Publications by authors named "Shiyu Feng"

60 Publications

Pro-inflammatory and proliferative microglia drive progression of glioblastoma.

Cell Rep 2021 Sep;36(11):109718

Department of Neurosurgery, The First Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China. Electronic address:

Scant understanding of the glioblastoma microenvironment and molecular bases hampers development of efficient treatment strategies. Analyses of gene signatures of human gliomas demonstrate that the SETD2 mutation is correlated with poor prognosis of IDH1/2 wild-type (IDH-WT) adult glioblastoma patients. To better understand the crosstalk between SETD2 mutant (SETD2-mut) glioblastoma cells and the tumor microenvironment, we leverage single-cell transcriptomics to comprehensively map cellular populations in glioblastoma. In this study, we identify a specific subtype of high-grade glioma-associated microglia (HGG-AM). Further analysis shows that transforming growth factor (TGF)-β1 derived from SETD2-mut/IDH-WT tumor cells activates HGG-AM, exhibiting pro-inflammation and proliferation signatures. Particularly, HGG-AM secretes interleukin (IL)-1β via the apolipoprotein E (ApoE)-mediated NLRP1 inflammasome, thereby promoting tumor progression. HGG-AM present extensive proliferation and infiltration to supplement the activated microglia pool. Notably, TGF-β1/TβRI depletion dramatically reduces HGG-AM density and suppresses tumor growth. Altogether, our studies identify a specific microglia subpopulation and establish the cellular basis of interactions between HGG-AM and glioblastoma cells.
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http://dx.doi.org/10.1016/j.celrep.2021.109718DOI Listing
September 2021

Altered microstructural pattern of white matter in Cushing's disease identified by automated fiber quantification.

Neuroimage Clin 2021 24;31:102770. Epub 2021 Jul 24.

Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, PR China. Electronic address:

A growing body of evidence suggests that altered brain structure plays a crucial role in the pathogenesis of neuropsychological abnormalities induced by hypercortisolism in patients with Cushing's disease. While most studies mainly focus on gray matter, white matter structure has been largely overlooked. In the current study, we conducted a cross-sectional diffusion tensor imaging study on 58 patients with Cushing's disease and 54 matched healthy individuals to profile the microstructural pattern using automated fiber quantification and investigate its association with neuroendocrine and neuropsychological deficits. The study revealed that microstructural pattern showed a widespread mean diffusivity, radial diffusivity increase, fractional anisotropy decrease and partial axial diffusivity increase among tracts notably in corpus callosum forceps, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus and arcuate fasciculus, while within the same tract abnormalities localized to specific positions. Moreover, compromised microstructural pattern of white matter in specific tracts and locations along the trajectory were associated with ACTH and cortisol concentration and cognitive decline in patients with Cushing's disease. Collectively, our study elucidates the form of white matter pathology induced by hypercortisolism and its association with cognitive decline which may provide further targets for early identification and intervention of Cushing's disease.
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http://dx.doi.org/10.1016/j.nicl.2021.102770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339293PMC
September 2021

Gas-liquid mass transfer characteristics of aviation fuel scrubbing in an aircraft fuel tank.

Sci Rep 2021 Jul 29;11(1):15426. Epub 2021 Jul 29.

College of Mechanical and Electrical Engineering, Xi'an Polytechnic University, Xi'an, China.

Dissolved oxygen evolving from aviation fuel leads to an increase in the oxygen concentration in an inert aircraft fuel tank ullage that may increase the flammability of the tank. Aviation fuel scrubbing with nitrogen-enriched air (NEA) can largely reduce the amount of dissolved oxygen and counteract the adverse effect of oxygen evolution. The gas-liquid mass transfer characteristics of aviation fuel scrubbing are investigated using the computational fluid dynamics method, which is verified experimentally. The effects of the NEA bubble diameter, NEA superficial velocity and fuel load on oxygen transfer between NEA and aviation fuel are discussed. Findings from this work indicate that the descent rate of the average dissolved oxygen concentration, gas holdup distribution and volumetric mass transfer coefficient increase with increasing NEA superficial velocity but decrease with increasing bubble diameter and fuel load. When the bubble diameter varies from 1 to 4 mm, the maximum change of descent rate of dissolved oxygen concentration is 18.46%, the gas holdup is 8.73%, the oxygen volumetric mass transfer coefficient is 81.45%. When the NEA superficial velocities varies from 0.04 to 0.10 m/s, the maximum change of descent rate of dissolved oxygen concentration is 146.77%, the gas holdup is 77.14%, the oxygen volumetric mass transfer coefficient is 175.38%. When the fuel load varies from 35 to 80%, the maximum change of descent rate of dissolved oxygen concentration is 21.15%, the gas holdup is 49.54%, the oxygen volumetric mass transfer coefficient is 44.57%. These results provide a better understanding of the gas and liquid mass transfer characteristics of aviation fuel scrubbing in aircraft fuel tanks and can promote the optimal design of fuel scrubbing inerting systems.
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http://dx.doi.org/10.1038/s41598-021-94786-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322315PMC
July 2021

The Association between Long-term Exposure to Ambient Air Pollution and Bone Strength in China.

J Clin Endocrinol Metab 2021 Jul 15. Epub 2021 Jul 15.

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.

Context: Evidence regarding the association of long-term exposure to air pollution on bone strength or osteoporosis is rare, especially in high polluted low- and middle-income countries. Little is known about whether the association between air pollution and bone strength changes at different bone strength distributions.

Objective: Using the baseline data from the China Multi-Ethnic Cohort, we investigated the association between long-term air pollution exposure and bone strength.

Methods: We used multiple linear models to estimate the association between air pollution and bone strength. And we conducted quantile regression models to investigate the variation of this association in the distribution of bone strength. The 3-year concentrations of PM1, PM2.5, PM10, and NO2 for each participant were assessed using spatial statistical models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound, with higher QUI values indicating greater bone strength.

Result: A total of 66,598 participants were included. Our analysis shows that every 10 μg/m 3 increase in 3-year average PM1, PM2.5, PM10, and NO2 was associated with -5.38 units (95% CI: -6.17, -4.60), -1.89 units (95% CI: -2.33, -1.44), -0.77 units (95% CI: -1.08, -0.47), and -2.02 units (95% CI: -2.32, -1.71) changes in the QUI, respectively. In addition, populations with higher bone strength may more susceptible to air pollution.

Conclusions: Long-term exposure to PM1, PM2.5, PM10, and NO2 was significantly associated with decreased bone strength in southwestern China adults. Air pollution exposure has a more substantial adverse effect on bones among populations with higher bone strength.
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http://dx.doi.org/10.1210/clinem/dgab462DOI Listing
July 2021

The chronic effect of cortisol on orchestrating cerebral blood flow and brain functional connectivity: evidence from Cushing's disease.

Metabolism 2021 02 14;115:154432. Epub 2020 Nov 14.

Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, Beijing, PR China. Electronic address:

Background: Cortisol has long been considered to play a crucial role in the pathogenesis of stress-related disorders. Cushing's disease (CD) provides an excellent "hyperexpression model" to investigate the chronic effects of cortisol on brain physiology and cognition. Previous studies have shown that cortisol is associated with neurophysiological alterations in animal models, which has also been examined by neural activity and cerebral blood flow (CBF) in human studies. However, the manner in which cortisol affects the coupling between brain activity and metabolic demand remains largely unknown.

Methods: Here we used functional magnetic resonance imaging and arterial-spin-labeling imaging to investigate neurophysiological coupling by examining the ratio of CBF and functional connectivity strength (FCS) in 100 participants (47 CD patients and 53 healthy controls).

Results: The results showed that CD was associated with lower CBF-FCS coupling predominantly in regions involving cognitive processing, such as the left dorsolateral prefrontal cortex and precuneus, as well as greater CBF-FCS coupling in subcortical structures, including the bilateral thalamus, right putamen, and hippocampus (P < 0.05, false discovery rate corrected). Moreover, regions with disrupted CBF-FCS coupling were associated with cortisol dosage and cognitive decline in CD patients.

Conclusions: Together, these findings elucidate the effect of cortisol excess on cerebral microenvironment regulation and associated cognitive disturbances in the human brain.
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http://dx.doi.org/10.1016/j.metabol.2020.154432DOI Listing
February 2021

Enhancing the Photovoltaic Performance of a Benzo[][1,2,5]thiadiazole-Based Polymer Donor via a Non-Fullerene Acceptor Pairing Strategy.

ACS Appl Mater Interfaces 2020 Nov 10;12(47):53021-53028. Epub 2020 Nov 10.

Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.

As a well-known electron-withdrawing group, benzo[][1,2,5]thiadiazole (BT) has been intensively studied and adopted to construct polymer donors with tunable band gaps. However, polymer solar cells (PSCs) with BT-based polymer donors, limited by the weak absorption and inflexible energy level of fullerene derivatives, usually suffer mediocre power conversion efficiencies (PCEs). Here, through subtly tailoring a BT unit with asymmetric fluoro and alkyloxy groups and judiciously pairing a BT-based polymer donor with three narrow band gap non-fullerene acceptors (e.g., IEICO-4F, ITOIC-2F, and IDTCN-O), active layers with complementary absorption spectra, small lowest unoccupied molecular orbital (LUMO) offsets, and preferred morphologies have been achieved. Consequently, PSCs with excellent values (over 20 mA/cm) and high PCEs up to 12.33% have been obtained. To the best of our knowledge, the value of 12.33% is among the highest PCEs for BT-based polymers in binary PSCs so far. This work demonstrates that the cooperative effect of energy levels, absorption spectra, and morphologies between the donors and acceptors is crucial for governing the performance of organic photovoltaics.
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http://dx.doi.org/10.1021/acsami.0c17571DOI Listing
November 2020

Combustion characteristics and typical pollutant emissions of corn stalk blending with municipal sewage sludge.

Environ Sci Pollut Res Int 2021 Feb 6;28(8):9792-9805. Epub 2020 Nov 6.

Engineering Research Centre of Oil Shale Comprehensive Utilization, Ministry of Education, School of Energy and Power Engineering, Northeast Electric Power University, Province, Jilin, 132012, Jilin, China.

The co-combustion of sewage sludge and biomass is a key problem in coal-fired power plants. The combustion characteristics and pollutant emissions of municipal sewage sludge and biomass could result in unpredictable operation and environmental problems. In this study, the combustion experiments of corn stalk (CS), municipal sewage sludge (SS), and their blends were conducted in the thermogravimetric analyzer and muffle furnace, focusing on the combustion characteristics and the pollutants (SO/NO) emissions with different temperature, proportion, and heating rate. It was found that the combustion characteristics of the mixture are affected by the mix ratio of SS. Compared with those of SS, the SO emission amount and S-SO conversion rate of CS are lower. The content of N in SS is higher than CS, but the conversion rate of N-NO is lower. Although the emissions of SO and NO from CS blending with SS are higher than those from CS combustion alone, the conversion rate of SO and NO decreases. This means that the co-combustion of CS and SS will reduce the content of pollutants released by CS combustion alone and effectively solve the environmental problems associated with CS incineration.
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http://dx.doi.org/10.1007/s11356-020-11463-yDOI Listing
February 2021

MSC-AS1 knockdown inhibits cell growth and temozolomide resistance by regulating miR-373-3p/CPEB4 axis in glioma through PI3K/Akt pathway.

Mol Cell Biochem 2021 Feb 26;476(2):699-713. Epub 2020 Oct 26.

Department of Neurosurgery, Chinese PLA General Hospital, No. 28, Fuxing Rd, Haidian District, Beijing, 100853, China.

Long non-coding RNAs (lncRNAs) have been widely reported to regulate the development and chemoresistance of a variety of tumors. Temozolomide (TMZ) is a first-line chemotherapy for treatment of glioma. However, the effect and the regulatory mechanism of lncRNA MSC-AS1 (MSC-AS1) in TMZ-resistant glioma remain unrevealed. Levels of MSC-AS1, microRNA-373-3p (miR-373-3p), and cytoplasmic polyadenylation element binding protein 4 (CPEB4) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). All protein expression was detected by western blot. Cell viability and the half maximal inhibitory concentration (IC) value of TMZ was assessed by cell counting kit-8 (CCK-8) assay. Cell cloning ability and apoptosis were examined by colony formation and flow cytometry assays, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the correlation between miR-373-3p and MSC-AS1 or CPEB4. The xenograft models were established to determine the effect of MSC-AS1 in vivo. MSC-AS1 was up-regulated in TMZ-resistant glioma tissues and cells, and glioma patients with high MSC-AS1 expression tend to have lower overall survival rate. MSC-AS1 suppression reduced the IC value of TMZ and proliferation, promoted apoptosis and TMZ sensitivity, and affected PI3K/Akt pathway in TMZ-resistant glioma cells. MSC-AS1 acted as miR-373-3p sponge, and miR-373-3p directly targeted CPEB4. Silencing miR-373-3p reversed the promoting effect of MSC-AS1 or CPEB4 knockdown on TMZ sensitivity. Furthermore, MSC-AS1 knockdown inhibited TMZ-resistant glioma growth in vivo by regulating miR-373-3p/CPEB4 axis through PI3K/Akt pathway. Collectively, MSC-AS1 knockdown suppressed cell growth and the chemoresistance of glioma cells to TMZ by regulating miR-373-3p/CPEB4 axis in vitro and in vivo through activating PI3K/Akt pathway.
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http://dx.doi.org/10.1007/s11010-020-03937-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873112PMC
February 2021

Efficient Ternary Organic Solar Cells with a New Electron Acceptor Based on 3,4-(2,2-Dihexylpropylenedioxy)thiophene.

ACS Appl Mater Interfaces 2020 Sep 27;12(36):40590-40598. Epub 2020 Aug 27.

Beijing Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Beijing Normal University, Beijing 100875, China.

In this work, a ternary blend strategy based on PBDB-T and two small molecular acceptors (IDTT-OB and ) is demonstrated to simultaneously improve the photocurrent and reduce the voltage loss in organic solar cells (OSCs). The improved photocurrent is partially due to a broad absorption spectrum of the active layer. In addition, we find that the ternary system possesses a higher degree of crystallinity, smaller domain size, higher domain purity, and higher and more balanced charge-carrier mobilities in comparison with the two corresponding binary systems. The reduced voltage loss in the ternary device is mainly due to a lower energy loss () of charge carriers. We achieve a of only 0.50 eV, which is one of the lowest values reported for the ternary nonfullerene OSCs. Our results have demonstrated that all photovoltaic parameters of ternary OSCs can be simultaneously improved by elaborately selecting the three active layer components.
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http://dx.doi.org/10.1021/acsami.0c11128DOI Listing
September 2020

Correlation of preoperative seizures with a wide range of tumor molecular markers in gliomas: An analysis of 442 glioma patients from China.

Epilepsy Res 2020 10 15;166:106430. Epub 2020 Jul 15.

Department of Neurosurgery, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China. Electronic address:

Purpose: Epileptic seizures often develop in 40-70 % of glioma patients and have a significant impact on patients' quality of life. Many biomarkers have been suggested to be associated with glioma-related preoperative seizures (GPS). The purpose of the present study was to investigate the possible correlation between GPS and clinicopathological factors and a wide range of glioma-associated molecular markers (GMMs).

Methods: First, a retrospective cohort study of 442 patients with glioma was evaluated at the PLA General Hospital. Univariate and multivariate logistic analyses were used to identify basic factors associated with GPS. Second, 40 pairs of cases who underwent deep sequencing of 68 GMMs were selected from both groups for in-depth analysis.

Results: Of the 442 patients examined in this study, 137 (31 %) had GPS. By analyzing the characteristics of these patients, the results showed that patient age (OR: 0.981, p = 0.037, 95 % CI: 0.964-0.999), WHO grade (OR: 0.678, p = 0.008, 95 % CI: 0.509-0.903) and IDH mutations (OR: 1.886, p = 0.013, 95 % CI: 1.143-3.11) in patients were associated with the occurrence of GPS. In our cohort, GPS did not differ by sex, tumor location, histopathological subtype, p53 expression, ARTX loss, MGMT gene promotor methylation, TERT promoter mutation, or 1p/19q co-deletion status. The results of the matching study showed that the paired groups had similar genetic expression profiles, and the mutation of these 68 GMMs was not correlated with the occurrence of GPS.

Conclusion: The current study updates existing information on GPS and genetic markers in gliomas and explores the correlation of a wide range of GMMs and GPS. These factors may provide insights for developing effective treatment strategies aimed at seizure control.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106430DOI Listing
October 2020

Organic Single-Crystal Transistor with Unique Photo Responses and Its Application as Light-Stimulated Synaptic Devices.

ACS Appl Mater Interfaces 2020 Jul 24;12(27):30627-30634. Epub 2020 Jun 24.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao West Road, Fuzhou, Fujian 350002, P. R. China.

Tremendous progress has been achieved on organic transistor-based photodetectors; however, because of the nonpositive correlation relationship between the photo/dark current ratio () and the gate voltage, the claimed best , (photoresponsivity), and * (detectivity) can hardly be obtained simultaneously at a given gate voltage, which severely compromises the device performance. Here, a light and voltage dually gated transistor based on an organic semiconducting single crystal of 2,6-dithienylanthracene (DTAnt) is developed. Attributing to its very low on/off ratio in the dark and the remarkable increment of mobilities under illumination, this phototransistor shows good performance with a of 3.83 × 10, of 1.32 A W, and * of 1.94 × 10 Jones achieved simultaneously at = -100 V. Besides, the good reversibility and repeatability of its light-responsive behavior allows for the construction of an artificial photonic neuromorphic device with demonstrated synaptic functions, including excitatory postsynaptic current, short/long-term memory , and pair-pulse facilitation/depression.
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http://dx.doi.org/10.1021/acsami.0c05809DOI Listing
July 2020

High Levels of HIST1H2BK in Low-Grade Glioma Predicts Poor Prognosis: A Study Using CGGA and TCGA Data.

Front Oncol 2020 8;10:627. Epub 2020 May 8.

Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, China.

A number of biomarkers have been identified for various cancers. However, biomarkers associated with glioma remain largely to be explored. In the current study, we investigated the relationship between the expression and prognostic value of the HIST1H2BK gene in glioma. Sequential data filtering (survival analysis, independent prognostic analysis, ROC curve analysis, and clinical correlation analysis) was performed, which resulted in identification of the association between the HIST1H2BK gene and glioma. Then, the HIST1H2BK gene was analyzed using bioinformatics (Kaplan-Meier survival analysis, univariate Cox analysis, multivariate Cox analysis, and ROC curve analysis). The results showed that low expression of HIST1H2BK was associated with better prognosis, and high expression of HIST1H2BK was associated with poor prognosis. In addition, HIST1H2BK was an independent prognostic indicator for patients with glioma. We also evaluated the association between HIST1H2BK and clinical characteristics. Furthermore, gene set enrichment analysis (GSEA) and analysis of immune infiltration were performed. The results showed that HIST1H2BK was associated with intensity of immune infiltration in glioma. Finally, co-expression analysis was performed. The results showed that HIST1H2BK was positively correlated with HIST1H2AG, HIST2H2AA4, HIST1H2BJ, HIST2H2BE, and HIST1H2AC, and negatively correlated with PDZD4, CRY2, GABBR1, rp5-1119a7.17, and KCNJ11. This study showed that upregulation of HIST1H2BK in low-grade glioma (LGG) tissue was an indicator of poor prognosis. Moreover, this study demonstrated that HIST1H2BK may be a promising biomarker for the treatment of LGG.
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http://dx.doi.org/10.3389/fonc.2020.00627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225299PMC
May 2020

Associations of histological and molecular alterations with invasion of the corpus callosum in gliomas.

Acta Neurochir (Wien) 2020 07 21;162(7):1691-1699. Epub 2020 May 21.

Department of Neurosurgery, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.

Background: Glioma invading the corpus callosum (CC) accounts for approximately 14% of gliomas and is thought to be more aggressive. However, there is still a lack of studies on the pathogenesis and molecular features of this condition. Here, we examined the occurrence association of CC invasion with respect to patients' clinical, pathological, and genetic characteristics.

Methods: First, a cohort of 331 patients was included, with 86 cases (26%) that were diagnosed with invasion glioma. They were all analyzed for basic clinical and pathological characteristics and four routinely tested glioma molecular markers. Second, 29 pairs of patients who underwent deep sequencing of 68 glioma molecular alterations were selected from both groups for in-depth analysis.

Results: The results of the first part showed that there was no difference between the two groups in terms of the basic factors in univariate analysis, while in multivariate logistic analysis, WHO grade was the risk factor for CC invasion (p = 0.001). The results of the second part showed that the paired groups had different genetic expression profiles, which highlighted glioma invading the CC as a distinct biological entity. PDGFRA mutation (PDGFRAmut) was present in 9 patients with invasive gliomas (31%), but only in one case (3.4%) in the control group (OR 17.331; 95% CI 1.987-151.156).

Conclusion: Our data revealed the clinical, pathological, and genetic characteristics of glioma invading the CC and showed that it may be associated with glioma WHO grade and PDGFRAmut, but not other factors. Thus, the risk signaling pathway may offer potential therapeutic targets for this disease.
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http://dx.doi.org/10.1007/s00701-020-04376-9DOI Listing
July 2020

Applications of cerebrospinal fluid circulating tumor DNA in the diagnosis of gliomas.

Jpn J Clin Oncol 2020 Mar;50(3):325-332

Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China.

Objective: The 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was revised to include molecular biomarkers as diagnostic criteria. However, conventional biopsies of gliomas were spatially and temporally limited. This study aimed to determine whether circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) could provide more comprehensive diagnostic information to gliomas.

Methods: Combined with clinical data, we analyzed gene alterations from CSF and tumor tissues of newly diagnosed patients, and detected mutations of ctDNA in recurrent patients. We simultaneously analyzed mutations of ctDNA in different glioma subtypes, and in lower-grade gliomas (LrGG) versus glioblastoma multiforme (GBM).

Results: CSF ctDNA mutations had high concordance rates with tumor DNA (tDNA). CSF ctDNA mutations of PTEN and TP53 were commonly detected in recurrent gliomas patients. IDH mutation was detected in most of CSF ctDNA derived from IDH-mutant diffuse astrocytomas, while CSF ctDNA mutations of RB1 and EGFR were found in IDH-wild-type GBM. IDH mutation was detected in LrGG, whereas Rb1 mutation was more commonly detected in GBM.

Conclusions: CSF ctDNA detection can be an alternative method as liquid biopsy in gliomas.
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http://dx.doi.org/10.1093/jjco/hyz156DOI Listing
March 2020

Differential long non-coding RNA (lncRNA) profiles associated with hippocampal sclerosis in human mesial temporal lobe epilepsy.

Int J Clin Exp Pathol 2019 1;12(1):259-266. Epub 2019 Jan 1.

Department of Neurosurgery, Chinese PLA General Hospital, Chinese PLA Postgraduate Medical School Beijing 100853, China.

Objective: The aim of this study was to analyze the expression profiles of long non-coding RNA (lncRNAs) in human mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and to detect the functions of lncRNAs in epileptogenesis in MTLE.

Materials And Methods: We used microarray analysis to analyze the differential expression of lncRNAs and mRNAs in three hippocampal sclerosis and three normal hippocampus samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the microarrray results. A coding and non-coding gene co-expression network was constructed based on the correlation between the differential expression of lncRNAs and mRNAs. Gene ontology (GO) and pathway analyses were then performed to determine the potential roles of the differentially expressed mRNAs in the co-expression network. Lastly, to understand potential functions of lncRNAs in MTLE, cis-/trans-acting lncRNAs were predicted using bioinformatic analysis.

Results: Compared with control hippocampus, 497 differentially expressed lncRNAs were identified in the hippocampal sclerosis samples, consisting of 294 up-regulated and 203 down-regulated lncRNAs (fold-change >2.0 or <-2.0, P<0.05). Similarly, 399 differentially expressed mRNAs were identified with 236 up-regulated and 163 down-regulated. There were 356 lncRNAs and 332 mRNAs in the non-coding and coding co-expression network, in which the highly enriched GO categories were related to the inflammatory response, and neuropeptide receptor activity. Nine pairs of lncRNAs and mRNAs (located within 10 kb of each other) were found to exert functional effects on epileptogenesis.

Conclusion: Differential expression of lncRNAs of varying length and location were observed in human MTLE with hippocampal sclerosis. The dysregulated lncRNAs with co-dysregulated mRNAs in inflammatory response and neuropeptide receptor activity categories are predicted to play roles in epileptogenesis in MTLE. LncRNA may contribute to epileptogenesis by targeting .
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944018PMC
January 2019

Regulating the Packing of Non-Fullerene Acceptors via Multiple Noncovalent Interactions for Enhancing the Performance of Organic Solar Cells.

ACS Appl Mater Interfaces 2020 Jan 15;12(4):4638-4648. Epub 2020 Jan 15.

Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Center for Advanced Quantum Studies, Department of Physics and Applied Optics, Beijing Area Major Laboratory , Beijing Normal University , Beijing 100875 , P. R. China.

Three noncovalently fused-ring electron acceptors (, , and ) are synthesized. Single crystals of and are prepared, and structure analyses reveal that the molecular backbone can be planarized via the formation of the intramolecular noncovalent interactions. These acceptor molecules can be packed closely in the solid state via π-π stacking and static interactions between the central phenylene unit and the terminal group with a distance of 3.3-3.4 Å. Besides, multiple intermolecular noncovalent interactions can be observed in the single crystal structure of the fluorinated acceptor , which help increase the crystallinity of acceptors and the charge mobility of the blends. Photovoltaic devices based on give a power conversion efficiency of 12.36%, higher than 12.08% for and 10.80% for .
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http://dx.doi.org/10.1021/acsami.9b18076DOI Listing
January 2020

Functional characterization of grass carp (Ctenopharyngodon idella) interleukin-2 in head kidney leukocytes.

Fish Shellfish Immunol 2020 Feb 25;97:500-508. Epub 2019 Dec 25.

Center for Informational Biology, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.

Interleukin (IL)-2 belongs to the four-helix bundle cytokine family and plays key roles in growth, survival, activation-induced cell death and differentiation of the immune cells. In cyprinid fish, only common carp interleukin-2 (il2) has been cloned because of relatively low sequence homology between carp Il-2 and its homologs in other fish species. In the present study, the coding sequence of grass carp Il-2 (gcIl-2) was cloned and its identity was verified via bioinformatic analysis. Tissue distribution study showed that grass carp il2 (gcil2) mRNA was expressed in thymus, head kidney and gill with relatively high levels. Recombinant gcIl-2 (rgcIl-2) protein was subsequently prepared by using a prokaryotic expression system followed by a refolding method. The purified rgcIl-2 displayed an ability to stimulate the cell proliferation along with an increased mRNA expression of cd4l but not cd8a, igm or mcsfr in grass carp head kidney leukocytes (HKLs), suggesting the possible involvement of gcIl-2 in T helper (Th) cell proliferation. In the same cell model, rgcIl-2 significantly enhanced mRNA expression of some cytotoxic molecules including perforin-like protein 2, granzyme B-like and Fas ligand, indicating the modulation of cytotoxic cells by gcIl-2 in grass carp HKLs. Besides, gene expression of regulatory T (Treg) cell- and Th1/2 cell-related cytokines or transcription factors was detected in grass carp HKLs treated by rgcIl-2. Results showed that rgcIL2 treatment increased the mRNA expression of foxp3, cd25l, ifng2, il12p35, tbet, tnfa, il2, il4/13a, il4/13b and gata3l in HKLs, implying the regulatory roles of Il-2 in the expression of these immune genes and its possible involvement in differentiation of Treg and Th1/2 cells. These observations together with the related studies in other fishes suggest the existence of cytotoxic cells, Treg and Th1/2 subpopulations in fish species and the functional roles of Il-2 in these cells.
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http://dx.doi.org/10.1016/j.fsi.2019.12.077DOI Listing
February 2020

Novel functions of grass carp three p40 isoforms as modulators of Th17 signature cytokine expression in head kidney leukocytes.

Fish Shellfish Immunol 2020 Mar 14;98:995-1000. Epub 2019 Nov 14.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.

Interleukin (IL)-12p40, a component of IL-12 and IL-23, can be secreted as monomer and homodimer in mammals. Our previous study has proved the existence of natural three p40 isoforms and their proinflammatory properties in grass carp. In the present study, we unexpectedly found that recombinant grass carp p40a/b/c (rgcp40a, rgcp40b and rgcp40c) were able to enhance the mRNA levels of grass carp il-17a/f1 (gcil-17a/f1) in a dose- and time-dependent manner in head kidney leukocytes (HKLs). In agreement with these findings, the enzyme-linked immunosorbent assay (ELISA) showed that rgcp40a, rgcp40b and rgcp40c markedly stimulated gcIl-17a/f1 secretion from the HKLs. Together with their stimulatory effects on grass carp gcil-22 and gcil-26 expression, our data suggested their potential to mediate Th17-like response in grass carp. To support this notion, we investigated the underlying mechanisms for the regulation of rgcp40 isoforms on gcil-17a/f1 expression, and found that three rgcp40 isoforms significantly induced the activation of Erk, Jnk and Stat3 pathways in a time-dependent oscillation in the same cell model. Moreover, three rgcp40 isoforms-induced gcil-17a/f1 mRNA expression was suppressed by the inhibition on Erk, Jnk and Stat3 pathways, suggesting the signaling pathways in the p40 isoforms-mediating il-17a/f1 transcription. These studies for the first time proved the involvement of three gcp40 isoforms in mediating Th17 signature cytokine expression in fish immune cells, therefore providing new insights into the roles of p40 in teleost immunity.
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http://dx.doi.org/10.1016/j.fsi.2019.11.025DOI Listing
March 2020

Necroptotic astrocytes contribute to maintaining stemness of disseminated medulloblastoma through CCL2 secretion.

Neuro Oncol 2020 05;22(5):625-638

Department of Neurosurgery, The First Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.

Background: Medulloblastoma (MB) with metastases at diagnosis and recurrence correlates with poor prognosis. Unfortunately, the molecular mechanism underlying metastases growth has received less attention than primary therapy-naïve MB. Though astrocytes have been frequently detected in brain tumors, their roles in regulating the stemness properties of MB stem-like cells (MBSCs) in disseminated lesions remain elusive.

Methods: Effects of tumor-associated astrocyte (TAA)-secreted chemokine C-C ligand 2 (CCL2) on MBSC self-renewal was determined by immunostaining analysis. Necroptosis of TAA was examined by measuring necrosome activity. Alterations in Notch signaling were examined after inhibition of CCL2. Progression of MBSC-derived tumors was evaluated after pharmaceutical blockage of necroptosis.

Results: TAA, as the essential components of disseminated tumor, produced high levels of CCL2 to shape the inflammation microenvironment, which stimulated the enrichment of MBSCs in disseminated MB. In particular, CCL2 played a pivotal role in maintaining stem-like properties via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3)-mediated activation of Notch signaling. Loss of CCL2/C-C chemokine receptor 2 (CCR2) function repressed the JAK2/STAT3-Notch pathway and impaired MBSC proliferation, leading to a dramatic reduction of stemness, tumorigenicity, and metastasizing capability. Furthermore, necroptosis-induced CCL2 release depended on activation of receptor-interacting protein 1 (RIP1)/RIP3/mixed lineage kinase domain-like pseudokinase (MLKL) in TAA, which promoted the oncogenic phenotype. Blockade of necroptosis resulted in CCL2 deprivation and compromised MBSC self-proliferation, indicating MBSCs outsourced CCL2 from necroptotic TAA. Finally, CCL2 was upregulated in high-risk stages of MB, further supporting its value as a prognostic indicator.

Conclusion: These findings highlighted the critical role of CCL2/CCR2 in Notch signaling activation in MBSCs and revealed a necroptosis-associated glial cytokine microenvironment driving stemness maintenance in disseminations.Key Points1. TAA-derived CCL2 promoted stemness in disseminated MBSCs through Notch signaling activation via the JAK2/STAT3 pathway.2. TAA released CCL2 in a RIP1/RIP3/MLKL-dependent manner leading to necroptosis.
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http://dx.doi.org/10.1093/neuonc/noz214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229261PMC
May 2020

Hypomethylation of 111 Probes Predicts Poor Prognosis for Glioblastoma.

Front Neurosci 2019 25;13:1137. Epub 2019 Oct 25.

National Engineering Laboratory for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, China.

Glioblastoma (GBM) is a complicated brain tumor with heterogeneous outcome. Identification of effective biomarkers is an urgent need for the treatment decision-making and precise evaluation of prognosis. Based on a relatively large dataset of genome-wide methylation (138 glioblastoma patients), a joint-score of 111 methyl-probes was found to be of statistical significance for prognostic evaluation. Low joint-score were significantly associated with adverse outcomes (OS: < 0.001, PFS: = 0.03). Multivariable analyses adjusted for known risk factors confirmed the low joint-score of 111 methyl-probes as a high risk factor. The prognostic value of the methylated joint-score was further validated in another dataset of glioblastoma patients (OS: = 0.006). Additionally, variance analysis revealed that aberrant genetic and epigenetic alterations were significantly associated with the joint-score of those methyl-probes. In conclusion, our results supported the joint-score of 111 methyl-probes as a potential prognosticator for the precision treatment of glioblastoma.
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http://dx.doi.org/10.3389/fnins.2019.01137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823878PMC
October 2019

Characterization of a new il-4/13 homologue in grass carp (Ctenopharyngodon idella) and its cooperation with M-CSF to promote macrophage proliferation.

Fish Shellfish Immunol 2019 Oct 26;93:508-516. Epub 2019 Jul 26.

Center for Informational Biology, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.

In this study, a new il-4/13 cDNA was isolated from grass carp (Ctenopharyngodon idella) using homologous cloning. The phylogenetic tree and sequence alignment of the deduced amino acid (aa) sequence showed that it was closer to grass carp il-4/13b (gcil-4/13b) than other homologues and therefore named gcil-4/13b-like (gcil-4/13bl). It has 399-nt coding sequence (CDS) which is less than gcil-4/13b (408 nt). In addition, the cloned gcil-4/13bl gene is approximately 1600 bp in length and has a conserved genetic structure consisting of four exons and three introns. Compared to gcil-4/13b gene, it has a variety of nucleotides variation across the CDS and contains a longer intron 3, suggesting that it is a new gcil-4/13 gene. The gcil-4/13bl transcripts were ubiquitously expressed in almost all selected tissues, and there was almost only gcil-4/13bl detected in brain and head kidney (HK). Recombinant grass carp (rgc) Il-4/13bl was prepared by using Escherichia coli (E. coli) Rosetta-gami 2 (DE3). The functional study demonstrated that rgcIl-4/13bl significantly upregulated arginase-2 gene expression and arginase activity, whilst downregulated nitric oxide (NO) production as well as the transcript levels of inducible nitric oxide synthesase (inos) and ifn-γ in freshly isolated grass carp HK monocytes/macrophages (M0/Mϕ). These data suggested that the newly cloned il-4/13bl had the conserved functions to activate M2-type but antagonize M1-type macrophages. Furthermore, rgcIl-4/13bl was able to drive the proliferation of M0/Mϕ which were pre-treated by rgcM-csf, indicating the involvement of gcIl-4/13bl in the proliferation of macrophages. Here we not only identified a new il-4/13-encoding gene in grass carp, but also for the first time revealed a novel function of fish Il-4/13 combined with M-csf engaging in M0/Mϕ proliferation.
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http://dx.doi.org/10.1016/j.fsi.2019.07.070DOI Listing
October 2019

Noncovalently fused-ring electron acceptors with near-infrared absorption for high-performance organic solar cells.

Nat Commun 2019 Jul 10;10(1):3038. Epub 2019 Jul 10.

Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Beijing Normal University, 100875, Beijing, China.

Non-fullerene fused-ring electron acceptors boost the power conversion efficiency of organic solar cells, but they suffer from high synthetic cost and low yield. Here, we show a series of low-cost noncovalently fused-ring electron acceptors, which consist of a ladder-like core locked by noncovalent sulfur-oxygen interactions and flanked by two dicyanoindanone electron-withdrawing groups. Compared with that of similar but unfused acceptor, the presence of ladder-like structure markedly broadens the absorption to the near-infrared region. In addition, the use of intramolecular noncovalent interactions avoids the tedious synthesis of covalently fused-ring structures and markedly lowers the synthetic cost. The optimized solar cells displayed an outstanding efficiency of 13.24%. More importantly, solar cells based on these acceptors demonstrate very low non-radiative energy losses. This research demonstrates that low-cost noncovalently fused-ring electron acceptors are promising to achieve high-efficiency organic solar cells.
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http://dx.doi.org/10.1038/s41467-019-11001-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620284PMC
July 2019

Functional characterization of three fish-specific interleukin-23 isoforms as regulators of Th17 signature cytokine expression in grass carp head kidney leukocytes.

Fish Shellfish Immunol 2019 Sep 13;92:315-321. Epub 2019 Jun 13.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. Electronic address:

Mammalian Interleukin (IL)-23 is a heterodimeric cytokine with an IL-23-specific P19 subunit and a P40 subunit shared with IL-12, and plays a key role in the regulation of cell differentiation as well as inflammation. We previously demonstrated the existence of three soluble fish Interleukin (Il)-23 isoforms consist of a single P19 and one of three P40 isoforms (P40a/b/c) in grass carp. In the present study, three recombinant grass carp Il-23 (rgcIl-23) isoforms were prepared by linking gcP19 and gcP40a/b/c in a prokaryotic expression system, and then their functional properties were verified in grass carp head kidney leukocytes (HKLs). All three rgcIl-23 isoforms showed the bioactivities to divergently upregulate the mRNA expression of Th17 signature cytokines (il17a/f1, il21, il22 and il26) as well as Il-23 receptor (il23r) in HKLs. Moreover, they also promoted gcIl-17a/f1 secretion in a dose-dependent manner, strengthening their roles in Th17-like response. Furthermore, induction of il17a/f1 and il23r transcription by rgcIl-23 was blocked by a STAT3 inhibitor in grass carp HKLs, suggesting the involvement of STAT3 signaling in these inductions. Taken together, we for the first time identified the bioactivities of fish Il-23 isoforms and particularly revealed the existence of Il-23/Il-17a/f1 axis in fish, thereby advancing our understanding of Th17-like responses in fish immunity.
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http://dx.doi.org/10.1016/j.fsi.2019.06.028DOI Listing
September 2019

Dysregulation of resting-state functional connectivity in patients with Cushing's disease.

Neuroradiology 2019 Aug 17;61(8):911-920. Epub 2019 May 17.

Department of Neurosurgery, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.

Purpose: To explore the anatomical distance-dependent functional connectivity patterns in patients with active phase of Cushing's disease (CD) and to evaluate the associations between hypercortisol exposure and regional normalized functional connectivity strengths (nFCSs).

Methods: Based on the fMRI data in 32 CD patients and 32 healthy controls (HCs), we computed the nFCSs for each voxel in the brain and further divided them into long-range and short-range nFCSs. General linear models was used to investigate between-group differences in these nFCS metrics and the correlations between the nFCSs and clinical variables.

Results: Compared with HC, CD patients showed dysregulation of the nFCSs mainly in the default mode network. They showed an overall higher nFCS in bilateral parahippocampal cortex mainly owing to the disruption of long-range nFCS and a relatively lower nFCS in bilateral posterior cingulate cortex (PCC), bilateral lateral parietal cortex (LP), and right prefrontal cortex (PFC). In addition, their long-range nFCS was lower in the bilateral anterior cingulate cortex, PCC, and LP; short-range nFCS was lower in the bilateral PFC. Notably, the positive correlation between the nFCSs in their right parahippocampal cortex and serum cortisol levels at 08:00 remained significant after taking the anatomical distance into consideration.

Conclusion: The discrepant functional connectivity patterns found in our study indicated a hypercortisol-associated, distance-dependent disruption of resting-state functional connectivity in patients with active CD. We provide novel insights into the impacts of hypercortisol exposure and the pathophysiologic mechanisms of CD, which may facilitate advances in CD intervention ultimately.
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http://dx.doi.org/10.1007/s00234-019-02223-yDOI Listing
August 2019

Production and functional insights into the potential regulation of three isoforms of grass carp p40 subunit in inflammation.

Fish Shellfish Immunol 2019 Jun 10;89:403-410. Epub 2019 Apr 10.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. Electronic address:

The p40 subunit is known as a component of Interleukin (IL)-12 and IL-23. In mammals, p40 can be secreted as a monomer or homodimer and acts independently to mediate cellular responses. Recently, three p40 paralogues were isolated and identified from grass carp and other fish species, but whether they exist independently as well as their functional consequences and significance remain unclear. In the present study, using grass carp as the model, we for the first time demonstrated the existence of natural fish p40a, p40b and p40c (gcp40a, gcp40b and gcp40c) mainly as a monomer in culture supernatant of head kidney leukocytes (HKLs). Particularly, their excessive secretion induced by various immune stimuli suggests possible involvement of free p40s in fish immune responses. To define their functions, recombinant grass carp p40a/b/c (rgcp40a, rgcp40b and rgcp40c) were prepared by Pichia pastoris expression system, and they possessed the activities to enhance the secretion of pro-inflammatory cytokines including Il-1β and tumor necrosis factor-α (Tnf-α) in grass carp HKLs. These pro-inflammatory properties of p40 isoforms prompted us to investigate their roles during the inflammatory process. In line with this, in vivo study revealed the pathogenic effect of rgcp40a on intestinal inflammation, whereas gcp40a polyclonal antibodies remarkably ameliorated Aeromonas hydrophila-induced intestinal histopathological changes. Taken together, our results uncover the biological significance of free p40s in teleost, and provide new clue for targeting fish intestinal inflammation.
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http://dx.doi.org/10.1016/j.fsi.2019.04.015DOI Listing
June 2019

Endocrinological Outcomes of Intraoperative MRI-Guided Endoscopic Transsphenoidal Surgery for Non-Functioning Pituitary Adenoma.

Turk Neurosurg 2019 ;29(5):635-642

Chinese PLA General Hospital, Department of Neurosurgery, Beijing, China.

Aim: To assess the endocrinological outcomes of high-field (1.5-T) intraoperative magnetic resonance imaging (iMRI)-guided endoscopic transsphenoidal surgery (TSS) for non-functioning pituitary adenomas (NFPAs).

Material And Methods: Radiological and endocrinological data were retrospectively collected and analyzed for 133 consecutive patients who underwent iMRI-guided endoscopic TSS for NFPA.

Results: Between the first and final scans, the gross total resection (GTR) rate increased from 42.9% to 63.9%. Preoperatively, 105 patients were deficient in at least 1 pituitary hormone axis (corticotroph axis: 51 patients, gonadotrope axis: 89 patients, thyrotrope axis: 51 patients, growth hormone axis: 19 patients). After surgery, varying rates of improvement were observed in patients with deficiencies in the growth hormone (89.5%), corticotroph (78.4%), gonadotrope (49.4%), and thyrotrope axes (33.3%). Pituitary function deteriorated in 75 patients (corticotroph axis: 23 patients, gonadotrope axis: 30, thyrotrope axis: 56 patients). Univariate logistic regression analyses revealed that, among patients with hypopituitarism of the gonadotrope axis, women were more likely than men to experience recovery (odds ratio [OR]: 0.417, 95% confidence interval [CI]: 0.191-0.913; p=0.029) and not experience deterioration (OR: 2.539, 95% CI: 1.057-6.098; p=0.037). The increased GTR rate, based on the iMRI findings, was not associated with an increased incidence of postoperative hypopituitarism or lower recovery rates in the pituitary axes (both p > 0.05).

Conclusion: The GTR rate for NFPAs was increased using iMRI, although this increase was not associated with improvement or deterioration of hypopituitarism.
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http://dx.doi.org/10.5137/1019-5149.JTN.22603-18.2DOI Listing
December 2019

Controlling Molecular Packing and Orientation via Constructing a Ladder-Type Electron Acceptor with Asymmetric Substituents for Thick-Film Nonfullerene Solar Cells.

ACS Appl Mater Interfaces 2019 Jan 9;11(3):3098-3106. Epub 2019 Jan 9.

Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry , Beijing Normal University , Beijing 100875 , China.

A nonfullerene acceptor, IDTT-OB, employing indacenodithieno[3,2- b]thiophene (IDTT) decorated with asymmetric substituents as the core, is designedly prepared. In comparison with the analogue IDT-OB, extending the five-heterocyclic indacenodithiophene (IDT) core to seven-heterocyclic fused ring endows IDTT-OB with more broad absorption and elevated highest occupied molecular orbital energy level. In addition, IDTT-OB shows a more intense molecular packing and a higher crystalline behavior with a strong face-on orientation in the neat film and the PBDB-T:IDTT-OB blend film. Furthermore, an ideal nanomorphology with a domain size of 19 nm can be obtained, which is in favor of exciton diffusion and charge separation. Accordingly, PBDB-T:IDTT-OB-based polymer solar cells demonstrate a maximum power conversion efficiency (PCE) of 11.19% with an impressive fill factor of 0.74, comparable to the state-of-the-art acceptors with similar molecular backbones. More importantly, IDTT-OB-based devices show good tolerance to the film thickness, which maintain a high PCE of 10.20% with a 250 nm thick active layer, demonstrating that the asymmetric acceptor is profound for fabricating high-efficiency thick-film nonfullerene solar cells.
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http://dx.doi.org/10.1021/acsami.8b19596DOI Listing
January 2019

Identification and functional characterization of grass carp (Ctenopharyngodon idella) tumor necrosis factor receptor 2 and its soluble form with potentiality for targeting inflammation.

Fish Shellfish Immunol 2019 Mar 28;86:393-402. Epub 2018 Nov 28.

School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, PR China. Electronic address:

Tumor necrosis factor-alpha (TNF-α) signals through two distinct cell surface receptors, TNFR1 and TNFR2 in mammals. In the present study, grass carp Tnfr2 (gcTnfr2) was isolated and characterized. Sequence alignment and phylogenetic analysis suggested that gcTnfr2 was a homolog of goldfish and zebrafish Tnfr2. Tissue distribution assay showed gctnfr2 transcripts were expressed in all examined tissues similar to gctnfr1. To functionally characterize the newly cloned molecule, gcTnfr2 was overexpressed in COS7 cell lines and it showed the ability to mediate the recombinant grass carp Tnf (rgcTnf)-α-triggered NF-κΒ activity and gcil1b promoter activity, clarifying its role in mediating Tnf-α signaling. The recombinant soluble form of gcTnfr2 (rgcsTnfr2) was prepared and it was able to interact with rgcTnf-α with higher affinity than that of rgcsTnfr1. Moreover, grass carp soluble Tnfr2 (gcsTnfr2) were detected in the culture medium of grass carp head kidney leukocytes (HKLs) and heat-inactivated A. hydrophila challenge significantly induced its production, indicating involvement of gcsTnfr2 in inflammation response. In agreement with this notion, rgcsTnfr2 effectively antagonized the effect of rgcTnf-α on il1b mRNA expression in HKLs, suggesting anti-Tnf-α property of gcsTnfr2. To strengthen the anti-inflammatory role of soluble Tnfr2, bacteria were injected intraperitoneally in grass carp followed by rgcsTnfr2. Hematoxylin-eosin (HE) staining of head kidney, spleen and intestine showed that rgcsTnfr2 could significantly improve infection-induced histopathological changes. These results functionally identified gcTnfr2 and its soluble form, particularly highlighting the role of gcsTnfr2 against Tnf-α-triggered inflammatory signaling. In this line, rgcsTnfr2 displayed anti-inflammatory potentiality during infection, thereby providing a powerful mediator of inflammation control in fish.
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http://dx.doi.org/10.1016/j.fsi.2018.11.061DOI Listing
March 2019

MicroRNA-142-3p inhibits proliferation and induces apoptosis by targeting the high-mobility group box 1 via the Wnt/β-catenin signaling pathway in glioma.

Int J Clin Exp Pathol 2018 1;11(9):4493-4502. Epub 2018 Sep 1.

Department of Neurosurgery, Chinese PLA General Hospital Beijing, China.

Background: Glioma is one of the most common brain tumors. Copious microRNAs have been identified as critical regulators in the development of glioma. MicroRNA-142-3p (miR-142-3p) has been reported as a tumor suppressor in some malignancies. However, the roles and molecular mechanisms of miR-142-3p in the development of glioma are poorly defined.

Methods: An RT-qPCR assay was carried out to detect expressions of miR-142-3p and high-mobility group box 1 (HMGB1) mRNA. A bioinformatic analysis and a luciferase reporter assay were used to explore the interaction between miR-142-3p and HMGB1 3'UTR. A Western blot assay was performed to examine protein expression of HMGB1, c-myc, cleaved caspase-3, and β-catenin. Cell proliferative ability was assessed by an MTS assay. The cell apoptotic rate was measured using flow cytometry via the double-staining of Annexin V-FITC and propidium iodide (PI).

Results: MiR-142-3p expression was remarkably reduced in glioma tissues. Mechanical analyses showed that HMGB1 was a target of miR-142-3p. Functional investigations revealed that miR-142-3p suppressed proliferation and induced apoptosis by targeting HMGB1 in glioma cells. Moreover, miR-142-3p inactivated Wnt/β-catenin signaling and activated caspase-3 signaling by targeting HMGB1 in glioma cells.

Conclusion: MiR-142-3p inhibits proliferation and induces apoptosis by targeting HMGB1 via the Wnt/β-catenin signaling pathway in glioma cells, providing a deep exploration into the roles and molecular basis of miR-142-3p in the proliferation and apoptosis of glioma cells and highlighting the therapeutical values of miR-142-3p and HMGB1 for glioma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962963PMC
September 2018

Functional characterization of grass carp runt-related transcription factor 3: Involvement in TGF-β1-mediated c-Myc transcription in fish cells.

Fish Shellfish Immunol 2018 Nov 10;82:130-135. Epub 2018 Aug 10.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China. Electronic address:

In mammals, both runt-related transcription factor 3 (RUNX3) and c-Myc are the downstream effectors of transforming growth factor-β1 (TGF-β1) signaling to mediate various cellular responses. However, information of their interaction especially in fish is lacking. In the present study, grass carp (Ctenopharyngodon idella) runx3 (gcrunx3) cDNA was cloned and identified. Interestingly, opposing effects of recombinant grass carp TGF-β1 (rgcTGF-β1) on c-myc and runx3 mRNA expression were observed in grass carp periphery blood lymphocytes (PBLs). Parallelly, Runx3 protein levels were enhanced by rgcTGF-β1 in the cells. These findings prompted us to examine whether Runx3 can mediate the inhibition of TGF-β1 on c-myc expression in fish cells. In line with this, overexpression of grass carp Runx3 and Runx3 DN (a dominant-negative form of Runx3) in grass carp kidney cell line (CIK) cells decreased and increased c-myc transcript levels, respectively. Particularly, the regulation of Runx3 and Runx3 DN on c-myc mRNA expression was direct since they were presented in the nucleus without any stimulation. In addition, rgcTGF-β1 alone suppressed c-myc mRNA expression in CIK cells as in PBLs. Moreover, this inhibitory effect was also observed when grass carp Runx3 and Runx3 DN were overexpressed. These results strengthened the role of TGF-β1 signaling in controlling c-myc transcription. Taken together, TGF-β1-mediated c-myc expression was affected at least in part by Runx3, thereby firstly exploring the functional role of Runx3 in TGF-β1 down-regulation on c-myc mRNA expression in fish.
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http://dx.doi.org/10.1016/j.fsi.2018.08.018DOI Listing
November 2018
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