Publications by authors named "Wen-wen Liu"

42 Publications

Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer.

Front Oncol 2021 22;11:699889. Epub 2021 Jul 22.

Institute of Life Science and Green Development, Hebei University, Baoding, China.

Purpose: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC.

Methods: Correlation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity .

Results: PTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression .

Conclusion: This study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression EGFR/Akt signaling pathway.
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http://dx.doi.org/10.3389/fonc.2021.699889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339706PMC
July 2021

Precise diagnosis of three top cancers using dbGaP data.

Sci Rep 2021 01 12;11(1):823. Epub 2021 Jan 12.

Huaiyin Institute of Technology, Huaian, 223003, China.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.
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http://dx.doi.org/10.1038/s41598-020-80832-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804208PMC
January 2021

"Development and application of analytical detection techniques for droplet-based microfluidics"-A review.

Anal Chim Acta 2020 May 9;1113:66-84. Epub 2020 Mar 9.

William R. Wiley Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, P.O. Box 999, Richland, WA, 99352, USA. Electronic address:

Droplet-based microfluidics has emerged as a powerful platform for high-throughput and low-volume analysis and screening. At present, droplet-based microfluidics is transitioning from the proof-of-concept stage to real-world applications. During this process, analytical detection techniques play indispensable roles for successfully implementing droplet-based chemical or biological assays. In this review, we provide an overview of recent developments in analytical techniques for droplet analysis and elucidate the advantages and limitations of each technique. We cover the majority of technology categories, including optical detection, electrical detection, mass spectrometry, and nuclear magnetic resonance spectroscopy. Additionally, we highlight new research areas that have been enabled by these technical advances. Finally, we provide perspectives on both future technological directions and potential enabling applications.
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http://dx.doi.org/10.1016/j.aca.2020.03.011DOI Listing
May 2020

Single‑cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction.

Oncol Rep 2020 Apr 18;43(4):1278-1288. Epub 2020 Feb 18.

Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Single‑cell RNA sequencing (scRNA‑seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA‑seq. Clustering methods were used to separate leukemia cells into different sub‑populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT‑rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA‑seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.
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http://dx.doi.org/10.3892/or.2020.7507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057921PMC
April 2020

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages.

FASEB J 2020 05 10;34(5):7144-7159. Epub 2020 Apr 10.

Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, China.

Disrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1β. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis.
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http://dx.doi.org/10.1096/fj.201903073RDOI Listing
May 2020

BMAL1 regulation of microglia-mediated neuroinflammation in MPTP-induced Parkinson's disease mouse model.

FASEB J 2020 05 4;34(5):6570-6581. Epub 2020 Apr 4.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1 mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1 mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.
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http://dx.doi.org/10.1096/fj.201901565RRDOI Listing
May 2020

Osteogenic activity of a titanium surface modified with silicon-doped titanium dioxide.

Mater Sci Eng C Mater Biol Appl 2020 May 21;110:110682. Epub 2020 Jan 21.

Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address:

Titanium and its alloys are the most widely used implants in clinical practice. However, their bioactivity is unsatisfactory, and the effect of osteogenesis on the bonding interface between the implant and bone needs to be further improved. In this study, a coating consisting of microporous titanium doped with silicon (Si-TiO) was successfully created by microarc oxidation (MAO), and Si was evenly distributed on the surface of the coating. The surface morphology, roughness, and phase composition of the Si-TiO microporous coating were similar to those of the Si-free doped MAO coatings. The Si-TiO microporous coating can promote osteoblast adhesion, spreading, proliferation and differentiation. More importantly, the integrin β1-FAK signaling pathway may be involved in the regulatory effect of the coating on osteoblasts. Further studies in vivo indicated that the Si-TiO microporous coating could improve early stage osseointegration. In conclusion, the Si-TiO microporous coating is a feasible way to improve the osteogenic abilities of Ti implants to potentially promote clinical performance.
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http://dx.doi.org/10.1016/j.msec.2020.110682DOI Listing
May 2020

[Emission Characteristics and Ozone Formation Potential of VOCs in Printing Enterprises in Beijing-Tianjin-Hebei].

Huan Jing Ke Xue 2019 Sep;40(9):3942-3948

Beijing Key Laboratory of Urban Atmospheric Volatile Organic Compounds Pollution Control and Application, Beijing Municipal Research Institute of Environmental Protection, Beijing 100037, China.

In this study, 23 typical printing enterprises were selected in Beijing-Tianjin-Hebei. Through gas chromatography-mass spectrometry/flame ionization detection (GC-MS/FID), 46 sets of analysis results were obtained to quantitatively analyze the emissions characteristics of volatile organic compounds (VOCs) and the ozone generation potential of these printing enterprises. The results show that the emission concentrations of total VOCs (TVOCs) in exhaust funnels of the printing enterprises varied greatly, ranging from 3.3 mg·m to 755.0 mg·m. In the printing stations of printing enterprises, the emission concentrations of VOCs were 129.7-958.4 mg·m and 19.1-113.7 mg·m in packaging and printing enterprises and publications printing enterprises, respectively. The concentration of VOCs emitted by packaging and printing enterprises was significantly higher than that of publications printing enterprises, which is related to the use of solvent-based inks. In terms of VOC composition, oxygen-containing VOCs were the primary type of those emitted by the printing station of packaging and printing enterprises and publications printing enterprises, which accounted for a ratio of 32.6%-99.4%, followed by alkanes. In terms of ozone generation potential, the average of ozone formation potential (OFP) of the printing enterprises was 505.5 mg·m, in which the packaging and printing enterprises was 564.1 mg·m, and the publication printing enterprises was 52.9 mg·m. The average VOC source reactivity (SR) emitted from the printing process was 1.24 g·g; that is, 1.24 g of O was formed owing to the unit mass of VOC emission, of which the packaging and printing enterprises was 1.70 g·g, and the publication printing enterprises was 0.89 g·g. According to the OFP and SR, the use of environmentally friendly ink can reduce the generation of O and promote air quality improvement.
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http://dx.doi.org/10.13227/j.hjkx.201901043DOI Listing
September 2019

[Source Profiles of Volatile Organic Compounds (VOCs) from Typical Solvent-based Industries in Beijing].

Huan Jing Ke Xue 2019 Oct;40(10):4395-4403

Key Laboratory of Urban Atmospheric Volatile Organic Compounds Pollution Control and Application, Beijing Municipal Research Institute of Environmental Protection, Beijing 100037, China.

Based on the demand for a volatile organic compounds (VOCs) emissions inventory for Beijing and for the reduction in VOC emissions, the three major solvent-based industries of automobile manufacturing, furniture manufacturing, and publication printing were selected for this study. In each case, emissions link negative pressure sampling was used in combination with laboratory-based GC-MS/FID to obtain the VOC spectra. The results show that there are significant differences in the emission of VOCs from the main stages of automobile manufacturing. Specifically, the paint-coating process was dominated by the emission of oxygenated VOCs and aromatic hydrocarbons, accounting for 71.26% and 27.14% of total VOC emissions, respectively. The proportion of aromatic hydrocarbons emitted during the varnishing process was very large (84.10%), which were mainly composed of the benzene series. The differences in VOC emissions during different stages of the furniture manufacturing process were small, mainly consisting of oxygenated VOCs and aromatic hydrocarbons, which accounted for 55.08% and 18.98% of the total, respectively. Of these, alcohols and esters were the main components. VOCs emitted from different stages of the publication printing process could not be monitored separately. Thus, the VOCs in the mixed exhaust gas from this process were mainly composed of alkanes and oxygenated VOCs, which accounted for 47.29% and 44.57% of the total emissions, respectively.
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http://dx.doi.org/10.13227/j.hjkx.201901128DOI Listing
October 2019

[Clinical observation on the inflammatory indexes in septic gastrointestinal dysfunction treated with acupuncture at Jiaji (EX-B 2)].

Zhongguo Zhen Jiu 2019 Oct;39(10):1055-8

Department of Intensive Care Medicine, TCM Hospital of Changxing County, Huzhou 313000, Zhejiang Province, China.

Objective: To evaluate the effect on the inflammatory indexes of septic gastrointestinal dysfunction treated with acupuncture at Jiaji (EX-B 2).

Methods: A total of 118 patients of septic gastrointestinal dysfunction were randomized into an observation group and a control group, 59 cases in each one. In the control group, mosapride citrate was prescribed for oral administration, 5 mg each time, 3 times a day, bifidobacterium triple viable capsules, 420 mg each time, twice a day, intravenous drip with omeprazole, 40 mg, twice a day. Additionally, the antibiotics and the symptomatic treatment were selected rationally for maintaining the functions of the important organs, e.g. heart, lung, brain and kidney, and water-electrolyte balance. In the observation group, on the routine management as the control group, acupuncture at Jiaji (EX-B 2, T-T) was added, the needles were retained for 30 min in each treatment, once a day, 10 days as one course and 1 course was required. Separately, on the 1st, 3rd, 6th and 10th days of treatment, the white blood cell (WBC) count, the levels of hypersensitive C-reactive protein (hs-CRP) and procalcitonin (PCT) were observed, the enteral nutrition feeding dose and gastrointestinal dysfunction score before and after treatment as well as the clinical effect were assessed in the two groups.

Results: The differences were not significant in the indexes mentioned above on 1st and 3rd days of treatment between the two groups (>0.05). On the 6th and 10th days of treatment, regarding the gastrointestinal dysfunction score and inflammatory indexes count, the results in the observation group were lower than the control group (all <0.05), and feeding dose in the observation group was higher than the control group (<0.05). After treatment, the gastrointestinal dysfunction scores and inflammatory indexes count were all reduced and feeding dose was increased as compared with those before treatment in the patients of the two groups (all <0.05). After treatment, the total effective rate was 91.5% (54/59) in the observation group, higher than 76.3% (45/59) in the control group (<0.05).

Conclusion: Acupuncture at Jiaji (EX-B 2) points achieves the satisfactory effect on septic gastrointestinal dysfunction and reduces the inflammatory indexes count.
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http://dx.doi.org/10.13703/j.0255-2930.2019.10.006DOI Listing
October 2019

Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT/VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma.

Front Oncol 2019 11;9:862. Epub 2019 Sep 11.

Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, China.

OTUD7B, a multifunctional deubiquitinylase, plays an essential role in inflammation and proliferation signals. However, its function in lung cancer remains largely unknown. The aim of this study was to evaluate the prognostic significance of OTUD7B in patients with lung adenocarcinoma and squamous carcinoma and to characterize its molecular mechanisms in lung cancer progression and metastasis. Two tissue microarrays containing 150 pairs of lung squamous carcinoma and matched adjacent non-cancer tissues, and one tissue microarray containing 75 pairs of lung adenocarcinoma and adjacent non-cancer tissues were included, and immunohistochemical staining was performed to assess the clinical relevance of OTUD7B in non-small cell lung cancer. OTUD7B is highly expressed in both lung squamous carcinoma and adenocarcinoma and correlates with a worse prognosis. MTT proliferation, colony formation, migration and invasion assays and immunoblotting assay in NCI-H358 and A549 cell lines suggested that OTUD7B enhances EGF-induced Akt signal transduction and promotes lung cancer cell proliferation and migration. Immunohistochemical staining of large-scale lung cancer subjects (171 cases) revealed positive correlation of OTUD7B and VEGF expression. ELISA and tube formation assay revealed OTUD7B promotes VEGF production and angiogenesis. NCI-H358 tumor model demonstrated OTUD7B is required for lung tumor progression by facilitating activation of Akt signaling. These findings collectively identified OTUD7B as an independent predictive factor for the prognosis of non-small cell lung cancer and revealed OTUD7B promotes lung cancer cell proliferation and metastasis via Akt/VEGF signal pathway.
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http://dx.doi.org/10.3389/fonc.2019.00862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749047PMC
September 2019

Factors Influencing Aspirin Hyporesponsiveness in Elderly Chinese Patients.

Med Sci Monit 2019 Jul 13;25:5191-5200. Epub 2019 Jul 13.

Department of Geriatrics, Peking University First Hospital, Peking University, Beijing, China (mainland).

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.
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http://dx.doi.org/10.12659/MSM.917654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647928PMC
July 2019

miR-34b-3p May Promote Antiplatelet Efficiency of Aspirin by Inhibiting Thromboxane Synthase Expression.

Thromb Haemost 2019 Sep 2;119(9):1451-1460. Epub 2019 Jul 2.

Department of Geriatrics, Peking University First Hospital, Xicheng District, Beijing, China.

Aspirin has been widely used for the prevention of cardiovascular diseases, but its antiplatelet efficiency varies between individuals. The present study aimed to evaluate response to aspirin based on gene profiles as well as potential regulating pathways using human blood samples and cell lines. Platelet function in patients 50 years or older with coronary artery disease on 100 mg/day aspirin was measured by light transmission aggregometry (LTA) of arachidonic acid (AA)-induced platelet aggregation. The expression of eight candidate genes-PTGS1/COX1, PLA2G4A, PLA2G6, PLA2G7, TBXAS1, TBXA2R, PTGIR, and ITGA2B-and the ingredients involved in AA metabolism were analyzed. Our data showed that the expressions of thromboxane A synthase 1 (TBXAS1), thromboxane synthase (TXS), and thromboxane B (TXB) were increased in the upper quartile of platelet aggregation (LTA-AA_Q4) group compared with the lower quartile of platelet aggregation (LTA-AA_Q1) group. Our bioinformatics analysis suggested that TBXAS1 was targeted by miR-34b-3p via binding to its 3'-UTR, which was subsequently verified experimentally. Although overexpression of miR-34b-3p exhibited no apparent effect on cell proliferation, inhibition of miR-34b-3p promoted megakaryocyte viability. Our data demonstrated that the expression of TBXAS1 was higher in the aspirin hyporesponsiveness group than that in the hyperresponsiveness group, suggesting that high expression of TBXAS1 may be associated with aspirin hyporesponsiveness. miR-34b-3p may regulate the platelet and aspirin response by suppressing TBXAS1 expression and megakaryocyte proliferation.
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http://dx.doi.org/10.1055/s-0039-1692681DOI Listing
September 2019

[Clinical trials of acupuncture of Jiaji (EX-B2) for treatment of gastrointestinal dysfunction in sepsis patients].

Zhen Ci Yan Jiu 2019 Jan;44(1):43-6

Intensive Care Unit, Changxing County Hospital of Traditional Chinese Medicine, Huzhou 313000, Zhejiang Province, China.

Objective: To observe the clinical therapeutic effect of acupuncture of Huatuo Jiaji (EX-B2) in the treatment of gastrointestinal dysfunction in sepsis patients, aiming at providing new clinical approach and evidence for improving septic gastrointestinal activity.

Methods: A total of 40 patients with septic gastrointestinal dysfunction who met our inclusive criteria were randomly divided into control group and treatment group (=20 cases in each). Patients in the control group received routine treatment of nasogastric mosapride citrate (5 mg/time, three times a day) and tifidobacterium triple viable capsules (420 mg, twice a day), intravenous infusion of omeprazole (40 mg, twice a day), rational dose of antibiotics, maintenance treatment of functions of the heart, lung, brain, kidney and other important organs and water electrolyte balance, as well as symptomatic treatment. Patients of the treatment group were treated by acupuncture of EX-B2 on the basis of routine treatment mentioned above in the control group. The acupuncture needle was inserted into EX-B2, twirled for a while and retained for 30 min, once a day for 10 successive days. The acute physiology and chronic health evaluation (APACHE II) score was given according to Knaus and colleagues' method, the intra-abdominal pressure was detected by using a manometer which was connected to an inserted canal in the urinary bladder, and the intragatric residul volume detected by using an injection syriange pumping via a nasal feeding tube.

Results: After the treatment, the APACHE II score, intra-abdominal pressure and intragastric residual volume on day 10 were significantly decreased in both groups in comparison with their own pre-treatment (<0.05), while the borborygmus levels on day 10 were considerably increased in both groups relevant to their own pre-treatment (<0.05). The APACHE II scores, intra-abdominal pressure and intragastric residual volume on day 3, 6 and 10 were significantly lower in the treatment group than those in the control group (<0.05), whereas the borborygmus levels at the 3 , 6 and 10 day in the treatment group were apparently higher than those of the control group (<0.05)..

Conclusion: Acupuncture stimulation of EX-B2 has a good curative effect in improving gastrointestinal dysfunction in sepsis patients.
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http://dx.doi.org/10.13702/j.1000-0607.170579DOI Listing
January 2019

A Critical Role of Autophagy in Regulating Microglia Polarization in Neurodegeneration.

Front Aging Neurosci 2018 20;10:378. Epub 2018 Nov 20.

Department of Neurology, Suzhou Clinical Research Center of Neurological Disease, Suzhou Municipal Hospital of Nanjing Medical University, Suzhou, China.

Neuroinflammation and autophagy dysfunction are closely related to the development of neurodegeneration such as Parkinson's disease (PD). However, the role of autophagy in microglia polarization and neuroinflammation is poorly understood. TNF-α, which is highly toxic to dopaminergic neurons, is implicated as a major mediator of neuroinflammation in PD. In this study, we found that TNF-α resulted in an impairment of autophagic flux in microglia. Concomitantly, an increase of M1 marker (iNOS/NO, IL-1β, and IL-6) expression and reduction of M2 marker (Arginase1, Ym1/2, and IL-10) were observed in TNF-α challenged microglia. Upregulation of autophagy via serum deprivation or pharmacologic activators (rapamycin and resveratrol) promoted microglia polarization toward M2 phenotype, as evidenced by suppressed M1 and elevated M2 gene expression, while inhibition of autophagy with 3-MA or Atg5 siRNA consistently aggravated the M1 polarization induced by TNF-α. Moreover, Atg5 knockdown alone was sufficient to trigger microglia activation toward M1 status. More important, TNF-α stimulated microglia conditioned medium caused neurotoxicity when added to neuronal cells. The neurotoxicity was further aggravated when Atg5 knockdown in BV2 cells but alleviated when microglia pretreatment with rapamycin. Activation of AKT/mTOR signaling may contribute to the changes of autophagy and inflammation as the AKT specific inhibitor perifosine prevented the increase of LC3II (an autophagic marker) in TNF-α stimulated microglia. Taking together, our results demonstrate that TNF-α inhibits autophagy in microglia through AKT/mTOR signaling pathway, and autophagy enhancement can promote microglia polarization toward M2 phenotype and inflammation resolution.
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http://dx.doi.org/10.3389/fnagi.2018.00378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256089PMC
November 2018

Complete plastome sequences of Merr. and Merr. (Ebenaceae): two endemic species in Hainan Province, China.

Mitochondrial DNA B Resour 2018 Oct 30;3(2):1205-1207. Epub 2018 Oct 30.

Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, Institute of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China.

is the largest genus (about 485 species) in Ebenaceae. It is a deciduous or evergreen tree or shrub. It grows in pantropical and extending into temperate regions. Here, we report and characterize the complete plastid genome sequences of Merr. and Merr. in an effort to provide genomic resources useful for promoting their systematics research and potential economic development. The complete plastome of is 157,946 bp in length, including two Inverted Repeat (IR) regions of 26,081 bp, a Large Single-Copy (LSC) region of 87,387 bp, and a Small Single-Copy (SSC) region of 18,397 bp. The plastome contains 114 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA genes, and four unique rRNA genes. The overall A/T content in the plastome of is 62.60%. The complete plastome of is 157,999 bp in length, including two Inverted Repeat (IR) regions of 26,077 bp, a Large Single-Copy (LSC) region of 87,523 bp, and a Small Single-Copy (SSC) region of 18,322 bp. The plastome contains 114 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA genes, and four unique rRNA genes. The overall A/T content in the plastome of is 62.60%. The complete plastome sequences of and will provide a useful resource for the conservation genetics of the two species as well as for the phylogenetic studies of
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http://dx.doi.org/10.1080/23802359.2018.1524724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799653PMC
October 2018

A Lithium-Sulfur Battery using a 2D Current Collector Architecture with a Large-Sized Sulfur Host Operated under High Areal Loading and Low E/S Ratio.

Adv Mater 2018 Nov 4;30(46):e1804271. Epub 2018 Oct 4.

Chemical Sciences and Engineering Division, Argonne National Laboratory, 9700 Cass Ave, Lemont, IL, 60439, USA.

While backless freestanding 3D electrode architectures for batteries with high loading sulfur have flourished in the recent years, the more traditional and industrially turnkey 2D architecture has not received the same amount of attention. This work reports a spray-dried sulfur composite with large intrinsic internal pores, ensuring adequate local electrolyte availability. This material offers good performance with a electrolyte content of 7 µL mg at high areal loadings (5-8 mg cm ), while also offering the first reported 2.8 µL mg (8 mg cm ) to enter into the second plateau of discharge and continue to operate for 20 cycles. Moreover, evidence is provided that the high-frequency semicircle (i.e., interfacial resistance) is mainly responsible for the often observed bypassing of the second plateau in lean electrolyte discharges.
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http://dx.doi.org/10.1002/adma.201804271DOI Listing
November 2018

Using generalized additive models to investigate factors influencing cyanobacterial abundance through phycocyanin fluorescence in East Lake, China.

Environ Monit Assess 2018 Sep 20;190(10):599. Epub 2018 Sep 20.

Laboratory of Basin Hydrology and Wetland Eco-restoration, China University of Geosciences, Wuhan, 430074, China.

East Lake is a shallow lake (in Wuhan, China) where cyanobacteria blooms occurred frequently from 1970 to 1985. During the study period, all Carlson trophic state index values were > 50, indicating that East Lake is in a eutrophic state. In this study, phycocyanin concentrations were measured through phycocyanin fluorometry for rapid assessment of cyanobacterial abundance. The smoothing splines of the optimal generalized additive model (GAM) indicated that Secchi depth (SD), total phosphorus (TP) and dissolved oxygen (DO) concentrations, electrical conductivity (EC), chemical oxygen demand (COD), and ratios of total nitrogen (TN) to TP (TN:TP) were the main environmental factors in a moderate nonlinear relationship with cyanobacterial phycocyanin concentrations in East Lake. The shape of the GAM smoother can be used to quantify the relationship between a response variable and an explanatory variable in the scatterplot. Phycocyanin concentrations were sharply and negatively related to both SD and EC when the SD was 20-80 cm and EC was > 270 mg/L. Phycocyanin concentrations increased with concentrations of TP, DO, and COD. Phycocyanin concentrations increased sharply with TP concentrations when TP concentrations were > 0.10 mg/L and approached to a constant when DO concentrations were > 8.20 mg/L. Approximately, 85% of the phycocyanin concentrations were negatively correlated with TN:TP of < 26. In summary, organic compounds and TP were inferred to the key factors limiting the potential growth of cyanobacteria in East Lake. These change points/thresholds of smoothing splines of aforementioned variables may serve as a framework for managing the cyanobacterial growth.
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http://dx.doi.org/10.1007/s10661-018-6981-zDOI Listing
September 2018

[Genotype Analysis of Patients with Thalassemia in Sanya Area of Hainan Province in China].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Aug;26(4):1146-1150

Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China Department of Hematology, Hainan Branch of Chinese PLA General Hospital, Sanya 572000, Hainan Province, China E-mail:

Objective: To explore the frequency and spectrum of thalassemia gene mutations of the population in Sanya area of Hainan province in China.

Methods: The type and frequency of gene mutation in 1060 patients with suspected thalassemia were analyzed by Gap-PCR and reverse dot blot (RDB).

Results: The detection on mutation of thalassemia gene were found in 539 suspected thalassemia patients, the total detected rate was 50.85% (539/1060), out of them 330 (31.13%) were diagnosed with α-thalassemia, 162 (15.28%) with β-thalassemia, and 47 (4.43%) as carriers of both α and β-thalassemia. In α-thalassemia patients, genotype were as follows in proper order--SEA/αα (9.25%)、-α /αα (5.94%),HbH (5.56%),-α /αα (5.00%),-α /-α (2.36%),-α /-α (1.70%), and -α/-α(1.32%). In β-thalassemia patients, there were 9 gene mutations: CD41-42 (9.8%), CD17 (1.32%), 654 (1.23%), CD71-72 (1.23%), IVS-II-654 (1.04%), -28 (0.37%), CD43 (0.19%), -29 (0.18%) and βE (0.09%). In the α and β composite thalassemia there were 12 genotypes. The -α/αα was the most common genotype co-existed with β-thalassemia (1.70%), followed by the -α /αα genotype (0.94%).

Conclusion: The data of this study provide the frequency and the spectrum of thalassemia gene mutations in the sanya area of Hainan province, which can contribute to set up the strategies for the prevention and control of thalassemia in this area.
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http://dx.doi.org/10.7534/j.issn.1009-2137.2018.04.033DOI Listing
August 2018

Potential health risk assessment through ingestion and dermal contact arsenic-contaminated groundwater in Jianghan Plain, China.

Environ Geochem Health 2018 Aug 1;40(4):1585-1599. Epub 2018 Feb 1.

School of Environmental Studies, China University of Geosciences, Wuhan, 430074, China.

Groundwater contamination with high arsenic (As) levels has caused serious health problem in Jianghan Plain. This study presents a framework to evaluate the results and their probable influencing factors of non-carcinogenic risk and carcinogenic risk in Shahu Village. An appropriate health risk assessment for residents exposing to As through ingestion and dermal contact pathways is also discussed in the paper. Hazard quotient (HQ) and target cancer risk (TR) are adopted to compute the non-carcinogenic and carcinogenic effects for residents, respectively. Monte Carlo simulation technique is used to quantify the uncertainty of the risk assessment. The assessment results show that the HQs and TRs of 10-m-deep and 25-m-deep wells exhibit seasonal variations with higher values in rainy season and lower values in dry season. The HQ values exceeding 1 at the depths of 10 (from 0.09 to 23.21 m) and 25 m (from 0.29 to 130.55 m) account for 61 and 94%, respectively, which associate with the As contents distribution in the aquifer sediments. The estimated TR values at the depths of 10 (from 3.86E-05 to 1.04E-02) and 25 m (from 1.32E-04 to 5.87E-02) exceeding the highest acceptable standard (10) account for 95 and 100%, respectively. Comparison of the two exposure pathways, the ingestion exposure contributes much more than the dermal contact exposure for both non-carcinogenic risk and carcinogenic risk. The results of sensitivity analysis indicate that a more accurate measurement and better definition of probability distributions for As concentration in the groundwater can increase the accuracy of health risk assessment in Jianghan Plain. The findings demonstrate the importance of the drinking water safety, and the government should take measures to ensure the drinking water safety.
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http://dx.doi.org/10.1007/s10653-018-0073-4DOI Listing
August 2018

Discovery of novel propargylamine-modified 4-aminoalkyl imidazole substituted pyrimidinylthiourea derivatives as multifunctional agents for the treatment of Alzheimer's disease.

Eur J Med Chem 2018 Jan 10;143:33-47. Epub 2017 Aug 10.

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China. Electronic address:

A series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-3) were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy, and their potential was evaluated through various biological experiments. Among these derivatives, compound 1b displayed good selective inhibitory activity against AChE (vs BuChE, IC = 0.324 μM, SI > 123) and MAO-B (vs MAO-A, IC = 1.427 μM, SI > 35). Molecular docking study showed that the pyrimidinylthiourea moiety of 1b could bind to the catalytic active site (CAS) of AChE, and the propargylamine moiety interacted directly with the flavin adenine dinucleotide (FAD) of MAO-B. Moreover, 1b demonstrated mild antioxidant ability, good copper chelating property, effective inhibitory activity against Cu-induced Aβ aggregation, moderate neuroprotection, low cytotoxicity, and appropriate blood-brain barrier (BBB) permeability in vitro and was capable of ameliorating scopolamine-induced cognitive impairment in mice. These results indicated that 1b has the potential to be a multifunctional candidate for the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1016/j.ejmech.2017.08.025DOI Listing
January 2018

Femtomole-Scale High-Throughput Screening of Protein Ligands with Droplet-Based Thermal Shift Assay.

Anal Chem 2017 06 1;89(12):6678-6685. Epub 2017 Jun 1.

Institute of Microanalytical Systems, Department of Chemistry and Innovation Center for Cell Signaling Network, Zhejiang University , Hangzhou, 310058, China.

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here, we developed a microfluidic droplet-based thermal shift assay (dTSA) system for high-throughput screening of small-molecule protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 × 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96- or 384-well plate-based systems. We also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations. To demonstrate its potential in drug discovery, we applied the dTSA system in screening inhibitors of human thrombin with a commercial library containing 100 different small molecule compounds, and two inhibitors were successfully identified and confirmed.
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http://dx.doi.org/10.1021/acs.analchem.7b00899DOI Listing
June 2017

Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease.

Chin Med J (Engl) 2017 May;130(9):1085-1092

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.

Background: Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.

Methods: The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days. Rotarod test, footprint test, and open-field test were carried out to evaluate the motor function. Striatum, suprachiasmatic nucleus (SCN), liver, and plasma were collected at 6:00, 12:00, 18:00, and 24:00. Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes. Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin. High-performance liquid chromatography was used to measure the neurotransmitters. Analysis of variance was used for data analysis.

Results: L-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test ( P < 0.01, P < 0.001, respectively). After L-DOPA treatment, Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 ( P < 0.01) and 24:00 ( P < 0.001). In the striatum, the expression of Bmal1, Rorα was lower than that in the 6-OHDA group at 18:00 (P < 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00. In liver, L-DOPA did not affect the rhythmicity and expression of these clock genes (P > 0.05). In addition, the cortisol secretion was increased (P > 0.05), but melatonin was further inhibited after L-DOPA treatment at 6:00 (P < 0.01).

Conclusions: In the circadian system of advanced PD rat models, circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.
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http://dx.doi.org/10.4103/0366-6999.204920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421180PMC
May 2017

Droplet-Based Multivolume Digital Polymerase Chain Reaction by a Surface-Assisted Multifactor Fluid Segmentation Approach.

Anal Chem 2017 01 13;89(1):822-829. Epub 2016 Dec 13.

Institute of Microanalytical Systems, Department of Chemistry and Innovation Center for Cell Signaling Network, Zhejiang University , Hangzhou, 310058, China.

Here we developed the surface-assisted multifactor fluid segmentation (SAMFS), an automated, fast, and flexible approach for generating a two-dimensional droplet array with tunable droplet volumes, for multivolume digital polymerase chain reaction (PCR). The SAMFS was developed based on the combination of robotic liquid handling and surface-assisted droplet generation techniques, where a continuous aqueous stream that flowed out from a capillary probe was segmented and immobilized on hydrophilic micropillars of a microchip into massive oil-covered droplets with the probe rapidly scanning over the microchip. We studied various factors affecting the droplet generation process, including micropillar top area, distance between adjacent micropillars, aqueous stream flow rate, and microchip moving speed, and demonstrated a high droplet generation throughput up to 50 droplets/s and a largest droplet volume adjusting range from 0.25 to 350 nL. The SAMFS approach was adopted to form an oil-covered array of 994 droplets with four different volumes (1.2, 6, 30, and 150 nL droplets) required for multivolume digital PCR within 8 min. The droplet array system was applied in absolute quantification of plasmid DNA under the multivolume digital PCR mode with a dynamic range spanning 4 orders of magnitude, as well as measurement of HER2 expression levels in different breast cancer cell lines. The results are consistent to those obtained by quantitative real-time PCR method, while the present one has higher precision.
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http://dx.doi.org/10.1021/acs.analchem.6b03687DOI Listing
January 2017

Arbuscular mycorrhizal fungi enhance soil carbon sequestration in the coalfields, northwest China.

Sci Rep 2016 10 17;6:34336. Epub 2016 Oct 17.

State Key Laboratory of Coal Resources and Safe Mining, China University of Mining and Technology (Beijing), Beijing 100083, China.

Carbon storage is affected by photosynthesis (P) and soil respiration (R), which have been studied extensively in natural and agricultural systems. However, the effects of P and R on carbon storages in the presence of arbuscular mycorrhizal fungi (AMF) in coalfields remain unclear. A field experiment was established in 2014 in Shendong coal mining subsidence area. The treatments comprised two inoculation levels (inoculated with or without 100 g AMF inoculums per seedlings) and four plant species [wild cherry (Prunus discadenia Koebne L.), cerasus humilis (Prunus dictyneura Diels L.), shiny leaf Yellow horn (Xanthoceras sorbifolium Bunge L.) and apricot (Armeniaca sibirica L.)]. AMF increased P of four species ranging from 15.3% to 33.1% and carbon storage, averaged by 17.2% compared to controls. Soil organic carbon (OC), easily extractable glomalin-relation soil protein (EE-GRSP), and total glomalin-relation soil protein (T-GRSP) were significantly increased by AMF treatment. The effect of AMF on the sensitivity of R depended on soil temperature. The results highlighted the exponential models to explain the responses of R to soil temperature, and for the first time quantified AMF caused carbon sequestration and R. Thus, to our knowledge, AMF is beneficial to ecosystems through facilitating carbon conservation in coalfield soils.
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http://dx.doi.org/10.1038/srep34336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066245PMC
October 2016

Study on the molecular mechanism of antinociception induced by ghrelin in acute pain in mice.

Peptides 2016 09 26;83:1-7. Epub 2016 Jul 26.

Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China. Electronic address:

Ghrelin has been identified as the endogenous ligand for the GHS-R1α (growth hormone secretagogue receptor 1 alpha). Our previous experiments have indicated that ghrelin (i.c.v.) induces antinociceptive effects in acute pain in mice, and the effects were mediated through the central opioid receptors and GHS-R1α. However, which opioid receptor (OR) mediates the antinociceptive effects and the molecular mechanisms are also needed to be further explored. In the present study, the antinociceptive effects of ghrelin (i.c.v.) could be fully antagonized by δ-opioid receptor antagonist NTI. Furthermore, the mRNA and protein levels of δ-opioid peptide PENK and δ-opioid receptor OPRD were increased after i.c.v injection of ghrelin. Thus, it showed that the antinociception of ghrelin was correlated with the GHS-R1α and δ-opioid receptors. To explore which receptor was firstly activated by ghrelin, GHS-R1α antagonist [D-Lys(3)]-GHRP-6 was co-injection (i.c.v.) with deltorphin II (selective δ-opioid receptor agonist). Finally, the antinociception induced by deltorphin II wasn't blocked by the co-injection (i.c.v.) of [D-Lys(3)]-GHRP-6, indicating that the GHS-R1α isn't on the backward position of δ-opioid receptor. The results suggested that i.c.v. injection of ghrelin initially activated the GHS-R1α, which in turn increased the release of endogenous PENK to activation of OPRD to produce antinociception.
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http://dx.doi.org/10.1016/j.peptides.2016.07.006DOI Listing
September 2016

FMRP-Mediated Axonal Delivery of miR-181d Regulates Axon Elongation by Locally Targeting Map1b and Calm1.

Cell Rep 2015 Dec 17;13(12):2794-807. Epub 2015 Dec 17.

State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China. Electronic address:

Subcellular targeting and local translation of mRNAs are critical for axon development. However, the precise local control of mRNA translation requires investigation. We report that the Fmr1-encoded protein, FMRP-mediated axonal delivery of miR-181d negatively regulates axon elongation by locally targeting the transcripts of MAP1B (Map1b) and calmodulin (Calm1) in primary sensory neurons. miR-181d affected the local synthesis of MAP1B and calmodulin in axons. FMRP was associated with miR-181d, Map1b, and Calm1. Both FMRP deficiency in Fmr1(I304N) mice and Fmr1 knockdown impeded the axonal delivery of miR-181d, Map1b, and Calm1 and reduced the protein levels of MAP1B and calmodulin in axons. Furthermore, nerve growth factor (NGF) induced Map1b and Calm1 release from FMRP and miR-181d-repressing granules, thereby promoting axon elongation. Both miR-181d overexpression and FMRP knockdown impaired NGF-induced axon elongation. Our study reveals a mechanism for the local regulation of translation by miR-181d and FMRP during axon development.
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http://dx.doi.org/10.1016/j.celrep.2015.11.057DOI Listing
December 2015

Green Tea Polyphenols Protects Cochlear Hair Cells from Ototoxicity by Inhibiting Notch Signalling.

Neurochem Res 2015 Jun 21;40(6):1211-9. Epub 2015 Apr 21.

Department of Otolaryngology-Head and Neck Surgery, Qianfo Shan Hospital Affiliated to Shandong University, Jinan, 250014, People's Republic of China.

Notch signalling pathway plays an essential role in the development of cochlea, which inhibits the proliferation of hair cells. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea, which presents strong antioxidant activation and has been applied for anti-cancer and anti-inflammatory. In this study, we treated the cochlear explant cultures with EGCG and found that EGCG can protect cochlear hair cells from ototoxic drug gentamicin. We demonstrated that EGCG could down-regulate the expression of Notch signalling pathway target genes, such as Hes1, Hes5, Hey1 and Hey5. However, the Notch pathway ligands such as Delta1, Jag1 and Jag2 were not affected by EGCG. To further illustrate the mechanism of recover cochlear hair cells, we demonstrated that EGCG inhibited the activity of γ-secrectase to suppress Notch signalling pathway and promoted the proliferation and regeneration of hair cells in the damaged cochlea. Our results suggest for the first time the role of EGCG as an inhibitor of the Notch signalling pathway, and support its potential value in hearing-impaired recovery in clinical therapy.
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http://dx.doi.org/10.1007/s11064-015-1584-3DOI Listing
June 2015

Printing 2-dimentional droplet array for single-cell reverse transcription quantitative PCR assay with a microfluidic robot.

Sci Rep 2015 Apr 1;5:9551. Epub 2015 Apr 1.

Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou, 310058, China.

This paper describes a nanoliter droplet array-based single-cell reverse transcription quantitative PCR (RT-qPCR) assay method for quantifying gene expression in individual cells. By sequentially printing nanoliter-scale droplets on microchip using a microfluidic robot, all liquid-handling operations including cell encapsulation, lysis, reverse transcription, and quantitative PCR with real-time fluorescence detection, can be automatically achieved. The inhibition effect of cell suspension buffer on RT-PCR assay was comprehensively studied to achieve high-sensitivity gene quantification. The present system was applied in the quantitative measurement of expression level of mir-122 in single Huh-7 cells. A wide distribution of mir-122 expression in single cells from 3061 copies/cell to 79998 copies/cell was observed, showing a high level of cell heterogeneity. With the advantages of full-automation in liquid-handling, simple system structure, and flexibility in achieving multi-step operations, the present method provides a novel liquid-handling mode for single cell gene expression analysis, and has significant potentials in transcriptional identification and rare cell analysis.
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http://dx.doi.org/10.1038/srep09551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381353PMC
April 2015

Semaphorin 3A activates the guanosine triphosphatase Rab5 to promote growth cone collapse and organize callosal axon projections.

Sci Signal 2014 Aug 26;7(340):ra81. Epub 2014 Aug 26.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.

Axon guidance (pathfinding) wires the brain during development and is regulated by various attractive and repulsive cues. Semaphorin 3A (Sema3A) is a repulsive cue, inducing the collapse of axon growth cones. In the mammalian forebrain, the corpus callosum is the major commissure that transmits information flow between the two hemispheres, and contralateral axons assemble into well-defined tracts. We found that the patterning of callosal axon projections in rodent layer II and III (L2/3) cortical neurons in response to Sema3A was mediated by the activation of Rab5, a small guanosine triphosphatase (GTPase) that mediates endocytosis, through the membrane fusion protein Rabaptin-5 and the Rab5 guanine nucleotide exchange factor (GEF) Rabex-5. Rabaptin-5 bound directly to Plexin-A1 in the Sema3A receptor complex [an obligate heterodimer formed by Plexin-A1 and neuropilin 1 (NP1)]; Sema3A enhanced this interaction in cultured neurons. Rabaptin-5 bridged the interaction between Rab5 and Plexin-A1. Sema3A stimulated endocytosis from the cell surface of callosal axon growth cones. In utero electroporation to reduce Rab5 or Rabaptin-5 impaired axon fasciculation or caused mistargeting of L2/3 callosal projections in rats. Overexpression of Rabaptin-5 or Rab5 rescued the defective callosal axon fasciculation or mistargeting of callosal axons caused by the loss of Sema3A-Plexin-A1 signaling in rats expressing dominant-negative Plexin-A1 or in NP1-deficient mice. Thus, our findings suggest that Rab5, its effector Rabaptin-5, and its regulator Rabex-5 mediate Sema3A-induced axon guidance during brain development.
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http://dx.doi.org/10.1126/scisignal.2005334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659511PMC
August 2014
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