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1.
Artigo em Inglês | MEDLINE | ID: mdl-33156504

RESUMO

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 (SO2/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 SO2 emission amount and S-SO2 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 SO2 and NO from CS blending with SS are higher than those from CS combustion alone, the conversion rate of SO2 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.

2.
ACS Appl Mater Interfaces ; 12(47): 53021-53028, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33170610

RESUMO

As a well-known electron-withdrawing group, benzo[c][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 Jsc values (over 20 mA/cm2) 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.

3.
Metabolism ; 115: 154432, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33197455

RESUMO

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.

4.
Mol Cell Biochem ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106913

RESUMO

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 (IC50) 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 IC50 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.

5.
Chin Med J (Engl) ; 133(20): 2437-2443, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32925290

RESUMO

BACKGROUND: Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle. METHODS: The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored. RESULTS: MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT. CONCLUSION: The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

6.
ACS Appl Mater Interfaces ; 12(36): 40590-40598, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32805919

RESUMO

In this work, a ternary blend strategy based on PBDB-T and two small molecular acceptors (IDTT-OB and IDT-PDOT-C6) 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 (Eloss) of charge carriers. We achieve a Eloss 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.

7.
Epilepsy Res ; 166: 106430, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32712511

RESUMO

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.

8.
Neuro Oncol ; 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32492707

RESUMO

BACKGROUND: Glioblastoma stem cells (GSCs) are a subpopulation of glioblastoma (GBM) cells that are critical for tumor invasion and treatment resistance. However, little is known about the function and mechanism of TRIM24 in GSCs. METHODS: Immunofluorescence, flow cytometry, and Western blot analyses were used to evaluate TRIM24 and CD133 expression profiles in GBM surgical specimens and GSC tumorspheres. Different TRIM24 expression levels in patients' tumors, as measured by both immunohistochemistry and Western blot, were related to their corresponding MRI data. Wound healing, Matrigel invasion and xenograft immunohistochemistry were conducted to determine GBM cell invasion. RESULTS: We identified that TRIM24 were coexpressed with CD133 and Nestin in GBM tissues and tumorsphere cells. Limiting dilution assays and xenotransplantation experiments illustrated that knockdown of TRIM24 expression reduced GSC self-renewal capacity and invasive growth. TRIM24 expression levels were positively associated with the volumes of peritumoral T2WI abnormality. Rescue experiments indicated TRIM24 participation in GBM infiltrative dissemination. Chromatin immunoprecipitation, reporter gene assay, PCR, Western blot and immunohistochemistry demonstrated that TRIM24 activated the expression of pluripotency transcription factor SOX2 to regulate GBM stemness and invasion in vitro and in vivo. Finally, the close relationship between TRIM24 and SOX2 was validated by testing samples enrolled in our study and exploring external databases. CONCLUSIONS: Our findings uncover essential roles of TRIM24-SOX2 axis in GBM stemness and invasiveness, suggesting TRIM24 as a potential target for effective GBM management.

9.
ACS Appl Mater Interfaces ; 12(27): 30627-30634, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32538621

RESUMO

Tremendous progress has been achieved on organic transistor-based photodetectors; however, because of the nonpositive correlation relationship between the photo/dark current ratio (P) and the gate voltage, the claimed best P, R (photoresponsivity), and D* (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 P of 3.83 × 103, R of 1.32 A W-1, and D* of 1.94 × 1012 Jones achieved simultaneously at Vg = -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.

10.
Acta Neurochir (Wien) ; 162(7): 1691-1699, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32440925

RESUMO

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.

11.
Front Oncol ; 10: 627, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457836

RESUMO

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.

12.
Jpn J Clin Oncol ; 50(3): 325-332, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32039443

RESUMO

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.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , DNA Tumoral Circulante/líquido cefalorraquidiano , Glioma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Feminino , Glioma/líquido cefalorraquidiano , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/líquido cefalorraquidiano , Recidiva Local de Neoplasia/genética , PTEN Fosfo-Hidrolase/genética , Proteínas de Ligação a Retinoblastoma/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética
13.
ACS Appl Mater Interfaces ; 12(4): 4638-4648, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31903738

RESUMO

Three noncovalently fused-ring electron acceptors (FOC6-IC, FOC6-FIC, and FOC2C6-2FIC) are synthesized. Single crystals of FOC6-IC and FOC2C6-2FIC 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 FOC2C6-2FIC, which help increase the crystallinity of acceptors and the charge mobility of the blends. Photovoltaic devices based on FOC2C6-2FIC give a power conversion efficiency of 12.36%, higher than 12.08% for FOC6-FIC and 10.80% for FOC6-IC.

14.
Fish Shellfish Immunol ; 98: 995-1000, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31734285

RESUMO

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.


Assuntos
Carpas/genética , Citocinas/genética , Proteínas de Peixes/genética , Expressão Gênica/imunologia , Rim Cefálico/imunologia , Leucócitos/imunologia , Animais , Carpas/imunologia , Citocinas/imunologia , Proteínas de Peixes/imunologia , Células Th17/imunologia
15.
Fish Shellfish Immunol ; 97: 500-508, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31883471

RESUMO

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.


Assuntos
Carpas/imunologia , Rim Cefálico/citologia , Interleucina-2/imunologia , Leucócitos/imunologia , Animais , Biologia Computacional , Citocinas/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Expressão Gênica , Rim Cefálico/imunologia , Interleucina-2/genética , RNA Mensageiro/imunologia , Transdução de Sinais
16.
Neuro Oncol ; 22(5): 625-638, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729527

RESUMO

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.

17.
Front Neurosci ; 13: 1137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708732

RESUMO

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: P < 0.001, PFS: P = 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: P = 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.

18.
Fish Shellfish Immunol ; 93: 508-516, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352118

RESUMO

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.


Assuntos
Carpas/genética , Carpas/imunologia , Interleucina-13/genética , Interleucina-4/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/imunologia , Animais , Evolução Molecular , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Macrófagos/metabolismo , Filogenia
19.
Nat Commun ; 10(1): 3038, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292441

RESUMO

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.

20.
Fish Shellfish Immunol ; 92: 315-321, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202965

RESUMO

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.


Assuntos
Carpas/genética , Carpas/imunologia , Proteínas de Peixes/genética , Interleucina-23/genética , Células Th17/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Rim Cefálico/imunologia , Interleucina-23/metabolismo , Leucócitos/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Transdução de Sinais/imunologia
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