Publications by authors named "Hai-Peng Chen"

15 Publications

  • Page 1 of 1

A Deep Learning Based Framework for Diagnosing Multiple Skin Diseases in a Clinical Environment.

Front Med (Lausanne) 2021 16;8:626369. Epub 2021 Apr 16.

Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce. This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients. Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding). Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task. The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors.
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http://dx.doi.org/10.3389/fmed.2021.626369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085301PMC
April 2021

Leaf morphology, photosynthesis and pigments change with age and sunlight in savin juniper.

Plant Biol (Stuttg) 2021 Mar 23. Epub 2021 Mar 23.

Department of Forest and Conservation Sciences, Faculty of Forestry, University of British Columbia, Vancouver, Canada.

• Savin juniper is an excellent species for desertification control in arid and semi-arid areas, where it typically establishes under the protection of nurse plants. Ultimately, established plants emerge into full sunlight as they grow, and this transition is accompanied by an increase in the preponderance of scale-like vs. needle-like leaf forms. • To test how age and variable sunlight environments affect shade tolerance in savin juniper, we established a pot study under field conditions with two age cohorts (1- and 4-year-old rooted scions) and three sunlight regimes (10%, 50% and 100% light transmittance). We measured growth, leaf parameters, photosynthesis, chlorophyll fluorescence and foliar pigments on a monthly basis (seven growing months per year, from 2015 to 2017). • Overall, there was little interaction for all variables, and both cohort and light regime had significant effects. Leaf form and spacing varied continuously, tending towards shorter, more closely spaced and more appressed scale leaves with higher dry leaf mass per area in older plants or under higher sunlight. There were no clear age-related patterns in carotenoids but both cohort and light had significant effects on gas exchange and chlorophyll fluorescence variables. • Savin juniper shows an intermediate tolerance to shade that changes with growth in that younger plants were less tolerant of full sun than older plants, consistent with its reliance on nurse plants for ultimate establishment in the open.
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http://dx.doi.org/10.1111/plb.13256DOI Listing
March 2021

The Distinction of Clinicopathological Characteristics, Treatment Strategy and Outcome in Colorectal Cancer Patients With Synchronous vs. Metachronous Bone Metastasis.

Front Oncol 2020 19;10:974. Epub 2020 Jun 19.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China.

The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC. We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS. Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis ( < 0.001). The median CSS was 11 months in both SBM and MBM group ( = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM. The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.
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http://dx.doi.org/10.3389/fonc.2020.00974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318073PMC
June 2020

Evaluation of clinical significance of claudin 7 and construction of prognostic grading system for stage II colorectal cancer.

World J Clin Cases 2020 Jun;8(11):2190-2200

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Background: Claudin 7 is often abnormally expressed in cancers and promotes the progression of some malignancies. However, the role of claudin 7 in stage II colorectal cancer (CRC) has not been studied.

Aim: To assess the expression and prognostic value of claudin 7 in stage II CRC.

Methods: We retrospectively studied 231 stage II CRC patients who underwent radical surgery at our hospital from 2013 to 2014. The protein expression level of claudin 7 was assessed and its relationship with clinicopathological features and prognosis was statistically analyzed. The independent prognostic factors were identified by Cox proportional hazards models. A prognostic grading system was constructed to stratify the survival of CRC patients.

Results: The expression of claudin 7 was significantly reduced in cancer tissues compared with normal tissues ( < 0.001), and its low expression was closely related to recurrence of the disease ( = 0.017). Multivariate analysis confirmed that claudin 7 low expression (claudin 7-low) ( = 0.028) and perineural invasion positivity (PNI+) ( = 0.026) were independent predictors of poor disease-free survival (DFS). A prognostic grading system based on the status of claudin 7 and PNI classified the patients into three prognostic grades: grade A (claudin 7-high and PNI-), grade B (claudin 7-low and PNI-, claudin 7-high and PNI+), and grade C (claudin 7-low and PNI+). The DFS was significantly different among the three grades (grade B grade A, = 0.032; grade C grade A, < 0.001; grade C grade B, = 0.040).

Conclusion: Claudin 7 can be used as a new prognostic marker to predict the DFS of patients with stage II CRC. The prognostic grading system with the addition of claudin 7 can further improve prognosis stratification of patients.
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http://dx.doi.org/10.12998/wjcc.v8.i11.2190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281043PMC
June 2020

B7-H3 immune checkpoint expression is a poor prognostic factor in colorectal carcinoma.

Mod Pathol 2020 11 8;33(11):2330-2340. Epub 2020 Jun 8.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Although PD-1/PD-L1 immunotherapy has been used successfully in treating many cancers, metastatic colorectal cancer (CRC) patients are not as responsive. B7-H3 is a promising target for immunotherapy and we found it to have the highest expression among B7-CD28 family members in CRC. Thus, the aim of the present study was to investigate B7-H3 expression in a large CRC cohort. B7-H3, B7-H4, and PD-L1 protein levels and differential lymphocyte infiltration were evaluated in tissue microarrays from 805 primary tumors and matched metastases. The relationships between immune markers, patient characteristics, and survival outcomes were determined. B7-H3 (50.9%) was detected in more primary tumors than B7-H4 (29.1%) or PD-L1 (29.2%), and elevated B7-H3 expression was associated with advanced overall stage. Co-expression of B7-H3 only with B7-H4 or PD-L1 was infrequent in primary tumors (6.3%, 5.7%, respectively). Moreover, B7-H3 in primary tumors was positively correlated with their respective expression at metastatic sites (ρ = 0.631; p < 0.001). No significant relationships between B7-H4 and PD-L1 and survival were observed; however, B7-H3 overexpression in primary tumors was significantly related to decreased disease-free survival. A positive relationship between B7-H3 expression and high density CD45RO T cell was observed in primary tumors, whereas B7-H4 and PD-L1 overexpression were related to CD3 T-cell infiltration. In conclusion, compared with B7-H4 and PD-L1, B7-H3 expression exhibited a higher prevalence and was significantly related to aggressiveness, worse prognosis and CD45RO T-cell infiltration in primary tumors. Further exploration of this potential target of immunotherapy in CRC patients is warranted.
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http://dx.doi.org/10.1038/s41379-020-0587-zDOI Listing
November 2020

A prognostic index model to individually predict clinical outcomes for colorectal cancer with synchronous bone metastasis.

J Cancer 2020 11;11(15):4366-4372. Epub 2020 May 11.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China.

The prognosis of synchronous bone metastasis (BM) in colorectal cancer (CRC) is poor and rarely concerned. A clinical tool to evaluate the prognosis and clinical outcomes for BM would be attractive in current clinical practice. A total of 342 CRC patients with synchronous BM were identified from Surveillance, Epidemiology, and End Results (SEER) database. The cancer specific survival (CSS) was estimated with the Kaplan-Meier method. Prognostic factors were identified from multivariate Cox model, and the final clinical nomogram was developed to predict the CSS. The concordance index (C-index) was used to assess the discriminative ability. Calibration curves were provided to internally validate the performance of the nomogram. The nomogram finally consisted of 6 prognostic factors including age, tumor grade, AJCC N stage, carcinoembryonic antigen (CEA) levels, primary tumor resection and chemotherapy, which translated the effects of prognostic factors into certain scores to predict the 1-, 2- and 3-year CSS for the synchronous BM in CRC patients. The nomogram presented a good accuracy for predicting the CSS with the C-index of 0.742. The calibration of the nomogram predictions was also accurate. This nomogram was accurate enough to predict the CSS of CRC patients with synchronous BM using readily available clinicopathologic factors and could provide individualized clinical decisions for both physicians and patients.
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http://dx.doi.org/10.7150/jca.40921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255384PMC
May 2020

A clinical model to predict the risk of synchronous bone metastasis in newly diagnosed colorectal cancer: a population-based study.

BMC Cancer 2019 Jul 17;19(1):704. Epub 2019 Jul 17.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China.

Background: The early detection of synchronous bone metastasis (BM) in newly diagnosed colorectal cancer (CRC) affects its initial management and prognosis. A clinical model to individually predict the risk of developing BM would be attractive in current clinical practice.

Methods: A total of 55,869 CRC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, of whom 317 patients were diagnosed with synchronous BM. Risk factors for BM in CRC patients was identified using multivariable logistic regression. A weighted scoring system was built with beta-coefficients (P < 0.05). A random sample of 75% of the CRC patients was used to establish the risk model, and the remaining 25% was used to validate its accuracy of this model. The performance of risk model was estimated by receiver operating curve (ROC) analysis.

Results: The risk model consisted of 8 risk factors including rectal cancer, poorly-undifferentiation, signet-ring cell carcinoma, CEA positive, lymph node metastasis, brain metastasis, liver metastasis and lung metastasis. The areas under the receiver operating curve (AUROC) were 0.903 and 0.889 in the development and validation cohort. Patients with scores from 0 to 4 points had about 0.1% risk of developing BM, and the risk increased to about 30% in patients with scores ≥15 points.

Conclusions: This clinical risk model is accurate enough to identify the CRC patients with high risk of synchronous BM and to further provide more individualized clinical decision.
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http://dx.doi.org/10.1186/s12885-019-5912-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637577PMC
July 2019

GGN Promotes Tumorigenesis by Regulating Proliferation and Apoptosis in Colorectal Cancer.

Pathol Oncol Res 2019 Oct 5;25(4):1621-1626. Epub 2019 Feb 5.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang Dist., Beijing, 100021, China.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. GGN is a germ cell-specific gene, but its function in CRC has been rarely reported to date. The aim of this study was to investigate the potential role of GGN in CRC tumorigenesis. Therefore, in this study, we examined the expression of GGN in CRC cell lines and tissues and its effects on cellular proliferation and apoptosis. We then explored the underlying mechanism. Our results showed that GGN was significantly overexpressed in both CRC cell lines and tissues. Silencing GGN robustly inhibited proliferation of CRC cells, and it also promoted apoptosis of CRC cells. Moreover, knockdown of GGN inhibited the expression of p-Akt in CRC cells. Taken together, these results showed that knockdown of GGN inhibits proliferation and promotes apoptosis of CRC cells through the PI3K/Akt signaling pathway. Our findings revealed for the first time a potential oncogenic role for GGN in CRC progress. This finding may provide a unique perspective on how a germ cell-specific gene might serve as a biomarker, or even as a therapeutic target, for CRC.
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http://dx.doi.org/10.1007/s12253-019-00595-3DOI Listing
October 2019

Dynamic modeling and characteristic analysis of piezoelectric rudder actuator.

Rev Sci Instrum 2019 Jan;90(1):016102

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, People's Republic of China.

In this note, dynamic equations of the piezoelectric rudder actuator are established using a numerical method, and the dynamic characteristics are analyzed. A simulation is performed using finite element software to verify the validity of the theory. The results show that an increase in axial force has significant amplification effects on the static displacement output of the bimorph and its rudder actuator, and the axial stiffness of the piezoelectric bimorph is evidently nonlinear against larger axial force. The response time of the rudder actuator is less affected by the axial force and remains in the order of milliseconds under the axial force of 0.85 times the buckling critical load.
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http://dx.doi.org/10.1063/1.5052595DOI Listing
January 2019

Current practice patterns of preoperative bowel preparation in colorectal surgery: a nation-wide survey by the Chinese Society of Colorectal Cancer.

World J Surg Oncol 2018 Jul 9;16(1):134. Epub 2018 Jul 9.

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The optimal preoperative bowel preparation for colorectal surgery remains controversial. However, recent studies have established that bowel preparation varies significantly among countries and even surgeons at the same institution. This survey aimed to obtain information on the current practice patterns of bowel preparation for colorectal surgery in China.

Methods: A paper-based survey was circulated to the members of the Chinese Society of Colorectal Cancer (CSCC). The survey responses were collected and analyzed. Statistical analysis was performed for all the categorical variables according to the responses to individual questions.

Results: Three hundred forty-one members completed the questionnaire. Regarding surgical practice, 203 (59.5%) performed > 50% of the colorectal operations laparoscopically or robotically; the use of mechanical bowel preparation (MBP) alone was significantly higher (63.5 vs 31.9%; P < 0.001). The respondents who performed > 200 colonic or rectal resections provided significantly more MBP alone (79.6 vs 39.1%, P < 0.001; 76.6 vs 43.2%, P < 0.001; respectively). Among hospitals with fewer than 500 beds, 52.4% of the respondents used MBP + oral antibiotics preparation (OAP) + enema, a significantly higher percentage than the respondents of hospitals with more than 500 beds (P < 0.001). Nearly 40% of the respondents prescribed OAP in regimens; meanwhile, 74.8% prescribed preoperative intravenous antibiotics.

Conclusions: The study demonstrates considerable variation among members from the CSCC. These findings should be considered when developing multicenter trials and to provide more definitive answers.
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http://dx.doi.org/10.1186/s12957-018-1440-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038260PMC
July 2018

Tunable dielectric transitions in layered organic-inorganic hybrid perovskite-type compounds: [NH(CH)Cl][CdClBr] (x = 0, 1/4, 1).

Dalton Trans 2018 May;47(20):7005-7012

Ordered Matter Science Research Center, Jiangsu Key Laboratory for Science and Applications of Molecular Ferroelectrics, Southeast University, Nanjing 211189, PR China.

Molecular bistable dielectric switches represent a class of highly desirable intelligent materials due to their sensitive switchable responses, simple and environmentally friendly processing, light weights, and mechanical flexibility. However, most of these switches can only work at a very low temperature, extremely limiting their potential applications. Herein, three layered organic-inorganic hybrid perovskite-type compounds of the general formula A2BX4, [NH3(CH2)2Cl]2[CdCl3Br] (1), [NH3(CH2)2Cl]2[CdCl4] (2) and [NH3(CH2)2Cl]2[CdBr4] (3), which display sensitive dielectric switching reversibility and remarkable switching anti-fatigue, have been successfully designed. Differential scanning calorimetry and dielectric measurements for 1 confirm its reversible phase transition at around 166 K. Through anion modulation, the phase transition temperatures of 2 and 3 can be greatly improved up to 237 K and 254 K, respectively. Structural analysis discloses that the phase transition temperature's shifts may result from the differences among the inorganic frameworks. Moreover, due to the significant order-disorder transitions of ammonium cations, the permittivities of 1, 2 and 3 change abruptly at around the phase transition points, making them excellent stimuli-responsive electrical switches. Such an anion-modulated method will open up new possibilities of highly efficiently tuning the phase transition temperature of molecular bistable dielectric switches.
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http://dx.doi.org/10.1039/c8dt00353jDOI Listing
May 2018

Sequential dielectric phase transitions induced by the vibrations of water molecules in an organic-inorganic hybrid halide (N-(2-ammoniumethyl)piperazinium) CuCl·2HO.

Dalton Trans 2017 Aug;46(31):10462-10468

Ordered Matter Science Research Center, Jiangsu Key Laboratory for Science and Applications of Molecular Ferroelectrics, College of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, P. R. China.

Organic-inorganic hybrids represent a new type of material showing promising properties. In this report, sequential dielectric transitions have been studied in an organic-inorganic hybrid halide, (N-2-AP)CuCl·2HO (N-2-AP = N-(2-ammoniumethyl)piperazinium) (1). The packing structure of 1 displays discrete [CuCl] rectangular pyramids and N-2-AP cations, which are linked by two water molecules, forming infinite hydrogen bond networks with inorganic and organic components along the b-axis. Characterization studies containing differential scanning calorimetry (DSC) measurements, variable-temperature X-ray diffraction and dielectric measurements were performed to investigate the phase transitions in 1. The deuterated sample of 1 (named 2) also exhibits a similar behavior to that in 1, but shows different phase transition temperatures in dielectric transitions. The arresting deuterated effect strongly confirms that the phase transitions in 1 are attributable to the local vibrations of water molecules resulting from the variation of hydrogen-bonding interactions.
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http://dx.doi.org/10.1039/c7dt01378gDOI Listing
August 2017

Controllable Structures Designed with Multiple-Dielectric Responses in Hybrid Perovskite-Type Molecular Crystals.

Inorg Chem 2017 Jun 31;56(12):7058-7064. Epub 2017 May 31.

Ordered Matter Science Research Center, College of Chemistry and Chemical Engineering, Southeast University , Nanjing 211189, People's Republic of China.

In this report, two new hybrid organic-inorganic perovskite-type compounds, (IBA)CdBr (1; IBA = isobutylammonium cation, i-CH-NH) and (IBA)CdBr (2), have been successfully synthesized by reasonable modulation of the ratio of the reactants. 1 with a one-dimensional (1D) chained structure presents sequential solid-state phase transitions, and 2 with a two-dimensional (2D) layered structure undergoes triple structural phase transitions. The phase transitions are attributable to the stepwise ordering process of the organic IBA cation of the title compounds, which also exhibit temperature-dependent dielectric transitions and dielectric anisotropies. Among the different structural environments, the dynamic motions of organic cations show distinct differences, driving the variation of physical properties.
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http://dx.doi.org/10.1021/acs.inorgchem.7b00662DOI Listing
June 2017

High-temperature structural phase transition coupled with dielectric switching in an organic-inorganic hybrid crystal: [NH(CH)Br]CdBr.

Dalton Trans 2017 Apr;46(14):4711-4716

Ordered Matter Science Research Center, Jiangsu Key Laboratory for Science and Applications of Molecular Ferroelectrics, Southeast University, Nanjing 211189, P.R. China.

Molecular bistable switches (electrical switches "ON" and "OFF") represent a class of highly desirable intelligent materials due to their sensitive switchable responses, simple and environmentally friendly processing, light weight, and mechanical flexibility. In particular, these switches above room temperature with potential practical application are rarely reported. In this work, a new zigzag chained organic-inorganic hybrid compound [NH(CH)Br]CdBr (1), which displays rapidly sensitive dielectric switching reversibility and remarkable switching antifatigue, has been successfully synthesized. Systematic characterization including differential scanning calorimetry measurements (DSC), dielectric measurements, and variable-temperature structural analyses was performed to reveal the phase transition of 1. A couple of reversible heat anomaly peaks at 335.6/323.8 K with a large hysteresis (ca. 11.8 K) were observed in the DSC curve, indicating the first-order type of phase transition. 1 exhibits an obvious dielectric switching at around 327 K, which makes 1 a potential switchable dielectric material. Variable-temperature structural analyses show that the cationic order-disorder motion is the main attribution for the phase transition of 1.
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http://dx.doi.org/10.1039/c6dt04799hDOI Listing
April 2017

MicroRNA-186 promotes macrophage lipid accumulation and secretion of pro-inflammatory cytokines by targeting cystathionine γ-lyase in THP-1 macrophages.

Atherosclerosis 2016 07 10;250:122-32. Epub 2016 May 10.

Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China. Electronic address:

Background And Aims: Several studies suggest that cardiomyocyte-enriched miR-186 is involved in cardiac injury and myocardial infarction, and also plays an important role in atherosclerotic diseases, but the underlying mechanism is unknown. Cystathionine-γ-lyase (CSE) is the predominant enzyme to produce H2S in the cardiovascular system. Here, miR-186 was identified to bind to the 3'UTR of CSE. In this study, we aimed at exploring whether miR-186 affects lipid accumulation and secretion of pro-inflammatory cytokines by targeting CSE and its underlying mechanism in human THP-1 macrophages and peripheral blood monocyte-derived macrophages (PBMDM). PBMDM just as a control group for the comparison with the THP-1 macrophages.

Methods: MiR-186 target genes, CSE 3'UTR sequence and free energy were predicted and analyzed by bioinformatics analyses and dual-luciferase reporter assays. The expression of CSE mRNA and protein were measured by real-time quantitative PCR and western blot analyses. The lipid accumulation in THP-1 macrophages was detected by high performance liquid chromatography (HPLC). The effects of miR-186 on secretion of IL-6, IL-1β and TNF-α were examined by ELISA. Endogenous H2S was detected by spectrophotometry. Using small interfering RNA (siRNA) approach to decrease the expression of CSE protein and mRNA.

Results: We found that miR-186 directly inhibited CSE protein and mRNA expression through targeting CSE 3'UTR by bioinformatics analyses and dual-luciferase reporter assays. HPLC assays showed that miR-186 increased the lipid accumulation in human THP-1 macrophages. We also showed that miR-186 enhanced secretion of pro-inflammatory cytokines in human THP-1 macrophages. Using siRNA approach, we found that CSE siRNA could inhibit the miR-186 inhibitor-induced decrease in the expression of LPL protein and mRNA in human THP-1 macrophages, which was accompanied a decrease in the level of H2S.

Conclusions: MicroRNA-186 promotes macrophage lipid accumulation and pro-inflammatory cytokine secretion by targeting cystathionine γ-lyase in THP-1 macrophages.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.04.030DOI Listing
July 2016