Publications by authors named "Shulin Zhang"

102 Publications

Light limitation inducing overcompensatory growth of cyanobacteria and function of serine/threonine kinase (STK) genes involved.

Water Sci Technol 2021 Mar;83(6):1347-1356

Key Laboratory of Aquatic-Ecology and Aquaculture of Tianjin, College of Fishery, Tianjin Agricultural University, Tianjin, China E-mail:

The rapid overcompensatory growth that appears when cyanobacteria are supplied with adequate resources after a period of resource deprivation might contribute to the occurrence of cyanobacterial blooms. We investigated the changing characteristics of overcompensatory growth and serine/threonine kinase (STK) genes expression of cyanobacterium Microcystis aeruginosa in response to light limitation. The results showed M. aeruginosa exhibited overcompensatory growth for 2 days after light recovery, during which the increase in growth was inversely related to light intensity. Expression of STK genes, such as spkD, was upregulated significantly at 0.5-4 h after light recovery (P < 0.05). To investigate the function of STK genes in the overcompensatory growth, M. aeruginosa spkD was heterologously expressed in Synechocystis. Transgenic Synechocystis exhibited greater and longer overcompensatory growth than wild-type Synechocystis after light recovery. Relative expression levels of STK genes in transgenic Synechocystis were significantly higher than those in wild-type Synechocystis at 24 h of light recovery (P < 0.05). Heterologous expression of Microcystis spkD might stimulate overcompensatory growth of Synechocystis by affecting its STK gene expression.
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http://dx.doi.org/10.2166/wst.2021.071DOI Listing
March 2021

A high proportion of novel ACAN mutations and their prevalence in a large cohort of Chinese short stature children.

J Clin Endocrinol Metab 2021 Feb 19. Epub 2021 Feb 19.

Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital, Children's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Context: Aggrecan, encoded by ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. Heterozygous mutations in ACAN have been reported to cause idiopathic short stature. However, the prevalence of ACAN pathogenic variants in Chinese short stature patients and clinical phenotypes remain to be evaluated.

Objective: We sought to determine the prevalence of ACAN pathogenic variants among Chinese short stature children and characterize the phenotypic spectrum and their responses to growth hormone (GH) therapies.

Patients And Methods: Over 1000 unrelated short stature patients ascertained across China were genetically evaluated by Next-generation sequencing (NGS)-based test.

Result: We identified 10 novel likely pathogenic variants and 2 recurrent pathogenic variants in this cohort. None of ACAN mutation carriers exhibited significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect is estimated to be 1.2% in the whole cohort, it increased to 14.3% among those with advanced bone age and to 35.7% among those with both advanced bone age and family history of short stature. Nonetheless, five out of eleven ACAN mutation carries had no advanced bone age. Two individuals received growth hormone therapy with variable levels of height SDS improvement.

Conclusion: Our data suggested that ACAN mutation is one of the common causes of Chinese pediatric short stature. Although it has a higher detection rate among short stature patients with advanced bone age and family history, part of affected probands presented with delayed bone age in Chinese short stature population. The growth hormone treatment was moderately effective for both individuals.
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http://dx.doi.org/10.1210/clinem/dgab088DOI Listing
February 2021

Multi-omic dissection of the drought resistance traits of soybean landrace LX.

Plant Cell Environ 2021 Feb 8. Epub 2021 Feb 8.

State Key Laboratory of Crop Stress Adaptation and Improvement, Henan Joint International Laboratory for Crop Multi-Omics Research, School of Life Sciences, Henan University, Kaifeng, China.

With diverse genetic backgrounds, soybean landraces are valuable resource for breeding programs. Herein, we apply multi-omic approaches to extensively characterize the molecular basis of drought tolerance in the soybean landrace LX. Initial screens established that LX performed better with PEG6000 treatment than control cultivars. LX germinated better than William 82 under drought conditions and accumulated more anthocyanin and flavonoids. Untargeted mass spectrometry in combination with transcriptomic analyses revealed the chemical diversity and genetic basis underlying the overall performance of LX landrace. Under control and drought conditions, significant differences in the expression of a suite of secondary metabolism genes, particularly those involved in the general phenylpropanoid pathway and flavonoid but not lignin biosynthesis, were seen in LX and William 82. The expression of these genes correlated with the corresponding metabolites in LX plants. Further correlation analysis between metabolites and transcripts identified pathway structural genes and transcription factors likely are responsible for the LX agronomic traits. The activities of some key biosynthetic genes or regulators were confirmed through heterologous expression in transgenic Arabidopsis and hairy root transformation in soybean. We propose a regulatory mechanism based on flavonoid secondary metabolism and adaptive traits of this landrace which could be of relevance to cultivated soybean.
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http://dx.doi.org/10.1111/pce.14025DOI Listing
February 2021

Dynamic changes of transcriptome of fifth-instar larvae in response to insecticide.

3 Biotech 2021 Feb 27;11(2):98. Epub 2021 Jan 27.

School of Biology and Food-Engineering, Anyang Institute of Technology, Anyang, 455000 China.

is a major insect with a cosmopolitan distribution and strong resistance to multiple insecticides. Determining the molecular basis and key candidate genes of the insecticide resistance of may help in managing this insect. In this study, fifth-instar larvae were subjected to transcriptome analysis at 6, 12, 24, 48, and 72 h after feeding on an LC20 dose of avermectin. The result showed that genes responding to avermectin changed dynamically with different gene counts and resistance mechanisms at the fifth instar based on a metabolic pathway map. These responses included degrading the insecticide by a series of P450 and glutathione-S-transferase enzymes starting at the 12 h time point, with subsequent increases in the number of genes involved and shifts to TOLL and immune deficiency (IMD) pathways at 48 h after feeding the insecticide. Weighted correlation network analysis (WGCNA) determined a co-expression module related to the avermectin response at 12 and 24 h  = 0.403,  = 0.0371;  = 0.436,  = 0.023), in which a hub gene () related to metalloproteinase activity was identified. In addition, Analysis of the genes in the co-expression module further revealed that eight genes encoding UDP-glucuronosyltransferases were directly associated with insecticide response in . These results provide better understanding of the avermectin response mechanism of and may be useful in developing improved control strategies for this species.

Supplementary Information: The online version of this article (10.1007/s13205-021-02651-9) contains supplementary material, which is available to authorized users.
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http://dx.doi.org/10.1007/s13205-021-02651-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840824PMC
February 2021

Analysis of the effect of postpartum rehabilitation nursing on the management of postpartum depression.

J Pak Med Assoc 2020 Sep;70 [Special Issue](9):9-15

Department of Obstetrics and Gynecology, Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China.

Objective: To study the effect of postpartum rehabilitation nursing on the management of postpartum depression.

Methods: A total of 100 primiparas were randomly selected in this study. They were divided into postpartum nursing intervention group (50 cases) and control group (50 cases). The data from prenatal and postpartum women were collected through questionnaires. The Edinburgh postpartum depression scale, social support scale, general self-efficacy scale, and mother's role adaptation questionnaire were distributed to 100 pregnant women. By collecting the results of these questionnaires, the differences between the nursing intervention group and the control group were compared.

Results: The results showed that the proportion of postpartum depression in 50 primiparas after postpartum rehabilitation nursing was significantly lower than that of the control group. The physiological and psychological changes of primipara after childbirth would be significant, and would be subject to tremendous pressure from all aspects.

Conclusions: This change and pressure were the main causes of postpartum depression in primipara. Postpartum rehabilitation nursing can effectively alleviate primipara's postpartum depression.
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September 2020

Impact of tea polyphenols on the stability of oil-in-water emulsions coated by whey proteins.

Food Chem 2021 May 23;343:128448. Epub 2020 Oct 23.

Department of Food Science, University of Massachusetts, Amherst, MA 01003, United States. Electronic address:

The ability of tea polyphenols (0, 0.01, 0.02 or 0.04 w/v %) to inhibit lipid and protein oxidation in walnut oil-in-water (O/W) emulsions was examined, as well as to alter their stability to aggregation and creaming. The lipid droplets in these emulsions were coated by whey proteins. The physical stability of the emulsions during storage (50 °C, 96 h) was improved by addition of 0.01% tea polyphenols, but reduced when higher levels were added. Low levels (0.01%) of tea polyphenols inhibited lipid oxidation (lipid hydroperoxide and 2-thiobarbituric acid-reactive substance formation) and protein oxidation (carbonyl and Schiff base formation, sulfhydryl and intrinsic fluorescence loss, and molecular weight changes). However, high levels (0.04%) of tea polyphenols were less effective at inhibiting lipid oxidation, and actually promoted protein oxidation. Tea polyphenols are natural antioxidants that can enhance the quality and shelf life of emulsified polyunsaturated lipids when used at an appropriate concentration.
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http://dx.doi.org/10.1016/j.foodchem.2020.128448DOI Listing
May 2021

Effectiveness of magnetocardiography to identify patients in need of coronary artery revascularization: a cross-sectional study.

Cardiovasc Diagn Ther 2020 Aug;10(4):831-840

Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai, China.

Background: Patients with angina-like symptoms need invasive or non-invasive angiography to determine whether revascularization is necessary. For patients in need of revascularization, undergoing coronary computed tomography angiography (CCTA) may delay the treatment of revascularization and increase exposure to contrast agents and radiation. The aim of this cross-sectional study was to accessed the effectiveness of magnetocardiography (MCG) to identify patients who should undergo coronary revascularization.

Methods: A total of 203 patients who were suffering from angina-like symptoms and underwent percutaneous coronary angiography (PCA) between July 27, 2015 and April 10, 2017 at the 8th Medical Center of Chinese PLA General Hospital, were enrolled in this cross-sectional study. In all patients, 12-lead electrocardiography (ECG) and MCG test were performed before PCA. For each subject. The value at every single sampling point was extracted from T wave of each MCG channel in time sequence. Pearson's correlation coefficients were calculated for each two T-waves. A binary logistic regression diagnosis model of these coefficients was established to identify patients in need of revascularization.

Results: Ten pairings of coefficients were entered into diagnostic regression model as covariates. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.747 (95% CI: 0.680-0.815), and the asymptotic P value was less than 0.001. At the cut-off value of 0.55, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72.9%, 65.9%, 74.8%, 63.6% and 69.9%, and the positive and negative post-test probabilities were 65.9% and 25.7%. The accuracy, sensitivity, specificity, PPV and NPV for 12-lead ECG were 67.0%, 62.7%, 63.5%, 70.5% and 55.1%, respectively. However, when those acute myocardial infarction (AMI) patients were ruled out from both groups, the MCG model had an accuracy of 68.2%, a sensitivity of 70.1%, a specificity of 66.3%, a PPV of 68.5% and an NPV of 67.9%. But, the accuracy, sensitivity, specificity, PPV and NPV for 12-lead ECG were 60.0%, 55.2%, 65.1%, 62.3% and 58.1%, respectively.

Conclusions: Patients suffering from angina-like symptoms, with a logistic regression model value over 0.55, should be recommended for PCA.
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http://dx.doi.org/10.21037/cdt-20-121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487377PMC
August 2020

Clinical and laboratory interpretation of mitochondrial mRNA variants.

Hum Mutat 2020 Jul 11. Epub 2020 Jul 11.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

Interpretation of mitochondrial protein-encoding (mt-mRNA) variants has been challenging due to mitochondrial characteristics that have not been addressed by American College of Medical Genetics and Genomics guidelines. We developed criteria for the interpretation of mt-mRNA variants via literature review of reported variants, tested and refined these criteria by using our new cases, followed by interpreting 421 novel variants in our clinical database using these verified criteria. A total of 32 of 56 previously reported pathogenic (P) variants had convincing evidence for pathogenicity. These variants are either null variants, well-known disease-causing variants, or have robust functional data or strong phenotypic correlation with heteroplasmy levels. Based on our criteria, 65.7% (730/1,111) of variants of unknown significance (VUS) were reclassified as benign (B) or likely benign (LB), and one variant was scored as likely pathogenic (LP). Furthermore, using our criteria we classified 2, 12, and 23 as P, LP, and LB, respectively, among 421 novel variants. The remaining stayed as VUS (91.2%). Appropriate interpretation of mt-mRNA variants is the basis for clinical diagnosis and genetic counseling. Mutation type, heteroplasmy levels in different tissues of the probands and matrilineal relatives, in silico predictions, population data, as well as functional studies are key points for pathogenicity assessments.
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http://dx.doi.org/10.1002/humu.24082DOI Listing
July 2020

Pathogenic Prion Protein Isoforms Are Not Present in Cerebral Organoids Generated from Asymptomatic Donors Carrying the E200K Mutation Associated with Familial Prion Disease.

Pathogens 2020 Jun 18;9(6). Epub 2020 Jun 18.

Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Division of Intramural Research, Rocky Mountain Laboratories, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.

Cerebral organoids (COs) are a self-organizing three-dimensional brain tissue mimicking the human cerebral cortex. COs are a promising new system for modelling pathological features of neurological disorders, including prion diseases. COs expressing normal prion protein (PrPC) are susceptible to prion infection when exposed to the disease isoforms of PrP (PrPD). This causes the COs to develop aspects of prion disease pathology considered hallmarks of disease, including the production of detergent-insoluble, protease-resistant misfolded PrPD species capable of seeding the production of more misfolded species. To determine whether COs can model aspects of familial prion diseases, we produced COs from donor fibroblasts carrying the E200K mutation, the most common cause of human familial prion disease. The mature E200K COs were assessed for the hallmarks of prion disease. We found that up to 12 months post-differentiation, E200K COs harbored no PrPD as confirmed by the absence of detergent-insoluble, protease-resistant, and seeding-active PrP species. Our results suggest that the presence of the E200K mutation within the prion gene is insufficient to cause disease in neuronal tissue. Therefore, other factors, such as further genetic modifiers or aging processes, may influence the onset of misfolding.
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http://dx.doi.org/10.3390/pathogens9060482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350378PMC
June 2020

Response to Bai et al.

Genet Med 2020 08 18;22(8):1420-1421. Epub 2020 May 18.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

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http://dx.doi.org/10.1038/s41436-020-0805-6DOI Listing
August 2020

Study on Electron-Induced Surface Plasmon Coupling with Quantum Well Using a Perturbation Method.

Nanomaterials (Basel) 2020 May 9;10(5). Epub 2020 May 9.

State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China.

Ag nanoparticles (NPs) are filled in a photonic crystal (PhC) hole array on green light emitting diodes (LEDs). The localized surface plasmon (LSP)-quantum well (QW) coupling effect is studied by measuring the cathodoluminescence (CL) spectra impinging at the specific spots on the Ag NPs. Twenty-six percent and fifty-two percent enhancements of the CL intensities are obtained at the center and edge of the Ag NP, respectively, compared to the result that the electron-beam (e-beam) excites the QW directly. To illustrate the coupling process of the three-body system of e-beam-LSP-QW, a perturbation theory combining a three-dimensional (3D) finite difference time domain (FDTD) simulation is put forward. The effects of the polarization orientation of the dipole and the field symmetry of the LSP on the LSP-QW coupling are also discussed.
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http://dx.doi.org/10.3390/nano10050913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279149PMC
May 2020

The Apoptosis Mechanism of Epirubicin Combined with BCG on Human Bladder Cancer Cells.

Anticancer Agents Med Chem 2020 ;20(13):1571-1581

School of Bioscience and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Aims: The purpose of our study was to explore the combination effect of epirubicin and Bacillus Calmette Guerin (BCG) and its mechanism.

Background: Bladder cancer is a threat to human health worldwide. Commonly used chemotherapy drugs and biotherapy have significant therapeutic effects on bladder cancer, but the mechanism and combined effects are still unclear.

Objective: To evaluate the anti-cancer effect of epirubicin combined with BCG on human bladder cancer cells, our studies were carried out.

Methods: The viability of human bladder cancer cells with epirubicin and/or BCG treatments was examined by Cell Counting Kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl-2) were detected by western blot.

Results: The viability of human bladder cancer with epirubicin or BCG treatment was decreased and the viability with epirubicin combined with BCG treatment was decreased more, which were determined by CCK-8 assay. Both epirubicin and BCG increased the apoptosis rate of human bladder cancer and arrested more cells into G0/G1 phase, which were tested by flow cytometry. The expression of caspase-3, p53 and Bax was increased and the expression of Bcl-2 was decreased with epirubicin treatment on human bladder cells, which were analyzed by western blot. The expression of caspase-3 and p53 was increased with BCG treatment, which was examined by western blot.

Conclusion: Epirubicin induced apoptosis in human bladder cancer cells by up-regulating the expression of proapoptotic factors (caspase-3, p53 and Bax) and down-regulating the expression of anti-apoptotic factor (Bcl-2). BCG promoted apoptosis of human bladder cancer cells by up-regulating the expression of caspase-3 and p53. BCG plays a potential role at the time of the combination of epirubicin and BCG on bladder cancer cells in early stage. Both epirubicin and BCG affected cell cycle distribution via arresting more bladder cancer cells at G0/G1 phase, which ultimately led bladder cancer proliferation in vitro and promoted apoptosis.
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http://dx.doi.org/10.2174/1871520620666200502004002DOI Listing
January 2020

The current status of malignant hyperthermia.

J Biomed Res 2019 May;34(2):75-85

Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA 95817, USA.

Malignant hyperthermia (MH) is a rare and life-threatening pharmacogenetic disorder triggered by volatile anesthetics, the depolarizing muscle relaxant succinylcholine, and rarely by strenuous exercise or environmental heat. The exact prevalence of MH is unknown, and it varies from 1:16 000 in Denmark to 1:100 000 in New York State. The underlying mechanism of MH is excessive calcium release from the sarcoplasmic reticulum (SR), leading to uncontrolled skeletal muscle hyper-metabolism. Genetic mutations in ryanodine receptor type 1 ( ) and have been identified in approximately 50% to 86% and 1% of MH-susceptible (MHS) individuals, respectively. Classic clinical symptoms of MH include hypercarbia, sinus tachycardia, masseter spasm, hyperthermia, acidosis, muscle rigidity, hyperkalemia, myoglobinuria, and There are two types of testing for MH: a genetic test and a contracture test. Contracture testing is still being considered as the gold standard for MH diagnosis. Dantrolene is the only available drug approved for the treatment of MH through suppressing the calcium release from SR. Since clinical symptoms of MH are highly variable, it can be difficult to establish a diagnosis of MH. Nevertheless, prompt diagnosis and treatments are crucial to avoid a fatal outcome. Therefore, it is very important for anesthesiologists to raise awareness and understand the characteristics of MH. This review summarizes epidemiology, clinical symptoms, diagnosis and treatments of MH and any new developments.
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http://dx.doi.org/10.7555/JBR.33.20180089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183298PMC
May 2019

Correction: Interpretation of mitochondrial tRNA variants.

Genet Med 2020 Jun;22(6):1130

Department of Molecular and Human Genetics, , Baylor College of Medicine, Houston, TX, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41436-020-0802-9DOI Listing
June 2020

Inhibition evaluation of gas inhibitors in micron-sized aluminum dust explosion.

J Hazard Mater 2020 07 18;393:122524. Epub 2020 Mar 18.

School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning, 116024, PR China. Electronic address:

The inhibition effects of gas inhibitors (nitrogen, carbon dioxide, and heptafluoropropane) on aluminum dust explosion were investigated experimentally and numerically. The results showed that as the inhibition volume fraction increased, the flame propagation characteristics parameters and explosion severity parameters were inhibited by inert gases accordingly. The inhibition performance of carbon dioxide was superior to that of nitrogen, and the minimum inhibition volume fractions of nitrogen and carbon dioxide were determined. XRD results indicated that the crystal form of major condensed product of aluminum dust explosion using two kinds of inert gas as inhibitors was different due to the distinct inhibition effect. Moreover, the XPS analysis revealed that the nitrogen oxide of aluminum adsorbed on the surface of aluminum particles blocked gasification process of aluminum particles. To explore the inhibition mechanism microscopically, a kinetic model concerning gas phase combustion was established. The above discussion indicated that the inhibition effect was the combination of multiple factors. In addition, due to the strong reactions between aluminum particles and heptafluoropropane, it cannot be regarded as gas inhibitor in aluminum dust explosion.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122524DOI Listing
July 2020

CpG Oligodeoxynucleotides Induces Apoptosis of Human Bladder Cancer Cells via Caspase-3-Bax/Bcl-2-p53 Axis.

Arch Med Res 2020 04 3;51(3):233-244. Epub 2020 Mar 3.

School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address:

Objective: To evaluate the anti-cancer effect of unmethylated cytosine-phosphorothioate-guanine (CpG)-containing oligodeoxynucleotides (ODNs) on human bladder cancer UM-UC-3 cells, our study was carried out.

Methods: The viability of cells (UM-UC-3, T24 and SV-HUC-1) with CpG ODN treatments was examined by cell counting kit-8 (CCK-8) assay. Apoptosis and cell cycle phase were determined by flow cytometry analysis. Pre-apoptosis factors of caspase-3, p53, B-cell lymphoma 2 associated X protein (Bax) and anti-apoptosis factor of B-cell lymphoma 2 (Bcl-2) were detected by western blot.

Results: Experimental results showed that the viability of human bladder cancer cells (UM-UC-3 and T24) with CpG ODN treatment was decreased and the viability of human normal urothelial cells (SV-HUC-1) with CpG ODN treatment was increased with time-dependance manner. Moreover, CpG ODN increased the apoptosis rate of UM-UC-3 cells and arrested more cells in G0G1 phase. Furthermore, the expression of caspase-3, p53 and Bax were increased and the expression of Bcl-2 was decreased with CpG ODN treatment on UM-UC-3 cells.

Conclusion: CpG ODN promoted the proliferation of normal urinary transitional epithelial cells (SV-HUC-1) and inhibited the cell viability of human bladder cancer cells (UM-UC-3 and T24) in vitro. CpG ODN induced the apoptosis of human bladder cancer (UM-UC-3) cells in a cascade progress via enhancing the expression of caspase-3, p53 and Bax, and inhibiting the expression of Bcl-2 with significant time-dependancy. CpG ODN inhibited cell cycle distribution of human bladder cancer (UM-UC-3) cells with more cells were arrested in G0G1 phase. This study suggested that the CpG ODN is the potential candidate on human bladder cancer.
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http://dx.doi.org/10.1016/j.arcmed.2020.02.005DOI Listing
April 2020

Correction: Interpretation of mitochondrial tRNA variants.

Genet Med 2020 May;22(5):979

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41436-020-0770-0DOI Listing
May 2020

Application of a Y-type-DNA-functionalized nanogold probe featuring specific telomerase recognition and doxorubicin release in cancer cells.

Analyst 2020 Mar 3;145(6):2152-2158. Epub 2020 Mar 3.

College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan 250014, China.

A Y-type-DNA-functionalized nanogold probe was synthesized to identify telomerase and trigger drug release in cancer cells. This system involved a DNA-functionalized nanogold probe centered on gold nanoparticles with a dense modification of Y-type DNA molecular beacons on the surface. The Y-type DNA molecular beacons consisted of telomerase primers (TPs), a FAM-labeled single-strand DNA (Mismatch-DNA), and a single-strand DNA of two templates (Linker-DNA1 and Linker-DNA2). Doxorubicin (Dox), an anti-cancer drug molecule, was inserted into DNA double strands. When telomerase existed, TP was extended and the Mismatch-DNA was released, leading to the emission of fluorescent light from FAM while releasing Dox. This probe specifically detected cancer cells and did not affect normal cells. This drug delivery system will reduce the tumour size and cause minimal injury to normal tissues.
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http://dx.doi.org/10.1039/c9an02630dDOI Listing
March 2020

Phenotypic and molecular characterisation of a novel species, sp., isolated from the sputum of a patient with secondary tuberculosis in Hubei of China.

Epidemiol Infect 2020 02 14;148:e49. Epub 2020 Feb 14.

Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

A new fast-growing mycobacterium, designated strain QGD101T, was isolated from the sputum of an 84-year-old man suspected of tuberculosis in Wuhan Medical Treatment Center, Hubei, China. This strain was a gram-staining-negative, aerobic, non-spore-forming and catalase-positive bacterium, which was further identified as the NTM by PNB and TCH tests. The moxifloxacin and levofloxacin exhibited strong suppressing function against QGD101T with MIC values of 0.06 and 0.125 µg/ml after drug susceptibility testing of six main antimicrobial agents on mycobacteria. Based on the sequence analysis of 16S rRNA, rpoB, hsp65 and 16S-23S rRNA internal transcribed spacer, the strain QGD101T could not be identified to a species level. Mycobacterium moriokaense ATCC43059T that shared the highest 16S rRNA gene sequence similarity (98%) with strain QGD101T was actually different in genomes average nucleotide identity (78.74%). In addition, the major cellular fatty acids of QGD101T were determined as C18:1ω9c, C16:0 and C18:2ω6c. The DNA G + C content was 64.9% measured by high performance liquid chromatography. Therefore, the phenotypic and genotypic characterisation of this strain led us to the conclusion that it represents a novel species of mycobacteria, for which the name Mycobacterium hubeiense sp. nov. (type strain QGD101T = CCTCCAA 2017003T = KCTC39927T) was proposed. Thus, the results of this study are very significant for the clinical diagnosis of tuberculosis and future personalised medicine.
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http://dx.doi.org/10.1017/S0950268820000436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078510PMC
February 2020

Interpretation of mitochondrial tRNA variants.

Genet Med 2020 05 22;22(5):917-926. Epub 2020 Jan 22.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Purpose: To develop criteria to interpret mitochondrial transfer RNA (mt-tRNA) variants based on unique characteristics of mitochondrial genetics and conserved structural/functional properties of tRNA.

Methods: We developed rules on a set of established pathogenic/benign variants by examining heteroplasmy correlations with phenotype, tissue distribution, family members, and among unrelated families from published literature. We validated these deduced rules using our new cases and applied them to classify novel variants.

Results: Evaluation of previously reported pathogenic variants found that 80.6% had sufficient evidence to support phenotypic correlation with heteroplasmy levels among and within families. The remaining variants were downgraded due to the lack of similar evidence. Application of the verified criteria resulted in rescoring 80.8% of reported variants of uncertain significance (VUS) to benign and likely benign. Among 97 novel variants, none met pathogenic criteria. A large proportion of novel variants (84.5%) remained as VUS, while only 10.3% were likely pathogenic. Detection of these novel variants in additional individuals would facilitate their classification.

Conclusion: Proper interpretation of mt-tRNA variants is crucial for accurate clinical diagnosis and genetic counseling. Correlations with tissue distribution, heteroplasmy levels, predicted perturbations to tRNA structure, and phenotypes provide important evidence for determining the clinical significance of mt-tRNA variants.
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http://dx.doi.org/10.1038/s41436-019-0746-0DOI Listing
May 2020

Genome-wide analysis and characterization of F-box gene family in Gossypium hirsutum L.

BMC Genomics 2019 Dec 19;20(1):993. Epub 2019 Dec 19.

State Key Laboratory of Cotton Biology, Institute of Plant Stress Biology, School of Life Sciences, Henan University, Jinming Street, Kaifeng, 475004, China.

Background: F-box proteins are substrate-recognition components of the Skp1-Rbx1-Cul1-F-box protein (SCF) ubiquitin ligases. By selectively targeting the key regulatory proteins or enzymes for ubiquitination and 26S proteasome mediated degradation, F-box proteins play diverse roles in plant growth/development and in the responses of plants to both environmental and endogenous signals. Studies of F-box proteins from the model plant Arabidopsis and from many additional plant species have demonstrated that they belong to a super gene family, and function across almost all aspects of the plant life cycle. However, systematic exploration of F-box family genes in the important fiber crop cotton (Gossypium hirsutum) has not been previously performed. The genome-wide analysis of the cotton F-box gene family is now possible thanks to the completion of several cotton genome sequencing projects.

Results: In current study, we first conducted a genome-wide investigation of cotton F-box family genes by reference to the published F-box protein sequences from other plant species. 592 F-box protein encoding genes were identified in the Gossypium hirsutume acc.TM-1 genome and, subsequently, we were able to present their gene structures, chromosomal locations, syntenic relationships with their parent species. In addition, duplication modes analysis showed that cotton F-box genes were distributed to 26 chromosomes, with the maximum number of genes being detected on chromosome 5. Although the WGD (whole-genome duplication) mode seems play a dominant role during cotton F-box gene expansion process, other duplication modes including TD (tandem duplication), PD (proximal duplication), and TRD (transposed duplication) also contribute significantly to the evolutionary expansion of cotton F-box genes. Collectively, these bioinformatic analysis suggest possible evolutionary forces underlying F-box gene diversification. Additionally, we also conducted analyses of gene ontology, and expression profiles in silico, allowing identification of F-box gene members potentially involved in hormone signal transduction.

Conclusion: The results of this study provide first insights into the Gossypium hirsutum F-box gene family, which lays the foundation for future studies of functionality, particularly those involving F-box protein family members that play a role in hormone signal transduction.
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http://dx.doi.org/10.1186/s12864-019-6280-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921459PMC
December 2019

Comparing effects of berberine on the growth and photosynthetic activities of Microcystis aeruginosa and Chlorella pyrenoidosa.

Water Sci Technol 2019 Sep;80(6):1155-1162

Tianjin Key Laboratory of Aqua-Ecology and Aquaculture, College of Fisheries, Tianjin Agricultural University, Tianjin 300384, China E-mail:

Berberine is a potent algicidal allelochemical of Microcystis aeruginosa. To optimize its application in the control of Microcystis blooms, the effects of berberine on the growth and photosynthetic activities of M. aeruginosa and a non-target green alga, Chlorella pyrenoidosa, were compared. The results showed that the algicidal activity of berberine on M. aeruginosa was light dependent. Berberine had no algicidal effects on C. pyrenoidosa with or without light exposure. Under light-dark conditions, berberine significantly decreased the chlorophyll fluorescence parameters in M. aeruginosa while no significant berberine-induced changes were observed under constant darkness. Significant reductions of photosystem II (PSII) and whole chain electron transport activities in M. aeruginosa exposed to berberine suggested that PSII was the important target site attacked by berberine. Contrary to M. aeruginosa, no berberine-induced inhibition in photosynthesis activities were observed in C. pyrenoidosa. The differences in photosynthetic apparatuses of these two algae might be responsible for their different sensitivities to berberine.
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http://dx.doi.org/10.2166/wst.2019.357DOI Listing
September 2019

Genotyping-by-Sequencing of Races and Cultivars Uncovers Novel Patterns of Genetic Relationships and Domestication Footprints.

Evol Bioinform Online 2019 20;15:1176934319889948. Epub 2019 Nov 20.

Institute of Plant Stress Biology, State Key Laboratory of Cotton Biology, Henan University, Kaifeng, China.

Determining the genetic rearrangement and domestication footprints in cultivars and primitive race genotypes are essential for effective gene conservation efforts and the development of advanced breeding molecular markers for marker-assisted breeding. In this study, 94 accessions representing the 7 primitive races of , along with 9 and 12 cultivated accessions were evaluated. The genotyping-by-sequencing (GBS) approach was employed and 146 558 single nucleotide polymorphisms (SNP) were generated. Distinct SNP signatures were identified through the combination of selection scans and association analyses. Phylogenetic analyses were also conducted, and we concluded that the Latifolium, Richmondi, and Marie-Galante race accessions were more genetically related to the cultivars and tend to cluster together. Fifty-four outlier SNP loci were identified by selection-scan analysis, and 3 SNPs were located in genes related to the processes of plant responding to stress conditions and confirmed through further genome-wide signals of marker-phenotype association analysis, which indicate a clear selection signature for such trait. These results identified useful candidate gene locus for cotton breeding programs.
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http://dx.doi.org/10.1177/1176934319889948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868568PMC
November 2019

Diagnostic gene sequencing panels: from design to report-a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Genet Med 2020 03 16;22(3):453-461. Epub 2019 Nov 16.

Department of Pathology, University of Utah, Salt Lake City, UT, USA.

Gene sequencing panels are a powerful diagnostic tool for many clinical presentations associated with genetic disorders. Advances in DNA sequencing technology have made gene panels more economical, flexible, and efficient. Because the genes included on gene panels vary widely between laboratories in gene content (e.g., number, reason for inclusion, evidence level for gene-disease association) and technical completeness (e.g., depth of coverage), standards that address technical and clinical aspects of gene panels are needed. This document serves as a technical standard for laboratories designing, offering, and reporting gene panel testing. Although these principles can apply to multiple indications for genetic testing, the primary focus is on diagnostic gene panels (as opposed to carrier screening or predictive testing) with emphasis on technical considerations for the specific genes being tested. This technical standard specifically addresses the impact of gene panel content on clinical sensitivity, specificity, and validity-in the context of gene evidence for contribution to and strength of evidence for gene-disease association-as well as technical considerations such as sequencing limitations, presence of pseudogenes/gene families, mosaicism, transcript choice, detection of copy-number variants, reporting, and disclosure of assay limitations.
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http://dx.doi.org/10.1038/s41436-019-0666-zDOI Listing
March 2020

Marine Natural Products and Drug Resistance in Latent Tuberculosis.

Mar Drugs 2019 Sep 26;17(10). Epub 2019 Sep 26.

The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Pyrazinamide (PZA) is the only drug for the elimination of latent (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as an anti-TB agent have received much attention, where some compounds extracted from marine sponge, Haliclona sp. exhibited strong activity under aerobic and hypoxic conditions. In this study, we screened articles from 1994 to 2019 related to marine natural products (MNPs) active against latent MTB isolates. The literature was also mined for the major regulators to map them in the form of a pathway under the dormant stage. Five compounds were found to be more suitable that may be applied as an alternative to PZA for the better management of resistance under latent stage. However, the mechanism of actions behind these compounds is largely unknown. Here, we also applied synthetic biology to analyze the major regulatory pathway under latent TB that might be used for the screening of selective inhibitors among marine natural products (MNPs). We identified key regulators of MTB under latent TB through extensive literature mining and mapped them in the form of regulatory pathway, where SigH is negatively regulated by RshA. PknB, RshA, SigH, and RNA polymerase (RNA-pol) are the major regulators involved in MTB survival under latent stage. Further studies are needed to screen MNPs active against the main regulators of dormant MTB isolates. To reduce the PZA resistance burden, understanding the regulatory pathways may help in selective targets of MNPs from marine natural sources.
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http://dx.doi.org/10.3390/md17100549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836121PMC
September 2019

CpG Oligodeoxynucleotide Promotes Apoptosis of Human Bladder Cancer T24 Cells Via Inhibition of the Antiapoptotic Factors.

Technol Cancer Res Treat 2019 01;18:1533033819873636

Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.

Objective: Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotide, a synthetic oligodeoxynucleotide, has been used as an adjuvant in clinic and in the antitumor activity. However, the antitumor mechanism of cytosine-phosphorothioate-guanine oligodeoxynucleotide against human bladder cancer is unknown. The purpose of this study is to evaluate the cytotoxicity and molecular mechanism of anticancer effect of cytosine-phosphorothioate-guanine oligodeoxynucleotide on T24 cells (a human bladder cancer cell line).

Methods: The cytotoxic activity of cytosine-phosphorothioate-guanine oligodeoxynucleotide was examined by cell viability assay in the presence and absence of 5-fluorouracil, respectively. Apoptosis and cell-cycle phase distribution were detected by flow cytometry analysis. To investigate the molecular mechanisms of cytosine-phosphorothioate-guanine oligodeoxynucleotide cytotoxicity, the expression of antiapoptotic factors (B-cell lymphoma-2 and Survivin, β-actin as control) in RNA, and protein level was assayed by quantitative real-time polymerase chain reaction and automated capillary Western blot.

Results: The inhibition ratio of T24 cells treated with both cytosine-phosphorothioate-guanine oligodeoxynucleotide and 5-fluorouracil was higher than those treated with either cytosine-phosphorothioate-guanine oligodeoxynucleotide or 5-fluorouracil alone. In the combination group (cytosine-phosphorothioate-guanine oligodeoxynucleotide and 5-fluorouracil), the apoptosis rate was significantly increased, and more cells were arrested at "S" and "G2/M" phases compared to those in cytosine-phosphorothioate-guanine oligodeoxynucleotide or 5-fluorouracil alone. Furthermore, the expression of antiapoptotic factors was decreased by cytosine-phosphorothioate-guanine oligodeoxynucleotide alone or combined with 5-fluorouracil.

Conclusion: Cytosine-phosphorothioate-guanine oligodeoxynucleotide promoted apoptosis and enhanced the chemosensitivity of 5-fluorouracil in T24 cells. Cytosine-phosphorothioate-guanine oligodeoxynucleotide downregulated the expression of antiapoptotic factors and inhibited cell-cycle phase by arresting more cells at "S" and "G2/M" phases. This study indicated the potential ability of cytosine-phosphorothioate-guanine oligodeoxynucleotide as a candidate drug for human bladder cancer.
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http://dx.doi.org/10.1177/1533033819873636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759714PMC
January 2019

Karyopherin MoKap119-mediated nuclear import of cyclin-dependent kinase regulator MoCks1 is essential for Magnaporthe oryzae pathogenicity.

Cell Microbiol 2020 01 9;22(1):e13114. Epub 2019 Oct 9.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, China.

Nuclear import of proteins relies on nuclear import receptors called importins/karyopherins (Kaps), whose functions were reported in yeasts, fungi, plants, and animal cells, including cell cycle control, morphogenesis, stress sensing/response, and also fungal pathogenecity. However, limited is known about the physiological function and regulatory mechanism of protein import in the rice-blast fungus Magnaporthe oryzae. Here, we identified an ortholog of β-importin in M. oryzae encoded by an ortholog of KAP119 gene. Functional characterisation of this gene via reverse genetics revealed that it is required for vegetative growth, conidiation, melanin pigmentation, and pathogenicity of M. oryzae. The mokap119Δ mutant was also defective in formation of appressorium-like structure from hyphal tips. By affinity assay and liquid chromatography-tandem mass spectrometry, we identified potential MoKap119-interacting proteins and further verified that MoKap119 interacts with the cyclin-dependent kinase subunit MoCks1 and mediates its nuclear import. Transcriptional profiling indicated that MoKap119 may regulate transcription of infection-related genes via MoCks1 regulation of MoSom1. Overall, our findings provide a novel insight into the regulatory mechanism of M. oryzae pathogenesis likely by MoKap119-mediated nuclear import of the cyclin-dependent kinase subunit MoCks1.
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http://dx.doi.org/10.1111/cmi.13114DOI Listing
January 2020

A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene () causing pyruvate dehydrogenase complex deficiency.

JIMD Rep 2019 Jul 17;48(1):26-35. Epub 2019 Jun 17.

Division of Genetics and Genomics, The Manton Center for Orphan Disease Research Boston Children's Hospital, Harvard Medical School Boston Massachusetts.

Congenital lactic acidosis due to pyruvate dehydrogenase phosphatase (PDP) deficiency is very rare. PDP regulates pyruvate dehydrogenase complex (PDC) and defective PDP leads to PDC deficiency. We report a case with functional PDC deficiency with low activated (+dichloroacetate) and inactivated (+fluoride) PDC activities in lymphocytes and fibroblasts, normal activity of other mitochondrial enzymes in fibroblasts, and novel biallelic frameshift mutation in the gene, c.575dupT (p.L192FfsX5), with absent PDP1 product in fibroblasts. Unexpectedly, the patient also had low branched-chain 2-ketoacid dehydrogenase (BCKDH) activity in fibroblasts with slight elevation of branched-chain amino acids in plasma and ketoacids in urine but with no pathogenic mutations in the enzymes of BCKDH, which could suggest shared regulatory function of PDC and BCKDH in fibroblasts, potentially in other tissues or cell types as well, but this remains to be determined. The clinical presentation of this patient overlaps that of other patients with primary-specific PDC deficiency, with neonatal/infantile and childhood lactic acidosis, normal lactate to pyruvate ratio, elevated plasma alanine, delayed psychomotor development, epileptic encephalopathy, feeding difficulties, and hypotonia. This patient exhibited marked improvement of overall development following initiation of ketogenic diet at 31 months of age. To the best of our knowledge, this is the fourth case of functional PDC deficiency with a defined mutation in .

Synopsis: Pyruvate dehydrogenase phosphatase (PDP) regulates pyruvate dehydrogenase complex (PDC) and defective PDP due to mutations leads to PDC deficiency and congenital lactic acidosis.
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http://dx.doi.org/10.1002/jmd2.12054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606986PMC
July 2019

Microcystins distribution, bioaccumulation, and Microcystis genotype succession in a fish culture pond.

Sci Total Environ 2019 Oct 12;688:380-388. Epub 2019 Jun 12.

Department of Molecular Sciences, PO Box 7015, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden. Electronic address:

In freshwater aquaculture ponds, cyanobacterial blooms and microcystins (MCs) pollution have attracted considerable attention due to their toxic effects. To provide an insight into cyanobacterial problems in aquaculture ponds, MCs distribution, bioaccumulation, and Microcystis genotype succession in a fishpond were investigated from May 2017 to November 2017. The distribution of MCs in filtered water, seston, and sediment varied considerably among months. MCs concentrations in filtered water, seston, and sediment ranged from 1.16 to 3.66 μg/L, 0.64 to 13.98 μg/g DW, and 1.34 to 5.90 μg/g DW, respectively. In addition, chemical oxygen demand was positively correlated with sestonic MCs concentrations. MCs concentrations accumulated in different tissues of market-size fish were in the order of liver > kidney > intestine > muscle. MCs content in muscle was 4.3 times higher than the WHO recommended tolerable daily intake level. Twenty-four ITS genotypes of Microcystis were identified from a total of 653 sequences. During the survey period, considerable genotype variation and rapid genotype succession were observed and dominant genotype was absent. A redundancy analysis revealed that Microcystis genotypes could significantly influence the variations in the proportions of the potentially toxic Microcystis, which could in turn influence the MCs concentrations in seston.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.156DOI Listing
October 2019

Histochemical distribution of four types of enzymes and mucous cells in the intestine of koi carp (Cyprinus carpio var. koi).

Fish Physiol Biochem 2019 Aug 17;45(4):1367-1376. Epub 2019 Jun 17.

Tianjin Key Laboratory of Aqua-Ecology and Aquaculture, Fisheries College, Tianjin Agricultural University, Tianjin, 300384, China.

The main purpose of this study was to investigate the distribution of acid phosphatase (ACP), alkaline phosphatase (ALP), non-specific esterase (NSE), peroxidase (POD), and mucous cells in the intestine of the koi carp Cyprinus carpio var. koi. ACP activity was located in the striated border, enterocytes, and lamina propria of the anterior and middle intestines. The ACP activity in the anterior intestine was higher than that in the middle and posterior intestines. ALP existed in the striated border of enterocytes and lamina propria, serosa, muscular layer, and the junction between muscular layer and submucosa layer of the intestine. The ALP activity in the anterior intestine was higher than that in the middle and posterior intestines. NSE activity was localized in the cytoplasm of enterocytes in the whole intestine, and the middle intestine showed the lower NSE activity than the anterior and posterior intestines. POD activity was localized in the blood cells of the lamina propria and cytoplasm of enterocytes in all intestinal segments. The POD activity among the anterior, middle, and posterior intestines was non-significantly different. Alcian blue periodic acid-Schiff histochemical results revealed three types of mucous cells in the intestine. The total number of mucous cells and percentage of type I cells among the anterior, middle, and posterior intestines were non-significantly different. The percentage of the type II cells was the highest in the posterior intestine, while the lowest in the anterior intestine. The percentage of the type III cells was the highest in the anterior intestine, while the lowest in the posterior intestine.
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http://dx.doi.org/10.1007/s10695-019-00673-yDOI Listing
August 2019