Publications by authors named "Huanhuan Zhao"

70 Publications

Predicting the Risk of Hypertension Based on Several Easy-to-Collect Risk Factors: A Machine Learning Method.

Front Public Health 2021 24;9:619429. Epub 2021 Sep 24.

Institute of Health Management, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Hypertension is a widespread chronic disease. Risk prediction of hypertension is an intervention that contributes to the early prevention and management of hypertension. The implementation of such intervention requires an effective and easy-to-implement hypertension risk prediction model. This study evaluated and compared the performance of four machine learning algorithms on predicting the risk of hypertension based on easy-to-collect risk factors. A dataset of 29,700 samples collected through a physical examination was used for model training and testing. Firstly, we identified easy-to-collect risk factors of hypertension, through univariate logistic regression analysis. Then, based on the selected features, 10-fold cross-validation was utilized to optimize four models, random forest (RF), CatBoost, MLP neural network and logistic regression (LR), to find the best hyper-parameters on the training set. Finally, the performance of models was evaluated by AUC, accuracy, sensitivity and specificity on the test set. The experimental results showed that the RF model outperformed the other three models, and achieved an AUC of 0.92, an accuracy of 0.82, a sensitivity of 0.83 and a specificity of 0.81. In addition, Body Mass Index (BMI), age, family history and waist circumference (WC) are the four primary risk factors of hypertension. These findings reveal that it is feasible to use machine learning algorithms, especially RF, to predict hypertension risk without clinical or genetic data. The technique can provide a non-invasive and economical way for the prevention and management of hypertension in a large population.
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http://dx.doi.org/10.3389/fpubh.2021.619429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497705PMC
September 2021

Dapagliflozin Mediates Plin5/PPARα Signaling Axis to Attenuate Cardiac Hypertrophy.

Front Pharmacol 2021 23;12:730623. Epub 2021 Sep 23.

Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China.

The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism. Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed . The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules. After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. , DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both and experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy. Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.
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http://dx.doi.org/10.3389/fphar.2021.730623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495133PMC
September 2021

The zinc transporter ZIP7 (Slc39a7) controls myocardial reperfusion injury by regulating mitophagy.

Basic Res Cardiol 2021 Sep 28;116(1):54. Epub 2021 Sep 28.

Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.

Whereas elimination of damaged mitochondria by mitophagy is proposed to be cardioprotective, the regulation of mitophagy at reperfusion and the underlying mechanism remain elusive. Since mitochondrial Zn may control mitophagy by regulating mitochondrial membrane potential (MMP), we hypothesized that the zinc transporter ZIP7 that controls Zn levels within mitochondria would contribute to reperfusion injury by regulating mitophagy. Mouse hearts were subjected to ischemia/reperfusion in vivo. Mitophagy was evaluated by detecting mitoLC3II, mito-Keima, and mitoQC. ROS were measured with DHE and mitoB. Infarct size was measured with TTC staining. The cardiac-specific ZIP7 conditional knockout mice (ZIP7 cKO) were generated by adopting the CRISPR/Cas9 system. Human heart samples were obtained from donors and recipients of heart transplant surgeries. KO or cKO of ZIP7 increased mitophagy under physiological conditions. Mitophagy was not activated at the early stage of reperfusion in mouse hearts. ZIP7 is upregulated at reperfusion and ZIP7 cKO enhanced mitophagy upon reperfusion. cKO of ZIP7 led to mitochondrial depolarization by increasing mitochondrial Zn and, accumulation of PINK1 and Parkin in mitochondria, suggesting that the decrease in mitochondrial Zn in response to ZIP7 upregulation resulting in mitochondrial hyperpolarization may impede PINK1 and Parkin accumulation in mitochondria. Notably, ZIP7 is markedly upregulated in cardiac mitochondria from patients with heart failure (HF), whereas mitochondrial PINK1 accumulation and mitophagy were suppressed. Furthermore, ZIP7 cKO reduced mitochondrial ROS generation and myocardial infarction via a PINK1-dependet manner, whereas overexpression of ZIP7 exacerbated myocardial infarction. Our findings identify upregulation of ZIP7 leading to suppression of mitophagy as a critical feature of myocardial reperfusion injury. A timely suppression of cardiac ZIP7 upregulation or inactivation of ZIP7 is essential for the treatment of reperfusion injury.
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http://dx.doi.org/10.1007/s00395-021-00894-4DOI Listing
September 2021

Integrative Analysis of mA Regulator-Mediated RNA Methylation Modification Patterns and Immune Characteristics in Lupus Nephritis.

Front Cell Dev Biol 2021 7;9:724837. Epub 2021 Sep 7.

Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: There is growing evidence to demonstrate that the epigenetic regulation of immune characteristics, especially for N6-methyladenosine (mA) RNA methylation. However, how mA methylation is involved in lupus nephritis (LN) is still unclear. This study aimed to determine the role of mA RNA methylation and their association with the immune microenvironment in LN.

Methods: In total, 87 glomeruli (73 LN, 14 living healthy donors), 110 tubulointerstitium (95 LN, 15 living healthy donors), and 21 kidney whole tissue samples (14 LN, 7 controls) were included in our research to evaluate the expression levels of mA regulators. CIBERSORT was used to assess the abundance of infiltrating immunocytes. The mA regulator gene signature for LN was identified using LASSO-logistic regression and verified with external data. Consensus clustering algorithms were used for the unsupervised cluster analysis of mA modification patterns in LN. Single-sample gene-set enrichment analysis and gene set variation analysis algorithms were employed to assess the activity of immune responses and other functional pathways. Weighted gene co-expression network analysis and protein-protein interaction networks were used to identify mA methylation markers. Lastly, the Nephroseq V5 tool was used to analyze the correlation between mA markers and renal function.

Results: We found that the expression of mA regulators was more significantly different in the glomeruli in LN compared with tubulointerstitium and whole kidney tissue. We established an mA regulator signature, comprised of , , , , , and , that can easily distinguish LN and healthy individuals. Two distinct mA modification patterns based on 18 mA regulators were determined, with significant differences in mA regulator expression, immune microenvironment, biological functional pathways, and clinical characteristics. Activated NK cells, most immune responses, and HLA genes had strong correlations with mA regulators. Seven mA markers were identified and demonstrated a meaningful correlation with GFR, indicating that they are potential prognostic biomarkers.

Conclusion: This study emphasized that mA RNA methylation and the immune microenvironment are closely linked in LN. A better understanding of mA modification patterns provide a basis for the development of novel therapeutic options for LN.
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http://dx.doi.org/10.3389/fcell.2021.724837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454410PMC
September 2021

Six air pollutants and cause-specific mortality: a multi-area study in nine counties or districts of Anhui Province, China.

Environ Sci Pollut Res Int 2021 Jul 31. Epub 2021 Jul 31.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Shushan District, Hefei, 230032, Anhui, China.

Air pollution and its negative effects on health of people have been a global concern. Many studies had found a strong association between air pollutants and risk of death, but few had focused on the effects of six pollutants and rural areas. Our study aimed to investigate the effects of six air pollutants (CO, NO, O, PM, PM, and SO) on non-accidental and respiratory deaths in rural areas of Anhui Province by adjusting for confounding factors, and to further clarify which populations were susceptible to death associated with air pollution. In the first phase of the analysis, the generalized additive models were combined with the distributed lag non-linear models to evaluate the individual effects of air pollution on death in each area. In the second stage, random-effects models were used to aggregate the associations between air pollutants and mortality risk in nine areas. Overall, six pollutants had the strongest effects on the risk of death on the lag 07 days. The associations between PM and NO and daily non-accidental deaths were strongest, with maximum RR (lag 07): 1.63 (1.37-1.88) and 1.67 (1.37-1.96). The maximum pooled effects of association between six air pollutants and RD were PM, with RR (lag 07): 1.89 (1.45-2.34). PM and PM had significant differences between the elderly and the non-elderly with respectively, RRR: 1.22 (1.04-1.41) and 1.26 (1.11-1.42). In general, we found that six air pollutants were the important risk factors for deaths (deaths from respiratory disease and non-accidental) in rural areas of Anhui Province. PM and PM had a considerable impact on the elderly.
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http://dx.doi.org/10.1007/s11356-021-15730-4DOI Listing
July 2021

Fusaricide is a Novel Iron Chelator that Induces Apoptosis through Activating Caspase-3.

J Nat Prod 2021 08 22;84(8):2094-2103. Epub 2021 Jul 22.

State Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.

Nonsmall cell lung cancer (NSCLC) has been a fatal and refractory disease worldwide. Novel therapeutic developments based on fundamental investigations of anticancer mechanisms underlie substantial foundations to win the fight against cancer diseases. In this study, we isolated a natural product fusaricide (FCD) from an endophytic fungus of , identified as . For the first time, we discovered that FCD potently inhibited proliferation in a variety of human NSCLC cell lines, with relatively less toxicity to normal cells. Our study exhibited that FCD induced apoptosis, caused DNA damage and cell cycle arrest in G0/G1 phase, and activated caspase-3 as well as other apoptosis-related factors in human NSCLC NCI-H460 cells. FCD was proven to be an iron chelator that actively decreased levels of cellular labile iron pool in NCI-H460 cells in our study. FeCl supplement reversed FCD-induced apoptosis. The upregulation of transferrin receptor 1 (TfR1) and downregulation of ferritin heavy chain (FTH) expression were observed after FCD treatment. In summary, our study highlighted the potential anticancer effects of FCD against human NSCLCs and demonstrated that the FCD-mediated apoptosis depended on binding to intracellular iron.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01322DOI Listing
August 2021

Morphine Prevents Ischemia/Reperfusion-Induced Myocardial Mitochondrial Damage by Activating δ-opioid Receptor/EGFR/ROS Pathway.

Cardiovasc Drugs Ther 2021 Jul 19. Epub 2021 Jul 19.

School of Public Health, North China University of Science and Technology, 21 Bohai Avenue, Caofeidian District, Tangshan, 063000, Hebei, China.

Objective: The purpose of this study was to determine whether the epidermal growth factor receptor (EGFR), which is a classical receptor tyrosine kinase, is involved in the protective effect of morphine against ischemia/reperfusion (I/R)-induced myocardial mitochondrial damage.

Methods: Isolated rats hearts were subjected to global ischemia followed by reperfusion. Cardiac H9c2 cells were exposed to a simulated ischemia solution followed by Tyrode's solution to induce hypoxia/reoxygenation (H/R) injury. Triphenyltetrazolium chloride (TTC) was used to measure infarct size. The mitochondrial morphological and functional changes were determined using transmission election microscopy (TEM), mitochondrial stress assay, and mitochondrial swelling, respectively. Mitochondrial fluorescence indicator JC-1, DCFH-DA, and Mitosox Red were used to determine mitochondrial membrane potential (△Ψm), intracellular reactive oxygen species (ROS) and mitochondrial superoxide. A TUNUL assay kit was used to detect the level of apoptosis. Western blotting analysis was used to measure the expression of proteins.

Results: Treatment of isolated rat hearts with morphine prevented I/R-induced myocardial mitochondrial injury, which was inhibited by the selective EGFR inhibitor AG1478, suggesting that EGFR is involved in the mitochondrial protective effect of morphine under I/R conditions. In support of this hypothesis, the selective EGFR agonist epidermal growth factor (EGF) reduced mitochondrial morphological and functional damage similarly to morphine. Further study demonstrated that morphine may alleviate I/R-induced cardiac damage by inhibiting autophagy but not apoptosis. Morphine increased protein kinase B (Akt), extracellular regulated protein kinases (ERK) and signal transducer and activator of transcription-3 (STAT-3) phosphorylation, which was inhibited by AG1478, and EGF had similar effects, indicating that morphine may activate Akt, ERK, and STAT-3 via EGFR. Morphine and EGF increased intracellular reactive oxygen species (ROS) generation. This effect of morphine was inhibited by AG1478, indicating that morphine promotes intracellular ROS generation by activating EGFR. However, morphine did not increase ROS generation when cells were transfected with siRNA against EGFR. In addition, EGFR activity was markedly increased by morphine, but the effect of morphine was reversed by naltrindole. These results suggest that morphine may activate EGFR via δ-opioid receptor activation.

Conclusions: Morphine may prevent I/R-induced myocardial mitochondrial damage by activating EGFR through δ-opioid receptors, in turn increasing RISK and SAFE pathway activity via intracellular ROS. Moreover, morphine may reduce myocardial injury by regulating autophagy but not apoptosis.
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http://dx.doi.org/10.1007/s10557-021-07215-wDOI Listing
July 2021

Research on enterprise business model and technology innovation based on artificial intelligence.

EURASIP J Wirel Commun Netw 2021 3;2021(1):145. Epub 2021 Jul 3.

College of Management, Wuxi Institute of Technology, Wuxi, 214121 China.

Small- and medium-sized enterprises (SEMs) are the important part of economic society whose innovation activities are of great significance for building innovative country. In order to investigate how technological innovation (TI) and business model design (BMD) affect the business performance of SMEs, samples of 268 SMEs in the artificial intelligence industry and hierarchical regression models are used in the analysis. The results indicate that TI, BMD, and the matching of them have different effects on the innovation of SMEs of different sizes. These findings are helpful for enriching the theory of the fit between TI and BMD and providing theoretical guidance for the innovation activities in SEMs.
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http://dx.doi.org/10.1186/s13638-021-02025-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254430PMC
July 2021

Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway.

J Exp Clin Cancer Res 2021 Jun 21;40(1):199. Epub 2021 Jun 21.

Department of Physiology and Pathophysiology, Tianjin Medical University, 300070, Tianjin, China.

Background: Zinc transporters have been found to be associated with the pathogenesis of numerous human diseases including cancer. As the most lethal gynecologic malignancy, ovarian cancer is characterized by rapid progression and widespread metastases. However, the function and underlying mechanism of zinc transporters in ovarian cancer metastasis remain unclear.

Methods: The relationship between zinc transporter gene expressions and clinical outcomes of ovarian cancer was assessed with the online database Kaplan-Meier plotter ( http://kmplot.com/analysis/ ). Immunohistochemistry was performed to investigate the prognostic importance of ZIP13. The expression of ZIP13 in ovarian cancer cell lines was depleted to explore its effect on proliferation, adhesion, migration, and invasion both in vitro and in vivo assays. RNA-Seq, quantitative RT-PCR, and western blot analysis were performed to explore ZIP13-regulated downstream target genes.

Results: The expressions of several zinc transporters were highly associated the clinical outcomes of ovarian cancer patients. Among them, high ZIP13 expression was an independent prognostic factor for poor survival in patients with ovarian cancer. ZIP13 knockout suppressed the malignant phenotypes of ovarian cancer cells both in vitro and in vivo. Further investigation revealed that ZIP13 regulated intracellular zinc distribution and then affected the expressions of genes involved in extracellular matrix organization and cytokine-mediated signaling pathway. This led to the activation of Src/FAK pathway with increased expressions of pro-metastatic genes but decreased expressions of tumor suppressor genes.

Conclusions: ZIP13 is shown to be a novel driver of metastatic progression by modulating the Src/FAK signaling pathway, which may serve as a promising biomarker for prognostic evaluation and targeted therapy in ovarian cancer.
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http://dx.doi.org/10.1186/s13046-021-01999-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215834PMC
June 2021

Anti-Tumor Effects of in Acute Myeloid Leukemia.

Front Oncol 2021 4;11:694594. Epub 2021 Jun 4.

Department of Pharmacology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Dysregulation of ketone metabolism has been reported in various types of cancer. In order to find out its role in acute myeloid leukemia (AML) pathogenesis, we first analyzed the expression levels of 10 key genes involved in ketone metabolism in AML blasts and CD34 hematopoietic stem cells (HSCs) from healthy donors. We found that the expression level of was significantly lower in AML than in normal HSCs. The downregulation of gene expression in AML cell lines as compared with normal HSCs was further confirmed with real-time RT-PCR. Analysis of TCGA and other database revealed that the downregulation of was associated with worse prognosis in AML patients. In addition, we showed that overexpression of inhibited the viability and proliferation of AML cells. In contrast, knock-down promoted AML cell growth. Collectively, our results suggest the previously unappreciated anti-tumor role of in AML, and low expression predicts poor survival.
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http://dx.doi.org/10.3389/fonc.2021.694594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213090PMC
June 2021

Diabetes Mellitus as a Risk Factor for Progression from Acute Kidney Injury to Acute Kidney Disease: A Specific Prediction Model.

Diabetes Metab Syndr Obes 2021 25;14:2367-2379. Epub 2021 May 25.

Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.

Purpose: Acute kidney injury is very common in hospitalized patients and carries a significant risk of mortality. Although timely intervention may improve patient prognosis, studies on the development of acute kidney disease in patients with acute kidney injury remain scarce. Thus, we constructed a prediction model to identify patients likely to develop acute kidney disease.

Patients And Methods: Among 474 patients screened for eligibility, 261 were enrolled and randomly divided into training (185 patients) and independent validation cohorts (76 patients). Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were used to select features and build a nomogram incorporating the selected predictors: diabetes, anemia, oliguria, and peak creatinine. Calibration, discrimination, and the clinical usefulness of the model were assessed using calibration plots, the C-index, receiver operating characteristic curves, and decision curve analysis.

Results: Diabetes was significantly associated with the presence of AKD. Peak creatinine, oliguria, and anemia also contributed to the progression of acute kidney injury. The model displayed good predictive power with a C-index of 0.834 and an AUC of 0.834 (95% confidence interval (CI): 0.773-0.895) in the training cohort and a C-index of 0.851 and an AUC of 0.851 (95% CI: 0.753-0.949) in the validation cohort. The calibration curves also showed that the model had a medium ability to predict acute kidney disease risk. Decision curve analysis showed that the nomogram was clinically useful when interventions were decided at the possibility threshold of 22%.

Conclusion: This novel prediction nomogram may allow for convenient prediction of acute kidney disease in patients with acute kidney injury, which may help to improve outcomes.
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http://dx.doi.org/10.2147/DMSO.S307776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164678PMC
May 2021

FERONIA receptor kinase-regulated reactive oxygen species mediate self-incompatibility in Brassica rapa.

Curr Biol 2021 Jul 19;31(14):3004-3016.e4. Epub 2021 May 19.

State Key Laboratory of Crop Biology, Shandong Agricultural University, Tai'an, 271018 Shandong, China; College of Horticulture Science and Engineering, Shandong Agricultural University, Tai'an, 271018 Shandong, China. Electronic address:

Most plants in the Brassicaceae evolve self-incompatibility (SI) to avoid inbreeding and generate hybrid vigor. Self-pollen is recognized by the S-haplotype-specific interaction of the pollen ligand S-locus protein 11 (SP11) (also known as S-locus cysteine-rich protein [SCR]) and its stigma-specific S-locus receptor kinase (SRK). However, mechanistically much remains unknown about the signaling events that culminate in self-pollen rejection. Here, we show that self-pollen triggers high levels of reactive oxygen species (ROS) in stigma papilla cells to mediate SI in heading Chinese cabbage (Brassica rapa L. ssp. pekinensis). We found that stigmatic ROS increased after self-pollination but decreased after compatible(CP)- pollination. Reducing stigmatic ROS by scavengers or suppressing the expression of respiratory burst oxidase homologs (Rbohs), which encode plant NADPH oxidases that produce ROS, both broke down SI. On the other hand, increasing the level of ROS inhibited the germination and penetration of compatible pollen on the stigma, mimicking an incompatible response. Furthermore, suppressing a B. rapa FERONIA (FER) receptor kinase homolog or Rac/Rop guanosine triphosphatase (GTPase) signaling effectively reduced stigmatic ROS and interfered with SI. Our results suggest that FER-Rac/Rop signaling-regulated, NADPH oxidase-produced ROS is an essential SI response leading to self-pollen rejection.
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http://dx.doi.org/10.1016/j.cub.2021.04.060DOI Listing
July 2021

Effective Enrichment Strategy Using Boronic Acid-Functionalized Mesoporous Graphene-Silica Composites for Intact N- and O-Linked Glycopeptide Analysis in Human Serum.

Anal Chem 2021 05 20;93(17):6682-6691. Epub 2021 Apr 20.

The Fifth People's Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

The heterogeneity and low abundance of protein glycosylation present challenging barriers to the analysis of intact glycopeptides, which is key to comprehensively understanding the role of glycosylation in an organism. Efficient and specific enrichment of intact glycopeptides could help greatly with this problem. Here, we propose a new enrichment strategy using a boronic acid (BA)-functionalized mesoporous graphene-silica composite (denoted as [email protected]) for isolating intact glycopeptides from complex biological samples. The merits of this composite, including high surface area and synergistic effect from size exclusion functionality of mesoporous material, hydrophilic interaction of silica, and the reversible covalent binding with BA, enable the effective and specific enrichment of both intact N- and O-glycopeptides. The results from the enrichment performance of the strategy evaluated by standard glycoproteins and the application to global N- and O-glycosylation analyses in human serum indicate the robustness and potential of the strategy for intact glycopeptide analysis.
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http://dx.doi.org/10.1021/acs.analchem.0c05482DOI Listing
May 2021

Protein Nanoparticle-Related Osmotic Pressure Modifies Nonselective Permeability of the Blood-Brain Barrier by Increasing Membrane Fluidity.

Int J Nanomedicine 2021 1;16:1663-1680. Epub 2021 Mar 1.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People's Republic of China.

Background: Intracellular tension plays a crucial role in the destruction of the blood-brain barrier (BBB) in response to lesion stimuli. Tight junction structure could be primarily affected by tension activity. In this study, we aimed to determine the effects of extracellular BBB damage on intracellular tension activity, and elucidate the mechanism underlying the effects of intracellular protein nanoparticle-related osmotic pressure on BBB permeability.

Methods: The intracellular tension for tight junction proteins occludin and ZO1 was evaluated using the fluorescence resonance energy transfer (FRET)-based tension probes and cpstFRET analysis. The changes in mobility ratios of occludin were evaluated via the fluorescence recovery after photobleaching (FRAP) test. The cytoplasmic osmotic pressure (OP) was measured using Osmometer. The count rate of cytoplasmic nanoparticles was detected by Nanosight NS300. The activation of cofilin and stathmin was examined by Western blot analysis. The BBB permeability in vivo was determined via the changes of Evans Blue (EB) injected into SD rats. The tight junction formation was assessed by the measurement of transendothelial electrical resistance (TEER). Intracellular calcium or chloride ions were measured using Fluo-4 AM or MQAE dyes.

Results: BBB lesions were accompanied by changes in occludin/ZO1 tension. Increases in intracellular osmotic pressure were involved in alteration of BBB permeability, possibly through the depolymerization of microfilaments or microtubules and mass production of protein nanoparticles according to the Donnan effect. Recovery of protein nanoparticle-related osmotic pressure could effectively reverse the effects of changes in occludin/ZO1 tension under BBB lesions. Outward tension of intracellular osmotic potential also caused upregulation of membrane fluidity, which promoted nonselective drug influx.

Conclusion: Our results suggest a crucial mechanical mechanism underlying BBB lesions, and protein nanoparticle-related osmotic pressure could be a novel therapeutic target for BBB lesion-related brain diseases.
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http://dx.doi.org/10.2147/IJN.S291286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935347PMC
March 2021

[Establishment and verification of risk prediction model of acute exacerbation of chronic obstructive pulmonary disease based on regression analysis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jan;33(1):64-68

Department of Respiratory Diseases, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China.

Objective: To establish a risk prediction model for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) using regression analysis and verify the model.

Methods: The risk factors and acute exacerbation of 1 326 patients with chronic obstructive pulmonary disease (COPD) who entered the stable phase and followed up for 6 months in the four completed multi-center large-sample randomized controlled trials were retrospectively analyzed. Using the conversion-random number generator, about 80% of the 1 326 cases were randomly selected as the model group (n = 1 074), and about 20% were the verification group (n = 252). The data from the model group were selected, and Logistic regression analysis was used to screen independent risk factors for AECOPD, and an AECOPD risk prediction model was established; the model group and validation group data were substituted into the model, respectively, and the receiver operating characteristic (ROC) curve was drawn to verify the effectiveness of the risk prediction model in predicting AECOPD.

Results: There were no statistically significant differences in general information (gender, smoking status, comorbidities, education level, etc.), body mass index (BMI) classification, lung function [forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), etc.], disease status (the number and duration of acute exacerbation in the past year, duration of disease, etc.), quality of life scale [COPD assessment test (CAT), etc.] and clinical symptoms (cough, chest tightness, etc.) between the model group and the validation group. It showed that the two sets of data had good homogeneity, and the cases in the validation group could be used to verify the effectiveness of the risk prediction model established through the model group data to predict AECOPD. Logistic regression analysis showed that gender [odds ratio (OR) = 1.679, 95% confidence interval (95%CI) was 1.221-2.308, P = 0.001], BMI classification (OR = 0.576, 95%CI was 0.331-1.000, P = 0.050), FEV1 (OR = 0.551, 95%CI was 0.352-0.863, P = 0.009), number of acute exacerbation (OR = 1.344, 95%CI was 1.245-1.451, P = 0.000) and duration of acute exacerbation (OR = 1.018, 95%CI was 1.002-1.034, P = 0.024) were independent risk factors for AECOPD. A risk prediction model for AECOPD was constructed based on the results of regression analysis: probability of acute exacerbation (P) = 1/(1+e), x = -3.274+0.518×gender-0.552×BMI classification+0.296×number of acute exacerbation+0.018×duration of acute exacerbation-0.596×FEV1. The ROC curve analysis verified that the area under ROC curve (AUC) of the model group was 0.740, the AUC of the verification group was 0.688; the maximum Youden index of the model was 0.371, the corresponding best cut-off value of prediction probability was 0.197, the sensitivity was 80.1%, and the specificity was 57.0%.

Conclusions: The AECOPD risk prediction model based on the regression analysis method had a moderate predictive power for the acute exacerbation risk of COPD patients, and could assist clinical diagnosis and treatment decision in a certain degree.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200720-00534DOI Listing
January 2021

Knowledge and current practices of ICU nurses regarding aerosol therapy for patients treated with invasive mechanical ventilation: A nationwide cross-sectional study.

J Clin Nurs 2021 Jan 13. Epub 2021 Jan 13.

Department of Medical Records, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Aims And Objectives: This study aimed to determine the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation in China.

Background: Aerosol therapy is a routine operation for intensive care unit (ICU) nurses; however, evidence of the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation is insufficient in China.

Design: A total of 433 hospitals in 92 cities (including 31 capital cities) in 31 provinces in China participated in the study.

Methods: A questionnaire was used to investigate the knowledge and current practices of ICU nurses regarding aerosol therapy for patients treated with invasive mechanical ventilation, including 42 questions covering five aspects: sociodemographic information, aerosolisation devices, atomised drugs, atomisation operation and atomisation-related knowledge. Descriptive analyses of the distribution of the sample are reported as percentages and medians. Univariate and multivariate analysis was used to detect the factors of the interviewee's atomisation knowledge and practices scores. A STROBE checklist was used to guide the reporting of the research.

Results: Of the 1995 questionnaires that were returned, 1978 were analysed. Bronchodilators and glucocorticoids were the most frequently administered drugs. Seventy-four per cent of the total respondents reported placing a filter on the expiratory limb during aerosol therapy, and 47% of these reported that the filter was changed once a day. Only 13% of the respondents reported always turning the heating humidifier off during aerosol therapy, and 48% never did. Knowledge about the optimal droplet size or atomisation yield was poor. Work experience in the ICU and frequency of atomisation training were the independent influencing factors for atomisation knowledge and practice scores (F = 279.653, p < .001; F = 120.556, p < .001, respectively).

Conclusions: The knowledge of ICU nurses about the optimal implementation of aerosol therapy is poor, and the current scientific knowledge about optimal implementation seemed to be applied infrequently. Atomisation-related training should be strengthened, especially for nurses with junior titles and with less work experience.

Relevance To Clinical Practice: Improving the level of ICU nurses' atomisation practice ability is helpful to ensure patient safety. In clinical work, atomisation expert consensus can be used to carry out relevant training and standardise atomisation operation.
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http://dx.doi.org/10.1111/jocn.15639DOI Listing
January 2021

Rapid Sample Preparation Workflow for Serum Sample Analysis with Different Mass Spectrometry Acquisition Strategies.

Anal Chem 2021 01 29;93(3):1578-1585. Epub 2020 Dec 29.

The Fifth People Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China.

Fast, robust, and high-throughput mass spectrometry-based serum proteomic pipelines have great potential to yield information for biomarker discovery and daily clinical practice. Here, we developed a simple and rapid sample preparation (RSP) workflow by reducing the classical pretreatment time from overnight to less than 1.5 h in an ordinary system. In HeLa cell lysates and serum samples, the number of proteins and tryptic peptides generated using the RSP was comparable to that generated using conventional methods. For fast scanning of the serum proteome, the RSP-supported pipeline could complete a test in less than 2 h with 30 min of LC-MS/MS analysis. Nearly 390 proteins spanning 8 magnitudes of abundance range were identified with high reproducibility, containing over 90 cancer-associated proteins and over 50 FDA-approved biomarkers. For fast assay development, eight candidate biomarker peptides for cardiovascular disease (CVD) were quantified by MRM with high accuracy (CV% <10). After a simple highly abundant protein removal, a deep serum proteome of over 1400 proteins was reached. By analyzing the depleted serum in DIA acquisition mode, over 700 proteins were quantified. The differentially expressed proteins could help us unambiguously distinguish the serum samples from healthy people and patients with pancreatic cancer (PC). Potential biomarkers for PC were also found. The new RSP method, which is rapid and simple, meets the demands of both deep mining and fast analysis of serum proteins. We believe that it will be widely used in serum protein studies and accelerate the transformation from biomarker discovery to clinical application.
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http://dx.doi.org/10.1021/acs.analchem.0c03985DOI Listing
January 2021

Metastereotypes impairing doctor-patient relations: The roles of intergroup anxiety and patient trust.

Psych J 2021 Apr 15;10(2):275-282. Epub 2020 Dec 15.

Department of Psychology, Shanghai Normal University, Shanghai, China.

This study examined whether patients' negative metastereotypes undermine their perception of doctor-patient relations through raising their intergroup anxiety and decreasing their trust level. One hundred twenty-four outpatients from a Chinese hospital participated in this study; they were randomly assigned to either the negative metastereotype activation (NMSA) or the non-NMSA condition according to different instructions. Then, they were asked to complete the Intergroup Anxiety, Patient Trust, and Doctor-Patient Relations Scale. Patients' negative metastereotypes undermined doctor-patient relations through the mediation of intergroup anxiety and patient trust (i.e., the independent mediation effect of intergroup anxiety and patient trust) and the serial mediation effect of intergroup anxiety and patient trust. These findings suggest that future research consider intergroup anxiety and patient trust in developing interventions to improve doctor-patient relations.
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http://dx.doi.org/10.1002/pchj.408DOI Listing
April 2021

Downregulation of the zinc transporter SLC39A13 (ZIP13) is responsible for the activation of CaMKII at reperfusion and leads to myocardial ischemia/reperfusion injury in mouse hearts.

J Mol Cell Cardiol 2021 03 9;152:69-79. Epub 2020 Dec 9.

Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China; Department of Cardiology, General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address:

While Zn dyshomeostasis is known to contribute to ischemia/reperfusion (I/R) injury, the roles of zinc transporters that are responsible for Zn homeostasis in the pathogenesis of I/R injury remain to be addressed. This study reports that ZIP13 (SLC39A13), a zinc transporter, plays a role in myocardial I/R injury by modulating the Ca signaling pathway rather than by regulating Zn transport. ZIP13 is downregulated upon reperfusion in mouse hearts or in H9c2 cells at reoxygenation. Ca but not Zn was responsible for ZIP13 downregulation, implying that ZIP13 may play a role in I/R injury through the Ca signaling pathway. In line with our assumption, knockout of ZIP13 resulted in phosphorylation (Thr) of Ca-calmodulin-dependent protein kinase (CaMKII), indicating that downregulation of ZIP13 leads to CaMKII activation. Further studies showed that the heart-specific knockout of ZIP13 enhanced I/R-induced CaMKII phosphorylation in mouse hearts. In contrast, overexpression of ZIP13 suppressed I/R-induced CaMKII phosphorylation. Moreover, the heart-specific knockout of ZIP13 exacerbated myocardial infarction in mouse hearts subjected to I/R, whereas overexpression of ZIP13 reduced infarct size. In addition, knockout of ZIP13 induced increases of mitochondrial Ca, ROS, mitochondrial swelling, decrease in the mitochondrial respiration control rate (RCR), and dissipation of mitochondrial membrane potential (ΔΨm) in a CaMKII-dependent manner. These data suggest that downregulation of ZIP13 at reperfusion contributes to myocardial I/R injury through activation of CaMKII and the mitochondrial death pathway.
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http://dx.doi.org/10.1016/j.yjmcc.2020.12.002DOI Listing
March 2021

Performance of electro-Fenton process coupling with microbial fuel cell for simultaneous removal of herbicide mesotrione.

Bioresour Technol 2021 Jan 13;319:124244. Epub 2020 Oct 13.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

The aim of this work was to investigate the performance of electro-Fenton process coupling with microbial fuel cell for removal of herbicide mesotrione. After a six months acclimation, the anodic biofilm exhibited stable degradation ability to herbicide mesotrione, and the bioelectricity generated by the anodic biofilm could be utilized to in-situ generate HO in cathode. Under the optimized conditions, the mesotrione removal rates reached 0.83 mg Lh for anodic microbial degradation and 1.39 mg Lh for cathodic Fenton oxidation, respectively. The bacteria possessing functions of compounds degradation (e.g. Petrimonas, Desulfovibrio, and Mycobacterium) and electrons transfer (e.g. Petrimonas, Cloacibacillus, and Azospirillum) were selectively enriched in anodic biofilm. Therefore, with the advantages of pollutant removal by simultaneous microbial degradation and Fenton oxidation, the MFC-Fenton offer a promising and sustainable approach for wastewater treatment and refractory contaminants elimination.
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http://dx.doi.org/10.1016/j.biortech.2020.124244DOI Listing
January 2021

An ultrafast and highly efficient enrichment method for both N-Glycopeptides and N-Glycans by bacterial cellulose.

Anal Chim Acta 2020 Dec 8;1140:60-68. Epub 2020 Oct 8.

Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; The Fifth People's Hospital, Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Fudan University, Shanghai, 200032, China; NHC Key Laboratory of Glycoconjugates Research (Fudan University), Shanghai, 200032, China. Electronic address:

A powerful and fast glycopeptide/glycan enrichment method is critical for the efficiency and throughput of mass spectrometry (MS)-based glycoproteomic and glycomic analyses, especially for large-scale sample analysis. Here, we report an ultrafast and effective method for both intact N-glycopeptide and N-glycan enrichment and apply it to human serum samples. In this method, a natural hydrophilic material, bacterial cellulose (BC), was adopted and fully optimized for enrichment. This method offers the following advantages: (i) The enrichment material has natural hydrophilicity and is low-cost, biocompatible, biodegradable and easily accessible; (ii) the whole enrichment procedure is remarkably simple and fast. It takes only 10 min for intact glycopeptides/glycans to be easily purified from mixtures; (iii) the specificity of this method is over 94% for both glycan and glycopeptide enrichment; and (iv) the outstanding specificity of this technique enables high isolation efficiency for the enrichment of both intact glycopeptides and glycans. A total of 36 N-glycans and 31 N-glycopeptides were identified from human immunoglobulin G (IgG). The glycan and glycopeptide absorption capacity of BC was as high as 333 μg/mg and 250 μg/mg (IgG/BC) respectively. The selectivity for glycan and glycopeptide enrichment reached 1:100 (IgG/bovine serum albumin (BSA), molar ratio) and 1:200 (maltoheptaose (DP7)/BSA, molar ratio), respectively. Furthermore, a total of 159 N-glycans and 523 N-glycopeptides were identified in human serum by using this method. Overall, the BC-based enrichment method we present here provides an ultrafast and highly efficient method for the enrichment of both N-glycopeptides and N-glycans in complex samples and shows great potential in large-scale glycoproteomic and glycomic analyses.
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http://dx.doi.org/10.1016/j.aca.2020.10.006DOI Listing
December 2020

Genomic prediction and genomic heritability of grain yield and its related traits in a safflower genebank collection.

Plant Genome 2021 03 2;14(1):e20064. Epub 2020 Nov 2.

School of Applied Systems Biology, La Trobe University, Bundoora, VIC, 3083, Australia.

Safflower, a minor oilseed crop, is gaining increased attention for food and industrial uses. Safflower genebank collections are an important genetic resource for crop enhancement and future breeding programs. In this study, we investigated the population structure of a safflower collection sourced from the Australian Grain Genebank and assessed the potential of genomic prediction (GP) to evaluate grain yield and related traits using single and multi-site models. Prediction accuracies (PA) of genomic best linear unbiased prediction (GBLUP) from single site models ranged from 0.21 to 0.86 for all traits examined and were consistent with estimated genomic heritability (h ), which varied from low to moderate across traits. We generally observed a low level of genome × environment interactions (g × E). Multi-site g × E GBLUP models only improved PA for accessions with at least some phenotypes in the training set. We observed that relaxing quality filtering parameters for genotype-by-sequencing (GBS), such as missing genotype call rate, did not affect PA but upwardly biased h estimation. Our results indicate that GP is feasible in safflower evaluation and is potentially a cost-effective tool to facilitate fast introgression of desired safflower trait variation from genebank germplasm into breeding lines.
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http://dx.doi.org/10.1002/tpg2.20064DOI Listing
March 2021

Influence of urban residents' life satisfaction on prosocial behavioral intentions in the community: A multiple mediation model.

J Community Psychol 2021 03 1;49(2):406-418. Epub 2020 Nov 1.

Department of Psychology, Shanghai Normal University, Shanghai, China.

Prosocial behavior is a category of acts that benefits other people and society. However, previous researchers have paid little attention to the study of community prosocial behavior. Accordingly, the present study adopts multiple mediation analysis to investigate how urban residents' life satisfaction influences their prosocial behavioral intentions in the community. This study collects data from an online survey of Chinese urban residents (N = 765) using self-administered questionnaires. Results show the following: (1) a positive association exists between urban residents' life satisfaction and their community prosocial behavioral intentions; (2) multiple mediation analysis reveals that orientation to meaning life, perception of virtuous humanity, and cognitive reappraisal mediated the relationship between urban residents' life satisfaction and prosocial behavioral intentions. These findings suggest that urban residents' life satisfaction may facilitate their community prosocial behavioral intentions via high levels of orientation to meaning life, perception of virtuous humanity, and cognitive reappraisal. This study also discusses certain contributions and limitations.
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http://dx.doi.org/10.1002/jcop.22467DOI Listing
March 2021

Dark personality traits and cyber aggression in adolescents: A moderated mediation analysis of belief in virtuous humanity and self-control.

Child Youth Serv Rev 2020 Dec 13;119:105565. Epub 2020 Oct 13.

Department of Psychology, Shanghai Normal University, Shanghai, China.

Cyber aggressive behavior among adolescents is a widespread concern. However, little is known about the influencing factors and psychological mechanism of cyber aggressive behavior in adolescents. This study examined whether dark personality traits would be associated with cyber aggression in adolescents, whether belief in virtuous humanity would mediate the relationship between dark personality traits and cyber aggression, and whether self-control would play a moderating role in the links. A total of 675 Chinese college students completed a series of anonymous questionnaires regarding dark personality traits, belief in virtuous humanity, self-control, and cyber aggression. Results showed the following: (1) dark personality was positively related to cyber aggression in adolescents; (2) belief in virtuous humanity mediated the relationship between dark personality traits (i.e., Machiavellianism and psychopathy) and cyber aggression; (3) self-control play a moderating role in the relationship between dark personality traits (i.e., Machiavellianism and psychopathy) and cyber aggression, and the relationship between belief in virtuous humanity and cyber aggression. This study could help demonstrate the risk and protective factors and psychological mechanism of cyber aggressive behavior in adolescents. Some theoretical and practical implications and limitations were also discussed.
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http://dx.doi.org/10.1016/j.childyouth.2020.105565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553069PMC
December 2020

Zinc dysregulation in cancers and its potential as a therapeutic target.

Cancer Biol Med 2020 08;17(3):612-625

Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China.

Zinc is an essential element and serves as a structural or catalytic component in many proteins. Two families of transporters are involved in maintaining cellular zinc homeostasis: the ZIP (SLC39A) family that facilitates zinc influx into the cytoplasm, and the ZnT (SLC30A) family that facilitates zinc efflux from the cytoplasm. Zinc dyshomeostasis caused by the dysfunction of zinc transporters can contribute to the initiation or progression of various cancers, including prostate cancer, breast cancer, and pancreatic cancer. In addition, intracellular zinc fluctuations lead to the disturbance of certain signaling pathways involved in the malignant properties of cancer cells. This review briefly summarizes our current understanding of zinc dyshomeostasis in cancer, and discusses the potential roles of zinc or zinc transporters in cancer therapy.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476080PMC
August 2020

A Novel Risk Model Based on Autophagy Pathway Related Genes for Survival Prediction in Lung Adenocarcinoma.

Med Sci Monit 2020 Sep 2;26:e924710. Epub 2020 Sep 2.

Department of Ophthalmology, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China (mainland).

BACKGROUND Autophagy has a principal role in mediating tumor cell metabolism. However, the role of autophagy-pathway-related genes (APRGs) as prognostic markers remains obscure in lung adenocarcinoma (LUAD). More potential prognostic biomarkers are needed to deepen our understanding to explore the prognostic role of APRGs in LUAD. MATERIAL AND METHODS We used The Cancer Genome Atlas (TCGA) database to identify differentially expressed APRGs. Cox proportional hazard regression was used to identify prognostic APRGs, and then a risk model was constructed. The efficacy of the risk model was confirmed using a testing group. Lastly, we explored mutational signatures of prognostic of APRGs. T-tests were used to analyze all the expression patterns of genes by SPSS 19.0. RESULTS Using TCGA database, 5 differently expressed APRGs were identified in LUAD patients, and functional enrichment analyze of the genes that were closely associated with the survival status in LUAD patients. Cox proportional hazard regression was facilitated to identify 9 APRGs (CCR2, LAMP1, RELA, ATG12, ATG9A, NCKAP1, ATG10, DNAJB9, and MBTPS2). Multivariate Cox proportional hazards regression analyses further identified 5 key prognostic APRGs (CCR2, LAMP1, RELA, ATG12, and MBTPS2) that were closely related to the survival status in LUAD. Then the prognostic scores based on the 5 genes as independent prognostic indicators were constructed for overall survival (OS) of LUAD patients; area under the curve (AUC) values >0.70 (all P<0.05). The efficacy of prognostic scores was confirmed by data from the testing group and showed significant differences between the low-risk and the high-risk groups for OS (P<0.05). CONCLUSIONS The risk model based on the construction of 5 APRGs can predict the prognosis of patients with LUAD, which may potentially predict prognostic signatures for LUAD.
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http://dx.doi.org/10.12659/MSM.924710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486793PMC
September 2020

Effect of anion type on enzymatic hydrolysis of starch-(thermostable α-amylase)-calcium system in a low-moisture solid microenvironment of bioextrusion.

Carbohydr Polym 2020 Jul 22;240:116331. Epub 2020 Apr 22.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, China; National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Fuli Institute of Food Science, Zhejiang University, Hangzhou, 310058, China; Ningbo Research Institute, Zhejiang University, Ningbo 315100, China. Electronic address:

The effect of six anions (Cl-, OH-, NO-, SO-, CHO- and PO-) on a starch (St)-enzyme (thermostable α-amylase, TαA)-calcium (Ca) system was investigated in a low-moisture solid state. Two levels of Ca salts (1 and 10 mmol/100 g St) added to potato starch with and without TαA were analyzed by FT-IR, DSC and SEM. The surface morphologies of the St-Ca complexes were different in the presence of various anions, and the residual Ca salts around the St granules might decrease the enzymatic action. For bioextrusion, TαA (0.5‰ and 1.5‰) were introduced for a relatively low Ca content (1 mmol/100 g). Significant differences in enzyme activity were observed, increasing the activity of TαA by SO- (146.54 %) > CHO- > Cl- > control > NO- > OH- ≈ PO- and CHO- (123.20 %) ≈ Cl- ≈ SO- > control > PO > OH- > NO- for the low and high enzyme levels, respectively.
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http://dx.doi.org/10.1016/j.carbpol.2020.116331DOI Listing
July 2020

Transcriptional regulation of seven cyadox-related genes mainly activated by PI3K and NF-кB signaling pathways in PK-15 cells.

Res Vet Sci 2020 Aug 1;131:232-243. Epub 2020 May 1.

MOA Key Laboratory of Food Safety Evaluation/National Reference Laboratory of Veterinary Drug Residue (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070,PR China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China. Electronic address:

Cyadox, a new antibacterial agent as the quinoxaline-1, 4-dioxides, has a good antibacterial and growth-promoting effect, and has the advantages of lower toxicity, adequate safety and faster absorption. Seven differential expressed genes (DEGs) induced by cyadox were screened in swine liver tissues, including Insulin-like Growth Factor-1 (IGF-1), Epidermal Growth Factor (EGF), Poly ADP-ribose polymerase (PARP), the Defender Against Apoptotic Death 1 (DAD1), Complement Component 3 (C3), Transketolase (TK) and cyadox-related novel gene (CRNG). To elucidate the signal mechanism that cyadox altered these genes expression, the time-effect relationship and signaling pathways related to 7 DEGs induced by cyadox were determined in Porcine Kidney-15 (PK-15) cells by RT-qPCR and the application of various signal pathway inhibitors. The phosphorylation levels of signal factors in PK-15 cells were detected by Western blot. The analyses demonstrated that, the mRNA expressions of 7 DEGs were significantly enhanced by cyadox mainly through the phosphoinositide 3-kinase (PI3K) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) signaling pathways in PK-15 cells. Furthermore, EGF might be the early response gene of cyadox to activate downstream signaling pathways and regulates the expression of other related genes or directly exerting biological effects. In brief, cyadox mainly regulates the expression of these 7 genes by PI3K and NF-кB signaling pathways to exert it's antibacterial and growth-promoting activity in PK-15 cells.
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http://dx.doi.org/10.1016/j.rvsc.2020.04.024DOI Listing
August 2020

Development of a Computational Tool for Automated Interpretation of Intact -Glycopeptide Tandem Mass Spectra from Single Proteins.

Anal Chem 2020 05 21;92(9):6777-6784. Epub 2020 Apr 21.

Precise and automated analysis of site-specific -glycosylation on single proteins is crucial for comprehensive characterization of some important glycoproteins, such as tumor biomarkers and recombinant drug proteins. Mass spectrometry has been proven to be a powerful technique for protein sequencing and -glycosylation analysis. However, challenges remain in developing computational tools for intact -glycopeptide analysis, which has greatly hindered the development of mass-spectrometry-based -glycosylation analysis. Herein, an integrated strategy together with a dedicated automated computational tool termed AOGP was developed for intact -glycopeptide analysis on single proteins. AOGP utilized sequencing for -glycans and a database search strategy for peptide backbones. The false discovery rate (FDR) of the identification results was controlled and validated by a mixed Gaussian distribution estimation method. AOGP exhibited superior performance in identifying intact -glycopeptides of the human erythropoietin with a total of 188 -glycopeptide spectra reported under 1% FDR. AOGP is developed in Python, is fully open-sourced, and is equipped with a user-friendly interface. Such an easy-operating and robust tool would greatly facilitate -glycosylation analysis on single proteins in tumor biomarker and recombinant drug protein development.
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http://dx.doi.org/10.1021/acs.analchem.0c01091DOI Listing
May 2020

Synergistic antibacterial effects of ultrasound and thyme essential oils nanoemulsion against Escherichia coli O157:H7.

Ultrason Sonochem 2020 Sep 25;66:104988. Epub 2020 Jan 25.

College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Integrated Research Base of Southern Fruit and Vegetable Preservation Technology, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou 310058; Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058; Ningbo Research Institute, Zhejiang University, Ningbo 315100. Electronic address:

Essential oil nanoemulsions have been proven to have stronger antimicrobial effects compared to the essential oil alone or coarse emulsion. Sonoporation could be the promising candidate to trigger a synergistic effect with thyme essential oil nanoemulsion (TEON) and produce a more effective antibacterial efficacy. Therefore, in this study, the bactericidal effects of ultrasound (US) in combination with TEON treatments against Escherichia coli (E. coli) O157:H7 were investigated. The remarkable synergistic effects of US (20 kHz, 255 W/cm, 9 min) and TEON (0.375 mg/mL) treatments at 22 °C reduced E. coli O157:H7 populations by 7.42 ± 0.27 log CFU/mL. The morphological changes of cells exposed to different treatments were observed by scanning electron microscopy and transmission electron microscopy. The results showed that the synergistic effects of the ultrasound and TEON treatments altered the morphology and interior microstructure of organism cells. Laser scanning confocal microscopy (LSCM) images revealed that the combination treatments of ultrasound and TEON altered the permeability of cell membranes, and this affected the integrity of E. coli O157:H7 cells. This was further indicated by the high amounts of nucleic acids and proteins released from these cells following treatment. The results from this study illustrated the mechanisms of the synergistic effects of sonoporation and TEON treatments and provided valuable information for their potential in food pasteurization.
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http://dx.doi.org/10.1016/j.ultsonch.2020.104988DOI Listing
September 2020
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