIBASIA_03915 (m03915) and CLIBASIA_04250 (m04250) in (). Phloem necrosis was observed in the senescent leaves of that expressed the two low molecular weight proteins, while no phloem necrosis was observed in the plants that expressed the control, green fluorescent protein (GFP). Additionally, no phloem necrosis was observed in the senescent leaves of that expressed the null mutation of m03915 and frameshifting m04250. The subcellular localizations of m03915 and m04250 were determined by fusion with GFP using confocal microscopy. The subcellular localization of m03915 was found to be as free GFP without a nuclear localization sequence (NLS). However, m04250 did have an NLS. Yeast two-hybrid (Y2H) was carried out to probe the citrus proteins interacting with m03915 and m04250. Six citrus proteins were found to interact with m03915. The identified proteins were involved in the metabolism of compounds, transcription, response to abiotic stress, ubiquitin-mediated protein degradation, etc. The prey of m04250 was involved in the processing of specific pre-mRNAs. Identification of new virulence factors of Las will give insight into the pathogenesis of Las, and therefore, it will eventually help develop the HLB-resistant citrus.
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http://dx.doi.org/10.3390/ijms21041414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073121PMC
February 2020

Adsorption behavior and mechanism of 9-Nitroanthracene on typical microplastics in aqueous solutions.

Chemosphere 2020 Apr 16;245:125628. Epub 2019 Dec 16.

Green Economy Development Institute, Nanjing University of Finance and Economics, Nanjing, 210023, PR China; Jiangsu Engineering Lab of Water and Soil Eco-remediation, Nanjing Normal University, Nanjing, 210023, PR China. Electronic address:

Microplastics and Nitropolycyclic aromatic hydrocarbons (NPAHs) are two types of emerging pollutants that are strong potential threats to aquatic ecosystems and organisms. The adsorption of NPAHs on microplastics may explain the fate and effects of NPAHs in natural environments. In this study, the adsorption behavior of 9-Nitroanthrene (9-NAnt) on polyethylene (PE), polypropylene (PP) and polystyrene (PS) was investigated. Kinetic experiments revealed that 9-NAnt was inclined to be adsorbed onto microplastics, especially PE, which had a large adsorption amount of 734 μg g. A linear isothermal model better described the isothermal adsorption process for 9-NAnt, which indicated that a hydrophobic distribution may be the main adsorption mechanism in an aqueous solution. Water environment factors, such as the pH and ionic strength, had negligible effects on the adsorption for PE. In contrast, alkaline and high ionic strength conditions resulted in the inhibition of adsorption of PP and PS. In addition, the particle size of microplastics was negatively correlated with the log K of 9-NAnt, and the performance of transient aging treatments on microplastics reduced their affinity for 9-NAnt, due to the addition of oxygen-containing functional groups. Above all, hydrophobic and electrostatic processes were the main adsorption mechanisms between microplastics and 9-NAnt.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125628DOI Listing
April 2020

Abnormal expression of chondroitin sulfate sulfotransferases in the articular cartilage of pediatric patients with Kashin-Beck disease.

Histochem Cell Biol 2020 Mar 16;153(3):153-164. Epub 2019 Dec 16.

Department of Integrative Medical Biology, Umeå University, 90187, Umeå, Sweden.

The objective of this study is to investigate the expression of enzymes involved in the sulfation of articular cartilage from proximal metacarpophalangeal (PMC) joint cartilage and distal metacarpophalangeal (DMC) joint cartilage in children with Kashin-Beck disease (KBD). The finger cartilage samples of PMC and DMC were collected from KBD and normal children aged 5-14 years old. Hematoxylin and eosin staining as well as immunohistochemical staining were used to observe the morphology and quantitate the expression of carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), uronyl 2-O-sulfotransferase (UST), and aggrecan. In the results, the numbers of chondrocyte decreased in all three zones of PMC and DMC in the KBD group. Less positive staining cells for CHST-3, CHST-12, CHST-13, UST, and aggrecan were observed in almost all three zones of PMC and DMC in KBD. The positive staining cell rates of CHST-12 were higher in superficial and middle zones of PMC and DMC in KBD, and a significantly higher rate of CHST-13 was observed only in superficial zone of PMC in KBD. In conclusion, the abnormal expression of chondroitin sulfate sulfotransferases in chondrocytes of KBD children may provide an explanation for the cartilage damage, and provide therapeutic targets for the treatment.
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http://dx.doi.org/10.1007/s00418-019-01833-0DOI Listing
March 2020

Identification of the Virulence Factors of Liberibacter asiaticus via Heterologous Expression in using .

Int J Mol Sci 2019 Nov 8;20(22). Epub 2019 Nov 8.

College of Agronomy and Biotechnology, Southwest University, Beibei, Chongqing 400715, China.

Huanglongbing (HLB), also known as citrus greening, is the most destructive disease of citrus worldwide. HLB is associated with the non-culturable bacterium, Liberibacter asiaticus (Las) in the United States. The virulence mechanism of Las is largely unknown, partly because of the lack of a mutant library. In this study, (TMV) and () were used for large-scale screening of the virulence factors of Las. Agroinfiltration of 60 putative virulence factors in led to the identification of four candidates that caused severe symptoms in , such as growth inhibition and cell death. CLIBASIA_05150 and CLIBASIA_04065C (C-terminal of CLIBASIA_04065) could cause cell death in the infiltrated leaves at five days post infiltration. Two low-molecular-weight candidates, CLIBASIA_00470 and CLIBASIA_04025, could inhibit plant growth. By converting start codon to stop codon or frameshifting, the four genes lost their harmful effects to . It indicated that the four virulence factors functioned at the protein level rather than at the RNA level. The subcellular localization of the four candidates was determined by confocal laser scanning microscope. CLIBASIA_05150 located in the Golgi apparatus; CLIBASIA_04065 located in the mitochondrion; CLIBASIA_00470 and CLIBASIA_04025 distributed in cells as free GFP. The host proteins interacting with the four virulence factors were identified by yeast two-hybrid. The host proteins interacting with CLIBASIA_00470 and CLIBASIA_04025 were overlapping. Based on the phenotypes, the subcellular localization and the host proteins identified by yeast two-hybrid, CLIBASIA_00470 and CLIBASIA_04025, functioned redundantly. The hypothesis of Las virulence was proposed. Las affects citrus development and suppresses citrus disease resistance, comprehensively, in a complicated manner. Ubiquitin-mediated protein degradation might play a vital role in Las virulence. Deep characterization of the interactions between the identified virulence factors and their prey will shed light on HLB. Eventually, it will help in developing HLB-resistant citrus and save the endangered citrus industry worldwide.
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http://dx.doi.org/10.3390/ijms20225575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888081PMC
November 2019

Geniposide Alleviates Traumatic Brain Injury in Rats Via Anti-Inflammatory Effect and MAPK/NF-kB Inhibition.

Cell Mol Neurobiol 2020 May 1;40(4):511-520. Epub 2019 Nov 1.

Heze Municipal Hospital of Shandong Province, No. 2888 Caozhou Road, Mudan District, Heze, 274000, Shandong, China.

We aimed to investigate whether geniposide, a main component extracted from Gardenia jasminoides Ellis fruit, could exert neuroprotective functions against traumatic brain injury (TBI). Enzyme-linked immunosorbent assay (ELISA) was used for detection of plasma cytokines. Real-time polymerase chain reaction (RT-PCR) was employed for measurements of mRNA levels of cytokines. Neurological outcomes were evaluated by modified neurological severity score (mNSS) and Rota-Rod. Blood-brain barrier (BBB) integrity and brain edema were assessed. Protein expression was tested by Western blot. The plasma levels of interleukin (IL)-1β, IL-6, IL-8 and IL-10 were all elevated in patients with TBI compared to those of healthy controls. TBI rats treated with geniposide showed lower mNSS and longer fall latency time than untreated TBI rats. BBB integrity was maintained and brain edema was reduced by geniposide treatment in TBI rats. Plasma levels of IL-1β, IL-6 and IL-8 were significantly repressed by geniposide treatment in TBI rats, whereas IL-10 level was upregulated. mRNA expression levels of these cytokines in the brain tissues of TBI rats exhibited the same trends of changes. By testing p38 mitogen-activated protein kinase and NF-κB p65 activities, it was observed that phosphorylated (p)-p38 and p-p65 were dramatically inhibited by geniposide. In conclusion, geniposide exerts neuroprotective functions against TBI by inhibiting p-p38 and p-p65.
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http://dx.doi.org/10.1007/s10571-019-00749-6DOI Listing
May 2020

Electrospun Sesbania Gum-Based Polymeric -Halamines for Antibacterial Applications.

Polymers (Basel) 2019 Jul 1;11(7). Epub 2019 Jul 1.

College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, China.

Microorganism pollution induced by pathogens has become a serious concern in recent years. In response, research on antibacterial -halamines has made impressive progress in developing ways to combat this pollution. While synthetic polymer-based -halamines have been widely developed and in some cases even commercialized, -halamines based on naturally occurring polymers remain underexplored. In this contribution, we report for the first time on a strategy for developing sesbania gum (SG)-based polymeric -halamines by a four-step approach Using SG as the initial polymer, we obtained SG-based polymeric -halamines (abbreviated as cSG-PAN nanofibers) via a step-by-step controllable synthesis process. With the assistance of advanced techniques, the as-synthesized cSG-PAN nanofibers were systematically characterized in terms of their chemical composition and morphology. In a series of antibacterial and cytotoxicity evaluations, the as-obtained cSG-PAN nanofibers displayed good antibacterial activity against and , as well as low cytotoxicity towards A549 cells. We believe this study offers a guide for developing naturally occurring polymer-based antibacterial -halamines that have great potential for antibacterial applications.
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http://dx.doi.org/10.3390/polym11071117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680915PMC
July 2019

Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR-204 expression.

Basic Clin Pharmacol Toxicol 2019 Nov 17;125(5):450-459. Epub 2019 Jul 17.

Department of Oncology, Heze Municipal Hospital, Heze, China.

Gastric carcinoma (GC) is a pernicious neoplasm with high morbidity and mortality. Sinomenine (SIN) has long been exploited to heal rheumatoid arthritis. Recently, SIN has been discovered to exert the antitumour functions in diverse cancers. However, the impacts of SIN on GC remain indistinct. We attempted to expose the antitumour effect of SIN on GC. MKN45 and SGC-7901 cells were administered with SIN for 24 hours, cell viability, proliferation, apoptosis, migration, invasion and the associated proteins in the above processes were examined via exploiting CCK-8, BrdU, flow cytometry, Transwell and Western blot. MiR-204 expression in GC tumour tissues, different GC cell lines and SIN-stimulated GC cells was investigated by executing RT-qPCR. The above cell biological processes were reassessed after transfection with miR-204 inhibitor. The latent mechanisms were probed by examining AMPK and Wnt/β-catenin pathways. We found that SIN memorably repressed cell proliferation, evoked apoptosis and affected CyclinD1, Bcl-2, Bax and cleaved-caspase-3 expression in MKN45 and SGC-7901 cells. Cell migration, invasion and expression of MMP-9 and Vimentin were all restrained by SIN stimulation. The increase of miR-204 was discovered in GC tissues and SIN-treated MKN45 and SGC-7901 cells. But suppression of miR-204 was observed in AGS, MKN28, MKN45 and SGC-7901 cells. Suppression of miR-204 overturned the inhibitory functions of SIN in MKN45 and SGC-7901 cells. Besides, SIN prohibited AMPK and Wnt/β-catenin pathways via enhancement of miR-204. In conclusion, these findings suggested that SIN exerted the antitumour activity in GC cells by hindering AMPK and Wnt/β-catenin pathways via enhancement of miR-204.
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http://dx.doi.org/10.1111/bcpt.13285DOI Listing
November 2019

Direct detection of potassium and lead (II) ions based on assembly-disassembly of a chiral cyanine dye /TBA complex.

Talanta 2019 Aug 14;201:490-495. Epub 2019 Apr 14.

National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Beijing National Laboratory for Molecular Sciences (BNLMS), Beijing, 100190, PR China. Electronic address:

A highly selective and sensitive direct detection of potassium (K) and lead (Pb) ions was developed by using the assembly and disassembly of a chiral cyanine dye/TBA complex. The dye DMSB (3-ethyl-2-[3-(3-ethyl-3H-benzoselenazol-2-ylidene)-2-methylprop-1-enyl] benzoselenazolium bromide) loses the ability of self-assembly, but it can be activated by thrombin-binding aptamer (TBA) G-quadruplex structure. And only the TBA G-quadruplex formed in the presence of K, can strongly induce J-aggregate signals of DMSB. Because the Pb ions can bind and stabilize the TBA G-quadruplex with much higher efficiency than K, the J-aggregate signals of DMSB falls sharply when the Pb is present. As a result, the assembly and disassembly of DMSB allows the selective detection of 10 μM K and 20 nM Pb respectively, even the competitive sodium ion (Na) was as high as 145 mM. The linear correlation existed between the J-aggregate intensity and the concentration of K and Pb over the range of 0.5-5.0 mM and 200-2000 nM, respectively. Moreover, the concentration of K (∼3 mM) and Pb (below 20 nM) in human blood serum samples were determined by the present method, which agreed well with inductively coupled plasma mass spectrometry (ICP-MS). This work not only opens a door for the further development of G-quadruplex-based aptasensor in complex real system, but also provides a simple and versatile sensing platform for ion detection in clinic.
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http://dx.doi.org/10.1016/j.talanta.2019.04.032DOI Listing
August 2019

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice.

Exp Biol Med (Maywood) 2019 06 1;244(9):721-727. Epub 2019 May 1.

1 Department of Clinical Laboratory, Zhejiang Shaoxing Shangyu People's Hospital, Shaoxing 312353, P. R. China.

Impact Statement: Acute lung injury (ALI), a common complication of many serious health issues, such as serious infection, burns, and shock, is one of the most common critical illnesses in clinical practice with a high mortality rate of 30-40%. There are still short of effective prevention and treatment measures. Evidence is growing that hydrogen-rich saline (HRS) may be an effective drug for the prevention and treatment of ALI. However, the mechanisms involved in have not been clearly understood. In this study, we investigated the underling mechanisms by focusing on autophagy regulation. The results showed that HRS ameliorated lipopolysaccharide-induced ALI in mice by inhibiting autophagy over-activation through ROS/AMPK/mTOR pathway. HRS may be a new therapeutic strategy for ALI prevention and treatment in the future.
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http://dx.doi.org/10.1177/1535370219847941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567588PMC
June 2019

Loss of expression promotes malignant phenotypes and correlates with poor prognosis in renal carcinoma.

Cancer Manag Res 2019 7;11:1211-1220. Epub 2019 Feb 7.

Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China,

Background: belongs to the inwardly rectifying potassium channel (KIR) family. Although members of the KIR family have been proven to play important roles in a variety of developmental processes, the molecular role and clinical effects of in cancers remain unclear.

Purpose: The aim of this study was to identify the expression, biological functions and molecular mechanisms of in renal cell carcinoma (RCC).

Methods: mRNA expression was evaluated in kidney cancer tissue, paired adjacent normal tissue, and cell lines with qRT-PCR. protein expression was investigated via western blotting and immunohistochemistry. In addition, the clinical and prognostic significance of in RCC were assessed using Kaplan-Meier analysis and Cox proportional hazards analysis. In vitro, the effects of on kidney cancer cells were evaluated by means of a cell counting kit-8, transwell assay along with flow cytometry, respectively. Moreover, the potential mechanism of was demonstrated by Western blot.

Results: Here, we first found that was significantly downregulated in RCC, and this low expression was an independent prognostic factor for clear cell RCC (ccRCC). Moreover, was associated with advanced TNM stage (n=150, =0.014) and histological grade (n=150, =0.045). Furthermore, overexpression significantly inhibited RCC cell proliferation, migration, and colony formation, arrested the cell cycle and induced apoptosis of RCC cells in vitro. The inhibitory effect of overexpression may be regulated by its effects on the epithelial mesenchymal transition (EMT) process and matrix metalloproteinase (MMP)-7 and p21 expression.

Conclusion: These findings indicate that may be a tumor suppressor in RCC and a possible target for RCC therapy.
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http://dx.doi.org/10.2147/CMAR.S184368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369858PMC
February 2019
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