Publications by authors named "Jinglin Zhang"

71 Publications

NOTCH3, a crucial target of miR-491-5p/miR-875-5p, promotes gastric carcinogenesis by upregulating PHLDB2 expression and activating Akt pathway.

Oncogene 2021 Mar 15;40(9):1578-1594. Epub 2021 Jan 15.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, PR China.

Aberrant Notch activation has been implicated in multiple malignancies and the identification of NOTCH receptors and related pathways is critical for targeted therapy. In this study, we aim to delineate the most prominent dysregulated NOTCH receptor and comprehensively reveal its deregulation in gastric cancer (GC). In the four Notch members, NOTCH3 was found uniformly upregulated and associated with poor clinical outcomes in multiple GC datasets. siRNA-mediated NOTCH3 knockdown demonstrated antitumor effects by suppressing cell proliferation, inhibiting monolayer formation, and impairing cell invasion abilities. Its depletion also induced early and late apoptosis. NOTCH3 was confirmed to be a direct target of two tumor suppressor microRNAs (miRNAs), namely miR-491-5p and miR-875-5p. The activation of NOTCH3 is partly due to the silence of these two miRNAs. Through RNA-seq profiling and functional validation, PHLDB2 was identified as a potent functional downstream modulator for NOTCH3 in gastric carcinogenesis. PHLDB2 expression demonstrated a positive correlation with NOTCH3, but was negatively correlated with miR-491-5p. Akt-mTOR was revealed as the downstream signaling of PHLDB2. The NOTCH3-PHLDB2-Akt co-activation was found in 33.7% GC patients and the activation of this axis predicted poor clinical outcome. GC cells treated with siNOTCH3, siPHLDB2, miR-491-5p, miR-875-5p, were more sensitive to Cisplatin and 5-FU. Taken together, the NOTCH3-PHLDB2-Akt cascade plays oncogenic role in gastric carcinogenesis and serves as a therapeutic target. Our study provided insights into Notch-mediated underlying molecular mechanisms and implied translational potential.
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http://dx.doi.org/10.1038/s41388-020-01579-3DOI Listing
March 2021

Myopic retinal changes screening: comparison of sensitivity and specificity among 15 combinations of ultrawide field scanning laser ophthalmoscopy images.

Ophthalmic Res 2021 Jan 5. Epub 2021 Jan 5.

Aims: To investigate the evaluation indices (diagnostic test accuracy and agreement) of 15 combinations of ultrawide field scanning laser ophthalmoscopy (UWF SLO) images in myopic retinal changes (MRC) screening to determine the combination of imaging that yields the highest evaluation indices in screening MRC.

Methods: This is a retrospective study of UWF SLO images obtained from myopes and were analyzed by two retinal specialists independently. 5-field UWF SLO images that included the posterior (B), superior (S), inferior (I), nasal (N) and temporal (T) regions were obtained for analysis and its results used as a reference standard. The evaluation indices of different combinations comprising of one to four fields of the retina were compared to determine the abilities of each combinations screen for MRC.

Results: UWF SLO images obtained from 823 myopic patients (1646 eyes) were included for the study. Sensitivities ranged from 50.0% to 98.9% (95% confidence interval (CI), 43.8-99.7%); the combinations of B+S+I (97.3%; 95% CI, 94.4-98.8%), B+T+S+I (98.5%; 95% CI, 95.9-99.5%), and B+S+N+I (98.9%; 95% CI, 96.4-99.7%) ranked highest. Furthermore, the combinations of B+S+I, B+T+S+I and B+S+N+I also revealed the highest accuracy (97.7%; 95% CI, 95.1-100.0%, 98.6%; 95% CI, 96.7-100.0%, 98.8%; 95% CI, 96.9-100.0%) and agreement (Kappa = 0.968, 0.980 and 0.980). For the various combinations, specificities were all higher than 99.5% (95% CI, 99.3-100.0%).

Conclusion: In our study, screening combinations of B+S+I, B+T+S+I and B+S+N+I stand out with high-performing optimal evaluation indices. However, when time is limited, B+S+I may be more applicable in primary screening of MRC.
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http://dx.doi.org/10.1159/000514176DOI Listing
January 2021

Alkynyl silver modified chitosan and its potential applications in food area.

Carbohydr Polym 2021 Feb 21;254:117416. Epub 2020 Nov 21.

Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, United States. Electronic address:

Chitosan was modified by substituting alkynyl silver on chitosan (Ag-CS) through a two-step chemical modification to form a novel antimicrobial coating material. The physicochemical property, antimicrobial activity, cytotoxicity, and potential food applications of Ag-CS were systematically investigated. The Ag-CS presented a smooth sheet structure, and demonstrated stronger antimicrobial effects than either silver acetate (AgOAc) or silver nitrate (AgNO) against both Gram positive and Gram negative bacteria strains. Ag-CS also demonstrated a controlled release of Ag for over 5 days, whereas AgOAc or AgNO infused chitosan released over 90 % Ag within 4 h. Ag-CS coating on shrimps significantly extended their shelf-life. Overall, our results revealed that the newly developed Ag-CS antimicrobial coating material possesses strong antimicrobial efficacies with a sustained Ag release property, and its ability to slow down the spoilage rate of shrimps indicates its potential in the improvement of food quality and shelf life.
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http://dx.doi.org/10.1016/j.carbpol.2020.117416DOI Listing
February 2021

Analysis of population health projects funded by Joint Fund of the National Natural Science Foundation of China between 2015 and 2019.

Ann Transl Med 2020 Nov;8(22):1477

School of Economics & Management, Communication University of China, Beijing, China.

Background: The National Natural Science Foundation of China (NSFC) is a vital source of support for scientific research in China and abroad. Among the 18 categories programs managed by the NSFC, the Joint Fund, which looks to develop innovation in basic Chinese research, has drawn particular interest from scientists and researchers. This study set out to review the distribution of funding from the Joint Fund in recent years to provide potential applicants with a useful point of reference.

Methods: Guidebooks and annual reports published from 2015 to 2019 were accessed on the NSFC website and the relevant data from the Joint Fund were obtained. The data were analyzed to identify any trends or patterns in funding distribution.

Results: Between 2015 and 2019, the NSFC's Joint Fund awarded a total of 46 million Chinese yuan (CNY) to 354 projects in 29 areas within the field of population health. The funding recipients, who were aged between 30 and 66 years old, came from 47 host institutions. Among the successful applicants, 225 were in senior level positions, 129 were in deputy senior level positions, and 19 were in medium-grade professional positions. Collaboration between institutions was a common feature of funding applications.

Conclusions: By analyzing the distribution of funding from the Joint Fund, we identified a number of common features of successful funding applications, which may help to inform future funding applications.
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http://dx.doi.org/10.21037/atm-20-6495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729363PMC
November 2020

FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential.

Oncogene 2020 10 15;39(43):6647-6663. Epub 2020 Sep 15.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, PR China.

Fibroblast growth factor receptor type 2 (FGFR2) has emerged as a key oncogenic factor that regulates gastric cancer (GC) progression, but the underlying mechanism of FGF-FGFR2 signaling pathway remains largely unknown. To identify the potential molecular mechanisms of the oncogenic FGFR2 in gastric carcinogenesis and convey a novel therapeutic strategy, we profiled the FGFR alterations and analyzed their clinical associations in TCGA and Hong Kong GC cohorts. We found that FGFR2 overexpression in GC cell lines and primary tumors predicted poor survival and was associated with advanced stages of GC. Functionally, growth abilities and cell cycle progression of GC were inhibited by inactivation of ERK-MAPK signal transduction after FGFR2 knockdown, while apoptosis was promoted. Meanwhile, the first-line anti-cancer drug sensitivity was enhanced. RNA-seq analysis further revealed that YAP1 signaling serves as a significant downstream modulator and mediates the oncogenic signaling of FGFR2. When stimulating FGFR2 by rhFGF18, we observed intensified F-actin, nuclear accumulation of YAP1, and overexpression of YAP1 targets, but these effects were attenuated by either FGFR2 depletion or AZD4547 administration. Additionally, the FGF18-FGFR2 signaling upregulated YAP1 expression through activating c-Jun, an effector of MAPK signaling. In our cohort, 28.94% of GC cases were characterized as FGFR2, c-Jun, and YAP1 co-positive and demonstrated worse clinical outcomes. Remarkably, we also found that co-targeting FGFR2 and YAP1 by AZD4547 and Verteporfin synergistically enhanced the antitumor effects in vitro and in vivo. In conclusion, we have identified the oncogenic FGF-FGFR2 regulates YAP1 signaling in GC. The findings also highlight the translational potential of FGFR2-c-Jun-YAP1 axis, which may serve as a prognostic biomarker and therapeutic target for GC.
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http://dx.doi.org/10.1038/s41388-020-01458-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581496PMC
October 2020

MCM family in gastrointestinal cancer and other malignancies: From functional characterization to clinical implication.

Biochim Biophys Acta Rev Cancer 2020 12 19;1874(2):188415. Epub 2020 Aug 19.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, PR China; Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, PR China; Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Centre, The Chinese University of Hong Kong, Hong Kong, SAR, PR China. Electronic address:

Despite the recent advances in cancer research and treatment, gastrointestinal (GI) cancers remain the most common deadly disease worldwide. The aberrant DNA replication serves as a major source of genomic instability and enhances cell proliferation that contributes to tumor initiation and progression. Minichromosome maintenance family (MCMs) is a well-recognized group of proteins responsible for DNA synthesis. Recent studies suggested that dysregulated MCMs lead to tumor initiation, progression, and chemoresistance via modulating cell cycle and DNA replication stress. Their underlying mechanisms in various cancer types have been gradually identified. Furthermore, multiple studies have investigated the association between MCMs expression and clinicopathological features of cancer patients, implying that MCMs might serve as prominent prognostic biomarkers for GI cancers. This review summarizes the current knowledge on the oncogenic role of MCM proteins and highlights their clinical implications in various malignancies, especially in GI cancers. Targeting MCMs might shed light on the potential for identifying novel therapeutic strategies.
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http://dx.doi.org/10.1016/j.bbcan.2020.188415DOI Listing
December 2020

Antifungal Effects of Volatiles Produced by Against in Potato.

Front Microbiol 2020 17;11:1196. Epub 2020 Jun 17.

College of Plant Protection, Hebei Agricultural University, Baoding, China.

Antifungal activities of plant-beneficial have been widely studied in recent years. Numerous studies have studied the antifungal mechanisms of soluble non-volatile bioactive compounds such as lipopeptides and proteins produced by against soil-borne diseases. However, the antagonistic mechanisms of volatile organic compounds (VOCs) from against airborne phytopathogens are still largely unknown, and the function of pathogenic genes has not been well identified. Here, we first isolated a strain with strong antifungal activity and finally identified it as ZD01. Then, the antagonistic mechanisms of VOCs produced by strain ZD01, against , an airborne fungal pathogen that can cause early blight diseases of potato, were studied. We showed that VOCs produced by strain ZD01 can reduce the colony size and mycelial penetration and can cause serious morphological changes of . Scanning electron microscope (SEM) observation showed that VOCs released by ZD01 could cause more flaccid and gapped hyphae of . Also, we found that VOCs produced by ZD01 can inhibit the conidia germination and reduce the lesion areas and number of significantly. Meanwhile, based on gas chromatography/mass spectrometry (GC/MS) analysis, 29 volatile compounds produced by strain ZD01 were identified. Out of 29 identified VOCs, 9 VOCs showed complete growth inhibition activities against . Moreover, we identified two virulence-associated genes ( and ) in . is a key gene that regulates the mycelial growth, penetration, sporulation, and virulence in . In addition, plays a significant role in the SOD synthetic pathway in . Results from qRT-PCR showed that the transcriptional expression of these two genes was down-regulated after being treated by VOCs produced by ZD01. These results are useful for a better understanding of the biocontrol mechanism of and offer a potential method for potato early blight disease control.
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http://dx.doi.org/10.3389/fmicb.2020.01196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311636PMC
June 2020

An Efficient Double-Layer Blockchain Method for Vaccine Production Supervision.

IEEE Trans Nanobioscience 2020 07;19(3):579-587

A vaccine is a biological product which is an important means for human beings to protect themselves. Most of its users are young children with weak immunity. Once a vaccine has a problem, it will pose a serious threat to the lives of many people. At present, the supervision of vaccine production is very simple. The vaccine production record is completely controlled by the enterprises. Enterprises only submit production records to the supervisory agency for review when the vaccine needs to be sold. Production records are easily forged and modified. In order to solve the shortcomings of traditional centralized management. We propose a supervision method for vaccine production based on double-level blockchain. At first, we have designed a double-level blockchain structure. The first level is private data of vaccine prduction enterprise, including production records and corresponding hash. The next level is public data, including production records hash and vaccine information. In this way, we make vaccine enterprise to submit production records in a timely manner without fear of privacy leaks. We avoid enterprise tampering or falsification of production records through the non-tampering features and time stamps of the blockchain. To improve the time efficiency, we propose a consensus mechanism for multi-node cooperate. The primary supervisory node provides sorting services and verifies the correctness of the blockchain replica. The ordinary supervisory node can replace the primary supervisory node when necessary, and help the primary supervisory node recovers data in case of information loss. The review node is responsible for providing complete and correct blockchain copies for other nodes. So we can avoids the problem of waste of time resources in the traditional blockchain system. In addition, in order to avoid the waste of space caused by the redundancy of the blockchain, we propose a vaccine data cutting mechanism. We use the timestamp of the blockchain and the vaccine validity period to determine if the block can be cutted. At the same time, it is also possible to judge whether the block can be cutted based on the information exchange with the vaccination institution. Through these methods, we have realized spatiotemporal efficiency supervision of vaccine production. And for the time being, research work in the field of vaccine production supervision is still very rare. So Our work is ground-breaking.
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http://dx.doi.org/10.1109/TNB.2020.2999637DOI Listing
July 2020

Characterization of key aroma compounds in Huangjiu from northern China by sensory-directed flavor analysis.

Food Res Int 2020 08 19;134:109238. Epub 2020 Apr 19.

Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology & Business University (BTBU), Beijing 100048, China; Beijing Key Laboratory of Flavor Chemistry, Beijing Technology & Business University (BTBU), Beijing 100048, China. Electronic address:

Huangjiu (yellow rice wine) from Shanxi province, with a dominant Zao-aroma (fermented grain aroma), is particularly popular in northern China. The key aroma compounds in Huangjiu from Shanxi province were characterized by sensory-directed flavor analysis. A total of 106 compounds separated with solvent-assisted flavor evaporation (SAFE) distillation were identified by gas chromatography-olfactometry (GC-O) coupled with aroma extract dilution analysis (AEDA) and odor specific magnitude estimation (Osme). Forty-seven of them were further quantitated and 21 odorants had odor activity values (OAVs) ≥ 1. The aroma profiles of three recombination models had >95.84% similarities to their corresponding samples. And then, the omission/addition tests further confirmed that β-phenylethanol, 3-methylbutanoic acid, ethyl lactate, sotolon, 2-acetyl-1-pyrroline, vanillin, ethyl cinnamate, ethyl 3-phenylpropionate, 3-methylbutanal, and methional were the key odorants for Huangjiu from Shanxi province. Meanwhile, it was firstly confirmed that ethyl cinnamate and ethyl 3-phenylpropionate played the key roles in the overall aroma of Huangjiu.
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http://dx.doi.org/10.1016/j.foodres.2020.109238DOI Listing
August 2020

AMOTL1 enhances YAP1 stability and promotes YAP1-driven gastric oncogenesis.

Oncogene 2020 05 20;39(22):4375-4389. Epub 2020 Apr 20.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.

Hippo signaling functions to limit cellular growth, but the aberrant nuclear accumulation of its downstream YAP1 leads to carcinogenesis. YAP1/TEAD complex activates the oncogenic downstream transcription, such as CTGF and c-Myc. How YAP1 is protected in the cytoplasm from ubiquitin-mediated degradation remains elusive. In this study, a member of Angiomotin (Motin) family, AMOTL1 (Angiomotin Like 1), was screened out as the only one to promote YAP1 nuclear accumulation by several clinical cohorts, which was further confirmed by the cellular functional assays. The interaction between YAP1 and AMOTL1 was suggested by co-immunoprecipitation and immunofluorescent staining. The clinical significance of the AMOTL1-YAP1-CTGF axis in gastric cancer (GC) was analyzed by multiple clinical cohorts. Moreover, the therapeutic effect of targeting the oncogenic axis was appraised by drug-sensitivity tests and xenograft-formation assays. The upregulation of AMOTL1 is associated with unfavorable clinical outcomes of GC, and knocking down AMOTL1 impairs its oncogenic properties. The cytoplasmic interaction between AMOTL1 and YAP1 protects each other from ubiquitin-mediated degradation. AMOTL1 promotes YAP1 translocation into the nuclei to activate the downstream expression, such as CTGF. Knocking down AMOTL1, YAP1, and CTGF enhances the therapeutic efficacies of the first-line anticancer drugs. Taken together, AMOTL1 plays an oncogenic role in gastric carcinogenesis through interacting with YAP1 and promoting its nuclear accumulation. A combination of AMOTL1, YAP1, and CTGF expression might serve as a surrogate of Hippo activation status. The co-activation of the AMOTL1/YAP1-CTGF axis is associated with poor clinical outcomes of GC patients, and targeting this oncogenic axis may enhance the chemotherapeutic effects.
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http://dx.doi.org/10.1038/s41388-020-1293-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253359PMC
May 2020

MiR-1246 promotes anti-apoptotic effect of mini-αA in oxidative stress-induced apoptosis in retinal pigment epithelial cells.

Clin Exp Ophthalmol 2020 07 31;48(5):682-688. Epub 2020 Mar 31.

Guangzhou Aier Eye Hospital, Aier Eye Hospital Group, Guangzhou, China.

Background: Geographic atrophy (GA) is a late-stage symptom of an age-related macular degeneration (AMD), characterized by the loss of retinal pigment epithelial (RPE) cells and photoreceptor functions. Despite being a major cause of blindness in individuals of 65 years of age and older, some forms of AMD, including GA, still lack targeted treatment. Our previous study demonstrated that mini-αA peptide, which contains the functional site of αA-crystallin, protected RPE cells from NaIO -induced apoptosis.

Methods: To further investigate the underlying mechanism, we applied next-generation sequencing analysis to identify miR-1246 as a putative mediator of mini-αA protective function. To investigate the role of miR-1246 in RPE cell apoptosis, a stable miR-1246-low-expression cell line was established by using miR-1246 inhibitor. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate the proliferation of RPE cells, mRNA and miR-1246 expression were detected by the quantitative reverse transcriptase-polymerase chain reaction.

Results: We have further identified caspase-3 and caspase-14 as molecular targets of miR-1246 involved in regulation of apoptosis in NaIO -incubated cells. Interestingly, disruption of miR-1246 expression enhanced anti-apoptotic effect of mini-αA on RPE cells during oxidative stress.

Conclusions: Our results provide a mechanistic basis for evaluation of miR-1246 as a new candidate target for the clinical treatment of AMD.
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http://dx.doi.org/10.1111/ceo.13751DOI Listing
July 2020

Gastric cancer: genome damaged by bugs.

Oncogene 2020 04 2;39(17):3427-3442. Epub 2020 Mar 2.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, PR China.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. The role of the microorganisms in gastric tumorigenesis attracts much attention in recent years. These microorganisms include bacteria, virus, and fungi. Among them, Helicobacter pylori (H. pylori) infection is by far the most important risk factor for GC development, with special reference to the early-onset cases. H. pylori targets multiple cellular components by utilizing various virulence factors to modulate the host proliferation, apoptosis, migration, and inflammatory response. Epstein-Barr virus (EBV) serves as another major risk factor in gastric carcinogenesis. The virus protein, EBER noncoding RNA, and EBV miRNAs contribute to the tumorigenesis by modulating host genome methylation and gene expression. In this review, we summarized the related reports about the colonized microorganism in the stomach and discussed their specific roles in gastric tumorigenesis. Meanwhile, we highlighted the therapeutic significance of eradicating the microorganisms in GC treatment.
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http://dx.doi.org/10.1038/s41388-020-1241-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176583PMC
April 2020

Tensor Oriented No-Reference Light Field Image Quality Assessment.

IEEE Trans Image Process 2020 Feb 3. Epub 2020 Feb 3.

Light field image (LFI) quality assessment is becoming more and more important, which helps to better guide the acquisition, processing and application of immersive media. However, due to the inherent high dimensional characteristics of LFI, the LFI quality assessment turns into a multi-dimensional problem that requires consideration of the quality degradation in both spatial and angular dimensions. Therefore, we propose a novel Tensor oriented No-reference Light Field image Quality evaluator (Tensor-NLFQ) based on tensor theory. Specifically, since the LFI is regarded as a low-rank 4D tensor, the principal components of four oriented sub-aperture view stacks are obtained via Tucker decomposition. Then, the Principal Component Spatial Characteristic (PCSC) is designed to measure the spatial-dimensional quality of LFI considering its global naturalness and local frequency properties. Finally, the Tensor Angular Variation Index (TAVI) is proposed to measure angular consistency quality by analyzing the structural similarity distribution between the first principal component and each view in the view stack. Extensive experimental results on four publicly available LFI quality databases demonstrate that the proposed Tensor-NLFQ model outperforms state-of-the-art 2D, 3D, multi-view, and LFI quality assessment algorithms.
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http://dx.doi.org/10.1109/TIP.2020.2969777DOI Listing
February 2020

miR-7 mediates the signaling pathway of NE affecting FSH and LH synthesis in pig pituitary.

J Endocrinol 2020 03;244(3):459-471

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China.

MicroRNA-7 (miR-7) is an important modulator of a plenty of gene expressions and the interrelated biological processes, highly expressed in porcine pituitary. Norepinephrine (NE), acting as an important neurotransmitter or/and a hormone secreted excessively under stress, affects the synthesis and secretion of various hormones, including pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are the key hormones which regulate sexual maturation and reproductive functions. However, the relationship among NE, miR-7 and gonadotropin needs to be elucidated. The aim of this study was to identify whether miR-7 involved in the NE-adrenoceptor signaling pathway affects the synthesis and secretion of FSH and LH in porcine pituitary. Our results showed that the NE intracerebroventricular injection increased pituitary miR-7 level and the synthesis and secretion of FSH and LH in porcine, whereas the inhibition of either endogenous miR-7 or β-adrenergic receptors hindered the rise of FSH and LH synthesis induced by NE in cultured primary porcine anterior pituitary cells. Further, we identified the molecular type of β-adrenergic receptors and the signaling pathway in porcine pituitary, and we found that NE played its roles relying on adrenoceptor beta 2 (β2AR) and the RAF/MEK/ERK1/2 signaling pathway. The phosphorylation of ERK1/2 upregulated miR-7 level which subsequently enhanced FSH and LH synthesis by targeting to Golgi glycoprotein 1 (GLG1). These suggest that miR-7 mediates NE's effect on promoting FSH and LH synthesis in porcine pituitary.
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http://dx.doi.org/10.1530/JOE-19-0331DOI Listing
March 2020

Multi-branch fusion network for Myocardial infarction screening from 12-lead ECG images.

Comput Methods Programs Biomed 2020 Feb 17;184:105286. Epub 2019 Dec 17.

College of Computer Science and Technology, Zhejiang University of Technology, hangzhou, China. Electronic address:

Background And Objective: Myocardial infarction (MI) is a myocardial anoxic incapacitation caused by severe cardiovascular obstruction that can cause irreversible injury or even death. In medical field, the electrocardiogram (ECG) is a common and effective way to diagnose myocardial infarction, which often requires a wealth of medical knowledge. It is necessary to develop an approach that can detect the MI automatically.

Methods: In this paper, we propose a multi-branch fusion framework for automatic MI screening from 12-lead ECG images, which consists of multi-branch network, feature fusion and classification network. First, we use text detection and position alignment to automatically separate twelve leads from ECG images. Then, those 12 leads are input into the multi-branch network constructed by a shallow neural network to get 12 feature maps. After concatenating those feature maps by depth fusion, classification is explored to judge the given ECG is MI or not.

Results: Based on extensive experiments on an ECG image dataset, performances of different combinations of structures are analyzed. The proposed network is compared with other networks and also compared with physicians in the practical use. All the experiments verify that the proposed method is effective for MI screening based on ECG images, which achieves accuracy, sensitivity, specificity and F1-score of 94.73%, 96.41%, 95.94% and 93.79% respectively.

Conclusions: Rather than using the typical one-dimensional electrical ECG signal, this paper gives an effective model to screen MI by analyzing 12-lead ECG images. Extracting and analyzing these 12 leads from their corresponding ECG images is a good attempt in the application of MI screening.
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http://dx.doi.org/10.1016/j.cmpb.2019.105286DOI Listing
February 2020

Targeting the Oncogenic p53 Mutants in Colorectal Cancer and Other Solid Tumors.

Int J Mol Sci 2019 Nov 28;20(23). Epub 2019 Nov 28.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of mutation in tumor development have been comprehensively investigated. In CRC, mutation was associated with poor prognosis and chemoresistance. A gain of function (GOF) of p53 mutants promotes cell proliferation, migration and invasion through multiple mechanisms. Restoring wild type p53 function, depleting p53 mutants, or intervention by targeting the oncogenic downstreams provides potential therapeutic strategies. In this review, we comprehensively summarize the GOF of p53 mutants in CRC progression as well as in some other solid tumors, and discuss the current strategies targeting p53 mutants in malignancies.
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http://dx.doi.org/10.3390/ijms20235999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929124PMC
November 2019

Clinical Outcomes of Transcatheter Aortic Valve Replacement in Nonagenarians: A Systematic Review and Meta-Analysis.

J Interv Cardiol 2019 24;2019:5819232. Epub 2019 Feb 24.

Department of Cardiology, 12th ward, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Beijing 100029, China.

Objectives: To compare the incidence of mortality and complications between nonagenarians and younger patients undergoing transcatheter aortic valve replacement (TAVR).

Background: TAVR has become an alternative treatment for nonagenarian patients with severe aortic stenosis. Previous studies have reported conflicting results regarding the clinical outcomes between nonagenarians and younger patients who underwent TAVR.

Methods: We searched PubMed, EMBASE, and Cochrane Library databases with predefined criteria from the inception dates to July 8, 2018. The primary clinical endpoint was 30-day and 1-year all-cause mortalities. Secondary outcomes were considered the rates of stroke, myocardial infarction, any bleeding, any acute kidney injury, any vascular complications, new pacemaker implantation, and conversion to surgical aortic valve replacement.

Results: A total of 5 eligible studies with 25,371 patients were included in this meta-analysis. Compared with younger patients who underwent TAVR, nonagenarians had a significantly higher mean Society of Thoracic Surgeons score (STS score) (MD, 2.80; 95%CI: 2.58, 3.30; P<0.00001) and logistic European System for Cardiac Operative Risk Evaluation (logistic EuroSCORE) (MD, 2.72; 95%CI: 1.01, 4.43; P=0.002). Nonagenarians were associated with significantly higher 30-day mortality (6.2% vs. 3.7%; OR, 1.73; 95%CI: 1.49, 2.00) and 1-year mortality (15.5% vs. 11.8%; OR, 1.39; 95%CI: 1.26, 1.53), without significant statistical heterogeneity. Nonagenarians were associated with significantly increased rates of major or life-threatening bleeding, vascular complications and stroke of 20%, 35%, and 32%, respectively. There were no significant differences in the rate of myocardial infarction, stage 2 or 3 acute kidney injury, new pacemaker implantation, or conversion to surgical aortic valve replacement.

Conclusions: Nonagenarians showed worse clinical outcomes than younger patients after TAVR, while the incidence of mortality was acceptable. TAVR remains an option for nonagenarian patients with severe aortic stenosis and should be comprehensively evaluated by the heart valve team.
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http://dx.doi.org/10.1155/2019/5819232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739765PMC
February 2020

Ginger essential oil-based microencapsulation as an efficient delivery system for the improvement of Jujube (Ziziphus jujuba Mill.) fruit quality.

Food Chem 2020 Feb 4;306:125628. Epub 2019 Oct 4.

Tianjin Gasin-DH Preservation Technology Co., Ltd, Tianjin 300300, China.

Microencapsulation of Zingiber officinale essential oil (EO) in polysaccharide, chitosan (CH) and sodium carboxymethyl cellulose (CMC) based on the electrostatic interaction between charged polysaccharides at pH 3.0 in dual delivery system. Ratio variations of CH and CMC in microencapsulation were studied at 1:2, 2:1 and 1:1. This study aimed to evaluate the influence of the encapsulating materials combination on freeze-dried EO powders and to present the mechanisms for loading and releasing EO involved in the preparation of CH/CMC microcapsules. The spectroscopy analysis, physical properties, microstructural, encapsulation efficiency and EO release behavior in obtained EO microparticles were evaluated by using the analysis of fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and gas chromatography mass spectrometry (GC-MS), respectively. Afterwards, the above prepared microcapsules were applied on winter jujube fruit (Ziziphus jujuba Mill.) preservation. Results demonstrated that both the microstructure and stability of microencapsulation were improved in delivery system loading with CH and CMC (1:1) with the encapsulation efficiency of 88.50%, compared to other ratios of CH and CMC (1:2 and 2:1). Furthermore, the microencapsulation had a capacity to control and reduce the EO release, therefore the morphological and sensory quality of jujube fruits in EO delivery system during storage was enhanced significantly (P < 0.05), in comparison to control. Results revealed that the microparticles produced with CH and CMC (1:1) was considered to present better characteristics of microstructure, encapsulation efficiency, as well as to maintain higher nutritional quality for jujube fruit. Thus, EO microencapsulation loaded in CH/CMC-based dual delivery system has potential application and developmental value prospects in food industries.
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http://dx.doi.org/10.1016/j.foodchem.2019.125628DOI Listing
February 2020

Targeting the Oncogenic FGF-FGFR Axis in Gastric Carcinogenesis.

Cells 2019 06 25;8(6). Epub 2019 Jun 25.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Gastric cancer (GC) is one of the most wide-spread malignancies in the world. The oncogenic role of signaling of fibroblast growing factors (FGFs) and their receptors (FGFRs) in gastric tumorigenesis has been gradually elucidated by recent studies. The expression pattern and clinical correlations of FGF and FGFR family members have been comprehensively delineated. Among them, FGF18 and FGFR2 demonstrate the most prominent driving role in gastric tumorigenesis with gene amplification or somatic mutations and serve as prognostic biomarkers. FGF-FGFR promotes tumor progression by crosstalking with multiple oncogenic pathways and this provides a rational therapeutic strategy by co-targeting the crosstalks to achieve synergistic effects. In this review, we comprehensively summarize the pathogenic mechanisms of FGF-FGFR signaling in gastric adenocarcinoma together with the current targeted strategies in aberrant FGF-FGFR activated GC cases.
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http://dx.doi.org/10.3390/cells8060637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627225PMC
June 2019

Mechanotransduction and Cytoskeleton Remodeling Shaping YAP1 in Gastric Tumorigenesis.

Int J Mol Sci 2019 Mar 29;20(7). Epub 2019 Mar 29.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

The essential role of Hippo signaling pathway in cancer development has been elucidated by recent studies. In the gastrointestinal tissues, deregulation of the Hippo pathway is one of the most important driving events for tumorigenesis. It is widely known that Yes-associated protein 1 (YAP1) and WW domain that contain transcription regulator 1 (TAZ), two transcriptional co-activators with a PDZ-binding motif, function as critical effectors negatively regulated by the Hippo pathway. Previous studies indicate the involvement of YAP1/TAZ in mechanotransduction by crosstalking with the extracellular matrix (ECM) and the F-actin cytoskeleton associated signaling network. In gastric cancer (GC), YAP1/TAZ functions as an oncogene and transcriptionally promotes tumor formation by cooperating with TEAD transcription factors. Apart from the classic role of Hippo-YAP1 cascade, in this review, we summarize the current investigations to highlight the prominent role of YAP1/TAZ as a mechanical sensor and responder under mechanical stress and address its potential prognostic and therapeutic value in GC.
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http://dx.doi.org/10.3390/ijms20071576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480114PMC
March 2019

Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming.

Nat Commun 2019 01 18;10(1):335. Epub 2019 Jan 18.

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.

Hepatocellular carcinomas (HCC) exhibit distinct promoter hypermethylation patterns, but the epigenetic regulation and function of transcriptional enhancers remain unclear. Here, our affinity- and bisulfite-based whole-genome sequencing analyses reveal global enhancer hypomethylation in human HCCs. Integrative epigenomic characterization further pinpoints a recurrent hypomethylated enhancer of CCAAT/enhancer-binding protein-beta (C/EBPβ) which correlates with C/EBPβ over-expression and poorer prognosis of patients. Demethylation of C/EBPβ enhancer reactivates a self-reinforcing enhancer-target loop via direct transcriptional up-regulation of enhancer RNA. Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers, leading to drastic suppression of driver oncogenes and HCC tumorigenicity. Hepatitis B X protein transgenic mouse model of HCC recapitulates this paradigm, as C/ebpβ enhancer hypomethylation associates with oncogenic activation in early tumorigenesis. These results support a causal link between aberrant enhancer hypomethylation and C/EBPβ over-expression, thereby contributing to hepatocarcinogenesis through global transcriptional reprogramming.
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http://dx.doi.org/10.1038/s41467-018-08245-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338783PMC
January 2019

Targeting the miR-630/YAP1/ERK feedback loop in epidermal growth factor receptor-mutated lung adenocarcinomas.

J Thorac Dis 2018 Nov;10(Suppl 33):S4017-S4020

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, State Key laboratory of Digestive Diseases, The Chinese University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.21037/jtd.2018.10.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297487PMC
November 2018

MicroRNA-7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland.

J Pineal Res 2019 Apr 25;66(3):e12552. Epub 2019 Feb 25.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.

MicroRNAs, including microRNA-7 (miR-7), are important modulators of numerous gene expressions and the related biological processes. Melatonin is a key hormone regulating daily and seasonal rhythms, in which a variety of positive and negative regulatory factors, such as norepinephrine (NE) and leptin, are involved. However, the interactions among these factors and the mechanisms remain to be elucidated. The aims of the present study were to identify the functions and the related mechanisms of miR-7 in regulating melatonin synthesis and secretion through in vitro and in vivo experiments in pineal gland of pigs, which is an important animal model for agricultural and biomedical studies. Our results firstly show that miR-7 is specifically expressed in porcine pinealocytes and negatively regulates melatonin synthesis. The further functional studies show that the dynamic expression levels of miR-7 are contrary to the melatonin levels throughout the day, and the forced inhibition of endogenous miR-7 in porcine pinealocytes sharply increases arylalkylamine N-acetyltransferase (AANAT) expression by 80.0% (P = 0.0031) and melatonin levels by 81.0% (P = 0.0421), whereas miR-7 over-expression down-regulates AANAT expression by 38.6% (P = 0.0004) and melatonin levels by 37.6% (P = 0.0212). In addition, the miR-7 expression is up-regulated by leptin through the JAK/STAT3 signaling pathway, and the in vivo intracerebroventricular injection of leptin increases miR-7 expression by 80.0% (P = 0.0044) in porcine pineal glands and reduces melatonin levels by 57.1% (P = 0.0060) compared with the controls. This functional inhibition of melatonin synthesis by miR-7 is accomplished by its binding to the 3'-UTR of Raf1. Further, our results demonstrate that the RAF1/MEK/ERK signaling pathway mediates NE-induced AANAT expression, whereas leptin attenuates NE's function through miR-7. Taken together, the results demonstrated that leptin activates the JAK/STAT3 signaling pathway to increase the expression of miR-7, which acts as a negative regulatory molecule inhibiting NE-activated RAF1/MEK/ERK signaling pathway by targeting Raf1, resulting in decreased AANAT expression and melatonin synthesis. These findings suggest that miR-7 is a novel negative regulator of melatonin synthesis and links leptin- and NE-mediated signaling pathways in porcine pineal glands, which will contribute to our understanding in the establishment of the biological rhythms resulting from melatonin.
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http://dx.doi.org/10.1111/jpi.12552DOI Listing
April 2019

Fabrication of Few-Layered Porous Graphite for Removing Fluorosurfactant from Aqueous Solution.

Langmuir 2018 12 27;34(50):15181-15188. Epub 2018 Nov 27.

Guangdong Gaoming Industrial Innovation Research Institute , Foshan 528500 , P. R. China.

Due to the persistence, toxicity, and widespread occurrence of fluorosurfactants in the blood of general population, it is very important to develop recyclable and highly effective adsorbent material for their removal from aqueous solution. Herein, a new type of few-layered porous graphite (FPG) was fabricated as an adsorbent, and the adsorption characteristics of FPG toward potassium perfluorobutane sulfonate (PFBS), potassium perfluorohexane sulfonate (PFHxS), and potassium perfluorooctane sulfonate (PFOS) in environmental cleanup were evaluated under laboratory condition. The results indicated that the as-prepared FPG had sorption capacities of 1.22, 1.52, and 2.48 mmol g for PFBS, PFHxS, and PFOS, respectively, which were the highest adsorption values of PFHxS, PFBS, and PFOS on different kinds of today's carbon materials. The efficiency of FPG remained almost constant during the first five cycles of the adsorption-desorption process after heating. The outstanding adsorption performance of FPG was attributed to its unique physical properties, such as high porosity, high hydrophobicity, low density, and excellent heat stability. The findings presented herein indicated that FPG could serve as a promising adsorbent for the removal of fluorosurfactant in waste water.
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http://dx.doi.org/10.1021/acs.langmuir.8b03030DOI Listing
December 2018

An immune magnetic nano-assembly for specifically amplifying intercellular quorum sensing signals.

Colloids Surf B Biointerfaces 2018 Dec 18;172:197-206. Epub 2018 Aug 18.

Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, United States. Electronic address:

Quorum sensing (QS) enables intercellular communication after bacterial cells sense the autoinducers have reached or exceeded a critical concentration. Selectively amplifying specific bacterial "quorum" activity at a lower cell density is still a challenge. Here, we propose a novel platform of immune magnetic nano-assembly to amplify specific bacterial QS signaling via improving the bioavailability of autoinducers-2 (AI-2, furanosyl borate) from sender (wide-type, WT cells) to receiver (reporter cells). Antibody coated magnetic nanoparticle (MNPAB) was fabricated with an average diameter of 12 nm and a specific surface area of 96.5 m/g. The distribution efficiency of the antibody on the surface was 25.8 μg/m of magnetic nanoparticles. It was found that more than 3 × 10 of K12 serotype Escherichia coli (E. coli) reporter or WT cells were collected using 1 mg fabricated MNPAB at a saturated condition. The MNPAB not only captured E. coli WT cells but also brought them into proximity of E. coli (CT104, pCT6+pET-DsRed) reporter cells via magnetic attraction. The amplified QS signaling of the reporter cells by this immune magnetic nano-assembly was approximately 3 times higher than the nature QS signaling in cell suspension at optical density (OD) 0.08. This study foresees potential applications in amplifying specific biological QS signals based on a preprogrammed design.
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http://dx.doi.org/10.1016/j.colsurfb.2018.08.033DOI Listing
December 2018

An entrapped metal-organic framework system for controlled release of ethylene.

J Colloid Interface Sci 2019 Jan 21;533:207-215. Epub 2018 Aug 21.

Food Quality Laboratory, United States Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705, USA. Electronic address:

A novel gas storage and release system was developed for ethylene, an exogenous plant hormone that regulates fruit ripening and senescence. This system consists of a metal organic framework (MOF) core and an alginate-based shell. The MOF comprises a coordination complex of Al and [btc] ligands, which formed hexagonal structure (P6/mmc) with unit cell of 14.28 × 14.28 × 31.32 Å, as revealed by the X-ray diffraction analysis. Ethylene absorption isotherm exhibited an absorption capacity of 41.0 cm/g MOF at 25 °C and 101.3 kPa. After charging with ethylene, the MOFs are further entrapped in a close-knit bead formed with alginate-Fe(III) matrix, observed under a scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS). The alginate shell is degraded by exposing to 200 mM sodium citrate aqueous solution, triggering a continuous release of ethylene. With 20 mg of MOF, ethylene concentration reached 0.41-0.46 mg/L per mg MOF after 2.5 h. This is the first report regarding a controlled release of ethylene through degrading alginate-Fe(III) matrix rather than by changing the interfacial pore size of MOF under extreme conditions. This technology can enable precisely controlled and targeted applications of ethylene for food processing and agricultural applications.
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http://dx.doi.org/10.1016/j.jcis.2018.08.057DOI Listing
January 2019

FGF18, a prominent player in FGF signaling, promotes gastric tumorigenesis through autocrine manner and is negatively regulated by miR-590-5p.

Oncogene 2019 01 6;38(1):33-46. Epub 2018 Aug 6.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.

Fibroblast growth factors (FGFs) and their receptors are significant components during fundamental cellular processes. FGF18 plays a distinctive role in modulating the activity of both tumor cells and tumor microenvironment. This study aims to comprehensively investigate the expression and functional role of FGF18 in gastric cancer (GC) and elucidate its regulatory mechanisms. The upregulation of FGF18 was detected in seven out of eleven (63.6%) GC cell lines. In primary GC samples, FGF18 was overexpressed in genomically stable and chromosomal instability subtypes of GC and its overexpression was associated with poor survival. Knocking down FGF18 inhibited tumor formation abilities, induced G1 phase cell cycle arrest and enhanced anti-cancer drug sensitivity. Expression microarray profiling revealed that silencing of FGF18 activated ATM pathway but quenched TGF-β pathway. The key factors that altered in the related signaling were validated by western blot and immunofluorescence. Meanwhile, treating GC cells with human recombinant FGF18 or FGF18-conditioned medium accelerated tumor growth through activation of ERK-MAPK signaling. FGF18 was further confirmed to be a direct target of tumor suppressor, miR-590-5p. Their expressions showed a negative correlation in primary GC samples and more importantly, re-overexpression of FGF18 partly abolished the tumor-suppressive effect of miR-590-5p. Our study not only identified that FGF18 serves as a novel prognostic marker and a therapeutic target in GC but also enriched the knowledge of FGF-FGFR signaling during gastric tumorigenesis.
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http://dx.doi.org/10.1038/s41388-018-0430-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318220PMC
January 2019

Molecular structure, dynamics, and mechanical behavior of sodium aluminosilicate hydrate (NASH) gel at elevated temperature: a molecular dynamics study.

Phys Chem Chem Phys 2018 Aug;20(31):20695-20711

Department of Civil Engineering, Qingdao University of Technology, Qingdao 266033, China.

Sodium aluminosilicate hydrate (NASH) gel is the primary adhesive constituent in environmentally friendly geopolymer. In this study, to understand the thermal behavior of the material, molecular dynamics was utilized to investigate the molecular structure, dynamic property, and mechanical behavior of NASH gel subjected to temperature elevation from 300 K to 1500 K. The aluminosilicate skeleton in NASH gel provides plenty of oxygen sites to accept H-bond from the invading water molecules. Upon heating, around 18.2% of water molecules are decomposed and produce silicate and aluminate hydroxyls. About 87% of hydroxyls are associated with the aluminate skeleton, which weakens the Al-O bonds and disturbs the O-Al-O angle and the local structure, transforming it from an aluminate tetrahedron to a pentahedron and octahedron. With increasing temperature, both Al-O-Si and Si-O-Si bonds are stretched to be broken and the network structure of the NASH gel is gradually transformed into a branch and chain structure. Furthermore, the self-diffusivity of water molecules and sodium dramatically increases with the elevation of temperature, because the decrease in connectivity of the aluminosilicate network reduces the chemical and geometric restriction on the water and ions in NASH gel under higher temperatures. The high temperature also contributes to around 63% of the water molecules further dissociating and hydroxyl groups forming; meanwhile proton exchange between the water molecules and aluminosilicate network frequently takes place. In addition, a uniaxial tensile test was utilized to study the mechanical behavior of the NASH gel at different temperatures. During the tensile test, the aluminosilicate network was found to depolymerize into a branch or chain structure which plays a critical role in resisting the tensile loading. In this process, the breakage of the aluminosilicate skeleton is accompanied with hydrolytic reactions that further deteriorate the structure. Due to the reduction of the chemical bond stability at elevated temperature, both the tensile strength and stiffness of the NASH gel are weakened significantly. However, the ductility of the NASH gel is improved because of the higher extent of structural arrangement at the yield stage and partly due to the lower water attack. Hopefully, the present study can provide valuable molecular insights on the design of alkali-activated materials with high sustainability and durability.
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http://dx.doi.org/10.1039/c8cp03411gDOI Listing
August 2018

Ionic Strength and pH Responsive Permeability of Soy Glycinin Microcapsules.

Langmuir 2018 08 6;34(33):9711-9718. Epub 2018 Aug 6.

Department of Nutrition and Food Science, University of Maryland , College Park , Maryland 20742 , United States.

Recently, hollow protein microcapsules have been made simply by heating the microphase separated soy glycinin microdomains. However, the properties (e.g., mechanical properties and permeability) that relate to the application of these microcapsules are unknown. In this study, the permeability of the soy glycinin microcapsules was investigated by confocal laser scanning microscopy (CLSM), as influenced by ionic strength and pH using fluorescein isothiocyanate-dextran (FITC-dextran). The glycinin microcapsules kept the integrity between pH 1 and 11.5, swelled when pH was below 3 or above pH 11, dissociated at pH above 11.5 and deswelled slightly at pH 1. When the pH increased above 11, the permeability of the microcapsule significantly increased. Remarkably, when the pH was below the isoelectric point of glycinin (≈pH 5), FITC-dextran spontaneously accumulated inside the microcapsule with a significantly higher concentration than that in bulk solution, as evidenced by the strong intensity increase of fluorescence. This unique feature significantly increased the loading amount of FITC-dextran. The permeability of microcapsules was also increased by adding salt but less significant than by adjusting pH. The surface of the microcapsules became coarser when the permeability increased, which was revealed by scanning electron microscopy. These results show that soy glycinin has a great potential to be used as a wall material to fabricate hollow microcapsules that could find applications in biomedicine and food industry.
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http://dx.doi.org/10.1021/acs.langmuir.8b01559DOI Listing
August 2018

Genipin-crosslinked carboxymethyl chitosan nanogel for lung-targeted delivery of isoniazid and rifampin.

Carbohydr Polym 2018 Oct 7;197:403-413. Epub 2018 Jun 7.

Department of Light Chemical Engineering, Guangdong Polytechnic, Foshan 528041, PR China. Electronic address:

Lung-targeted genipin-crosslinked deacetylated chitosan (GEN-CS)/isoniazid (INH)/rifampin (RMP) nanogel particles (NGPs) were prepared as a treatment for tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB) to surmount the undesirable side effects and decrease the cytotoxicity of INH and RMP when being against MTB. The size, morphology, in vitro release property, long-term antibacterial performance, stability, in vitro cytotoxicity, in vivo toxicity, and in vivo release property of GEN-CS/INH/RMP NGPs inhalation powder were investigated. The results showed that the GEN-CS/INH/RMP NGPs inhalation powder exhibited extended antibacterial activity because of its long-term release of INH and RMP. A simplex GEN-CS/INH/RMP NGPs pulmonary dose led to the therapeutic drug concentration of 40%-60% in lung and other organs (<5%) for 24 h. Furthermore, this GEN-CS/INH/RMP NGPs lyophilized inhalation powder displayed lung-targeted property and lower in vivo toxicity. These results suggested that this GEN-CS/INH/RMP NGPs inhalation powder would be a more useful dosage form than separate dose of INH or RMP for MTB.
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http://dx.doi.org/10.1016/j.carbpol.2018.06.034DOI Listing
October 2018