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IFN-γ-mediated signaling in tumor cells can induce immunosuppressive responses and cause tumor resistance to immunotherapy. Blocking TGF-β promotes T lymphocyte infiltration and turns immunologically cold tumors into hot tumors, thereby improving the efficacy of immunotherapy. Several studies have shown that TGF-β inhibits IFN-γ signaling in immune cells. We thus sought to determine whether TGF-β affects IFN-γ signaling in tumor cells and plays a role in the development of acquired resistance to immunotherapy. TGF-β stimulation of tumor cells increased SHP1 phosphatase activity in an AKT-Smad3-dependent manner, decreased IFN-γ-mediated tyrosine phosphorylation of JAK1/2 and STAT1, and suppressed the expression of STAT1-dependent immune evasion-related molecules, e.g., PD-L1, IDO1, HVEM, and Gal-9. In a lung cancer mouse model, dual blockade of TGF-β and PD-L1 led to superior antitumor activity and prolonged survival compared to anti-PD-L1 therapy alone. However, prolonged combined treatment resulted in tumor resistance to immunotherapy and increased expression of PD-L1, IDO1, HVEM, and Gal-9. Interestingly, after initial anti-PD-L1 monotherapy, dual TGF-β and PD-L1 blockade promoted both immune evasion gene expression and tumor growth compared to that in tumors treated with continuous PD-L1 monotherapy. Alternatively, treatment with JAK1/2 inhibitor following initial anti-PD-L1 therapy effectively suppressed tumor growth and downregulated immune evasion gene expression in tumors, indicating the involvement of IFN-γ signaling in immunotherapy resistance development. These results demonstrate an unappreciated effect of TGF-β on the development of IFN-γ-mediated tumor resistance to immunotherapy.

To understand the influence of Kuroshio intrusion on the phytoplankton community, a field investigation was conducted in spring 2017 in the East China Sea (ECS), and 130 seawater samples were collected and analyzed. Trichodesmium comprised the highest cell abundance contributing about 66% of the total phytoplankton followed by diatoms (17%) and dinoflagellates (16%). The dominance of the Kuroshio Waters (KW) and the Taiwan Warm Currents (TWC) were higher than the Coastal Waters (CW). The vertical distribution of physicochemical parameters depicted the intrusion of KW at the bottom layer, but it failed to reach the surface as strong upwelling was not initiated. Therefore, the dissolved inorganic phosphate (DIP) concentrations and P/N ratios were the lowest in the CW and the upper water layers, which limited the diatom growth in this area. Besides, the dinoflagellates cell abundance was also lower except in the surface and CW, though they comprised the maximum richness of species among the phytoplankton community. However, the unique characteristics such as diazotrophy and gas vacuoles of Trichodesmium made the situation advantageous, and they comprised the maximum cell abundance in this area especially in KW and the TWC. Temperature, DIP and P/N ratios appeared to be the major environmental drivers for Trichodesmium proliferation in the ECS during the study period.

Genus Panax, as worldwide medicinal plants, has a medical history for thousands of years. Most of the entire genus are traditional ethnobotanical medicine in China, Myanmar, Thailand, Vietnam and L...

Objective: To explore the efficacy and safety of thoracoscopic resection for early-stage non-small cell lung cancer (NSCLC). Methods: A total of 110 patients with early-stage NSCLC admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2017 and December 2019 were enrolled and retrospectively analysed. Among them, 60 patients receiving thoracoscopic resection for lung cancer (LC) were assigned to the research group (Res group) and another 50 patients treated with routine open radical resection for LC were included in the control group (Con group). The following items of the two groups were evaluated and compared: treatment efficacy, operation indexes, VAS score, lung function, lung capacity, complications, 2-year tumour-free survival rate, 2-year survival rate, and quality of life (QoL). Results: The Res group showed significantly better efficacy, and lower incidence of complications and VAS score than the Con group. In addition, patients in the Res group experienced less intraoperative blood loss, earlier anal exhaust, shorter hospital stay and indwelling time of drainage tube as well as less drainage volume. Furthermore, better recovery in pulmonary function and lung capacity, and significantly higher 2-year tumour-free survival rate, 2-year survival rate as well as postoperative QoL were noted in the Res group compared with the Con group. Conclusion: Thoracoscopic resection for LC is effective in the treatment of patients with early-stage NSCLC. It can substantially shorten the hospital stay and indwelling time of drainage tube and reduce drainage volume and blood loss, with high safety.

Circular RNAs (circRNAs) have been demonstrated as potential biomarkers for the diagnosis and treatment of human diseases. Previous studies have unveiled the carcinogenic role of circRNA_102399 (circCNN2) in lung cancer. Through the UALCAN database, it was found that CNN2, the parent gene of circCNN2, was specifically highly expressed in human lung squamous cell carcinoma (LUSC) cells, but the regulatory mechanism of circCNN2 in LUSC is unclear. In this study, circCNN2 expression in LUSC cells was examined via RT-qPCR, and its effects on LUSC progression was verified through functional assays. The subcellular localization of circCNN2 was identified via FISH assay, and the underlying mechanism of circCNN2 on the activation of MAPK signaling pathway was determined through mechanism experiments. Results demonstrated that circCNN2 was upregulated in LUSC cells, and it promoted LUSC cell proliferation and invasion. Besides, circCNN2 acted as a competing endogenous RNA (ceRNA) to sponge miR-184 to upregulate E2F transcription factor 1 (E2F1) expression. Furthermore, it was verified that circCNN2 activated the generic mitogen-activated protein kinases (MAPK) signaling pathway through E2F1 and thus promoting LUSC progression. In a word, this study indicated that circCNN2 activated MAPK signaling pathway through the miR-184/E2F1 axis to promote proliferation and invasion of LUSC cells.

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.

Background. Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis-related lncRNAs in tumor development and providing a guidance for targeted therapy. Methods. Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first-order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance. Results. Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA-TF pairs among four glycolysis-related lncRNAs (FTX, LINC00472, PSMA3-AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis-related lncRNAs significantly associated with prognosis. Conclusions. This study identified three molecular subtypes that could guide personalized therapy. The four-lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.

Intubated general anesthesia and single-lung ventilation are considered mandatory for conventional thoracoscopic surgery. Non-intubated thoracoscopic thymectomy is technically challenging. The aim of this article was to present the initial results of non-intubated subxiphoid-subcostal thoracoscopic thymectomy (NI-STT) under LMA management for patients with thymic tumor or myasthenia gravis (MG) and to investigate the feasibility and safety of the procedure. A retrospective analysis of patients undergoing NI-STT for thymic tumor or MG at our department from January 2017 to January 2020 was performed. The clinical characteristics and perioperative outcomes of the patients were reviewed and analyzed. A total of 61 patients were received NI-STT in this analysis, of which 19 patients with MG undergone an extended thymectomy and the rest (n=42) undergone a partial thymectomy. The anesthetic induction duration, surgical duration and global operating room duration were 24.83±12.27 min, 118.75±32.49 min and 173.51±41.80 min, respectively. The lowest SpO2 and peak EtCO2 during operation were 96.15±2.93 mmHg and 41.79±7.53 mmHg, respectively. The mean duration of chest drainage and postoperative hospital stays were 1.87 days, and 2.91 days, respectively. Three cases had sore throat and irritable cough and two cases suffered nausea and vomiting occurred. one patient suffered from an atrial fibrillation, two patients experienced pneumonia, and one patient suffered wound infection, respectively. There were no phrenic nerve paralysis and mortality occurred in the study group. The postoperative pain was low on 1,3, 7, 14, 30, 90 and 180 postoperative days. NI-STT was a technically safe and feasible approach for treating thymic tumors or MG. It could be an alternative to intubated single-lung ventilation for thymectomy in selected patients.

With the development of information technology, educational data mining is increasingly widely used in colleges and universities. We explored the relationship between students’ personal situations, course performance, and final graduation destination and examined the relationship between various course performances. We analyzed the data of 1572 software college students from 2011 to 2014. Firstly, based on the students’ academic performance and personal information, we predicted the students’ future after graduation. Secondly, we used random forest to mine features or courses that influenced employment. Thirdly, we used the Apriori algorithm to investigate the implicit relationship between students’ scores in different courses. Experiments showed that students’ employment direction can be predicted based on student information, and there was a correlation between course scores, which could provide reasonable guidance for students’ learning and employment and assist university educators.

Macular fibrosis is a vital obstacle of vision acuity improvement of age‐related macular degeneration patients. This study was to investigate the effects of interleukin 2 (IL‐2) on epithelial‐mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and transforming growth factor β2 (TGF‐β2) expression in retinal pigment epithelial (RPE) cells. 10 μg/L IL‐2 was used to induce fibrosis in RPE cells for various times. Western blot was used to detect the EMT marker α‐smooth muscle actin (α‐SMA), ECM markers fibronectin (Fn) and type 1 collagen (COL‐1), TGF‐β2, and the activation of the JAK/STAT3 and NF‐κB signaling pathway. Furthermore, JAK/STAT3 and NF‐κB signaling pathways were specifically blocked by WP1066 or BAY11‐7082, respectively, and the expression of α‐SMA, COL‐1, Fn and TGF‐β2 protein were detected. Wound healing and Transwell assays were used to measure cell migration ability of IL‐2 with or without WP1066 or BAY11‐7082. After induction of IL‐2, the expressions of Fn, COL‐1, TGF‐β2 protein were significantly increased, and this effect was correlated with IL‐2 treatment duration, while α‐SMA protein expression did not change significantly. Both WP1066 and BAY11‐7082 could effectively downregulate the expression of Fn, COL‐1 and TGF‐β2 induced by IL‐2. What's more, both NF‐κB and JAK/STAT3 inhibitors could suppress the activation of the other signaling pathway. Additionally, JAK/STAT3 inhibitor WP1066 and NF‐κB inhibitor BAY 11‐7082 could obviously decrease RPE cells migration capability induced by IL‐2. IL‐2 promotes cell migration, ECM synthesis and TGF‐β2 expression in RPE cells via JAK/STAT3 and NF‐κB signaling pathways, which may play an important role in proliferative vitreoretinopathy., The study presented the non‐canonical effects of IL‐2 on the migration, mechanisms of extracellular matrix synthesis as well as the effects of TGF‐β2 expression in RPE cells via NF‐κB and JAK/STAT3 signaling pathway.

To investigate the effect of bottom-up factors (resource, hydrography, and environmental factors) on the phytoplankton and tintinnid microzooplankton communities, the research voyage was conducted in September 2017 at the East China Sea. An aggregate of 273 taxa of phytoplankton and 65 taxa of tintinnids were identified. Diatoms and dinoflagellates were the major groups of phytoplankton observed while the chain-forming diatoms were the most dominant group present in the study area. The coastal water and Kuroshio water influenced the concentration of dissolved inorganic nutrients as well as phytoplankton abundance. The concentration of dissolved inorganic nutrients increased vertically with the water depth while the phytoplankton and tintinnid abundance diminished. Redundancy analysis (RDA) and Pearson correlation analysis were conducted to analyze the relationship between the planktonic community and the ecological components. The RDA analysis between phytoplankton abundance and nutrients concentration showed that phytoplankton abundance increased with the increase in concentration of ammonium while a negative relationship was observed between phytoplankton abundance and nitrate, phosphate, and silicate. There was a significant positive correlation between the tintinnid microzooplankton and nanophytoplankton abundance as well as in their species richness which indicated that the tintinnid community depended upon nanophytoplankton for their feeding habit and growth rather than nutrients.

Marine picophytoplankton (Pico) as a major contributor to primary productivity in oligotrophic waters, play a very important role in marine material cycle and energy conversion, and their key role in the carbon cycle and global climate change is increasingly emphasized. To study the factors affecting the dynamic distribution of Synechococcus, Prochlorococcus, and picoeukaryotes in the East China Sea (ECS), a marginal sea of the Northwest Pacific, we investigated 27 stations in May 2017, and collected 148 samples of Pico and nutrients from the surface to the bottom. By means of flow cytometry, the abundance of Pico was measured, and then we estimated the carbon biomass and analyzed the distribution of Pico. Finally, combined with the ECS unique geographical situation and hydrological regime, we evaluated various factors affecting the Pico in the ECS. In Pico community, the picoeukaryotes cell abundance was between 0.49×102-1.44×104 cells/mL. Prochlorococcus ranged from 1.36×103-3.47×104 cells/mL and Synechococcus ranged from 0.69×103-1.15×105 cells/mL. Synechococcus was the most, both in abundance and in carbon biomass. Picoeukaryotes were the least in abundance, but has larger contribution to carbon biomass than Prochlorococcus. Water temperature, salinity, and stability of water column influenced Pico distribution. Picoeukaryotes were abundant in the shelf sea, whereas Synechococcus and Prochlorococcus were detected in the northeast of Taiwan, China. This study provided basic information for the study of Pico communities in the ECS and its adjacent marine ecosystem.

Background The widespread use of low-dose chest CT screening has improved the detection of early lung adenocarcinoma. Radical surgery is the best treatment strategy for patients with early lung adenocarcinoma; however, some patients present with postoperative recurrence and poor prognosis. Through this study, we hope to establish a model that can identify patients that are prone to recurrence and have poor prognosis after surgery for early lung adenocarcinoma. Materials and Methods We screened prognostic and relapse-related genes using The Cancer Genome Atlas (TCGA) database and the GSE50081 dataset from the Gene Expression Omnibus (GEO) database. The GSE30219 dataset was used to further screen target genes and construct a risk prognosis signature. Time-dependent ROC analysis, calibration degree analysis, and DCA were used to evaluate the reliability of the model. We validated the TCGA dataset, GSE50081, and GSE30219 internally. External validation was conducted in the GSE31210 dataset. Results A novel four-gene signature (INPP5B, FOSL2, CDCA3, RASAL2) was established to predict relapse-related survival outcomes in patients with early lung adenocarcinoma after surgery. The discovery of these genes may reveal the molecular mechanism of recurrence and poor prognosis of early lung adenocarcinoma. In addition, ROC analysis, calibration analysis and DCA were used to verify the genetic signature internally and externally. Our results showed that our gene signature had a good predictive ability for recurrence and prognosis. Conclusions We established a four-gene signature and predictive model to predict the recurrence and corresponding survival rates in patients with early lung adenocarcinoma after surgery. These may be helpful for reforumulating post-operative consolidation treatment strategies.

As an important part of data mining, educational data mining (EDM) has played a significant role in the field of education. This article reviews the development process of EDM, summarizes limited research directions of EDM from the past five years, and analyses the motivation and purpose of these studies, including the problems that have been solved. Next, the tools and algorithms used are introduced according to the referenced literature. Finally, this article discusses and summarizes further research directions based on previous research results and some thoughts with the hopes of offering researchers future research directions.

Different geographical environment has a certain influence on the accumulation of fungi elements and chemical components. However, our knowledge is limited to elucidate the fungi elements in response to heterogeneous environmental and the quality differences among different habitats. Here, multielement analysis, FTIR spectrum, and feature-level fusion technique combined with chemometrics were used to study Wolfiporia cocos from different geographical areas, different sampling sites and different altitude sources. From the results, (1) there is significant difference in element content of samples from different sampling sites and no positive correlation with geographical ranges. (2) There is a correlation between elevation and elements, and relatively low elevation (

Aims The epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and cell migration of residual lens cells constitute the canonical mechanisms of posterior capsular opacification (PCO). Recently, myofibroblast cell apoptosis is also observed in the rabbit PCO model. However, whether cell apoptosis is a key factor affecting PCO and regulates EMT/ECM synthesis/cell migration remains obscure. Main methods Flow cytometry was utilized to assess cell cycle and apoptosis. EMT marker α-smooth muscle actin (α-SMA), ECM markers fibronectin (Fn), type 1 collagen (COL-1) and apoptosis-associated proteins in the presence or absence of EMT/ECM inhibitor (LY2109761), apoptosis inhibitor (ZVAD) or apoptosis activator (BTSA1) were detected by Western blotting. Downstream effector genes in apoptosis-induced lens epithelial cell lines (LECs) were analyzed by RNA-seq. Gene silencing and overexpression in LECs were performed to validate the role of effector genes. We measured cell migration capability using Wound healing and Transwell assays. Key findings We found that TGF-β2 induced cell apoptosis. ZVAD inhibited α-SMA expression in the ex vivo capsule model and decreased the expression of both EMT and ECM markers in TGF-β2-treated LECs. RNA-seq revealed that FILIP1L was significantly decreased in apoptosis-activated cells. We further validated that the knockdown of FILIP1L could enhance EMT and ECM synthesis and promote cell migration and that FILIP1L overexpression could reverse these effects. Apoptosis might contribute to TGF-β2-induced EMT and ECM synthesis during PCO, and these contributions are mediated by FILIP1L. Significance Our findings uncover the role of apoptosis in PCO development and provide new drug targets.

Paris polyphylla var. yunnanensis, as perennial plants, its quality is closely related to growth period. Different harvest years determine the dry matter accumulation of its medicinal parts and the dynamic accumulation of active ingredients, as well as its economic value and medicinal value. Therefore, it is necessary to establish a systematic evaluation method for the identification and evaluation of P. polyphylla var. yunnanensis with different growth years. Deep learning has a powerful ability in recognition. This study extends it to the identification analysis of medicinal plants from the perspective of spectrum. For the first time, two-dimensional correlation spectroscopy (2DCOS) based on the attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) combined with residual neural network (Resnet) was used to identify growth years. 525 samples were collected, 4725 2DCOS images were drawn, and the dry matter accumulation in rhizomes of different growth years and different sampling sites were briefly analyzed. The results show that the eight-year-old P. polyphylla var. yunnanensis in Dali has higher economic value and medicinal value. The synchronous 2DCOS models based on ATR-FTIR can realize the identification of growth years with accuracy of 100%. Synchronous 2DCOS are more suitable for the identification of medicinal plants with complex systems. 2DCOS images with different colors and second derivative processing cannot optimize the modeling results. In summary, the method we established is innovative and feasible. It not only solved the identification of growth years, expanded the application field of deep learning, but could also be extended to further research on other medicinal plants.

Spectral analysis has the characteristics of fast and nondestructive. In order to conform to the development of the times, a practical method beyond the traditional spectral analysis was established. For the first time, the two-dimensional correlation spectroscopy (2DCOS) images of Fourier-transform mid-infrared spectroscopy combined with the Residual Neural Network (ResNet) was used for the identification and analysis of 12 Paris species, and the second derivative 2DCOS rarely involved in previous researchers was established. Besides, the fusion strategy of 2DCOS images based on feature bands was first proposed for modeling analysis. From the results, (1) 2DCOS combined with ResNet can successfully identify 12 Paris species. (2) 2DCOS is a powerful tool for identification, whether it is used for image visual analysis or modeling analysis. (3) Compared with asynchronous 2DCOS, synchronous 2DCOS is more suitable for the identification and analysis of complex mixed systems such as traditional Chinese medicine. (4) The modeling based on feature bands fusion strategy of 2DCOS has better model performance and is also suitable for the analysis of small samples. To sum up, what we proposed is an innovative and feasible method with wide applicability, which can not only solve the problem of identifying Paris, provide ideas and methods for the selection of spectral types and feature bands, but also provide practical reference for the research in analytical chemistry and other related fields.

The catalytic activity trends of four different metal surfaces (Rh, Pd, Pt and Ni) for N 2 O direct catalytic decomposition were analyzed and predicted using density functional theory (DFT). Some adsorption features on different metal surfaces were investigated, such as the structure, electron and energy of two important N 2 O adsorption sites: the top site and the flat-bidentate site. The DFT results show that the adsorption energy of N 2 O on the top site over Rh, Pd and Pt metal surfaces was negative, which indicates that N 2 O can be easily adsorbed on these metal surfaces. The difficulty of the N–O bond breakage in the flat-adsorbed N 2 O was analyzed by combining the molecular structure, density of state and charge density to predict the catalytic activity of different metal surfaces. The catalytic activity trend of different metal surfaces for N 2 O decomposition is determined as Rh > Pd > Pt > Ni, which is consistent with the corresponding experimental results.

Pt-Ni bimetallic catalysts and the corresponding monometallic Pt catalysts supported on active carbon were prepared by incipient wetness impregnation and characterized by X-ray diffraction, N2 adsorption, and NH3-temperature programmed desorption. Their activities for decalin dehydrogenation were investigated at a superheated liquid film state in a batch reactor. The effects of temperature, impregnation sequence, and Pt/Ni molar ratio on the dehydrogenation activity and the naphthalene yield were investigated. The results show that the Pt-Ni bimetallic catalyst significantly enhanced hydrogen evolution compared with either Ni or Pt monometallic catalyst. The highest dehydrogenation conversion and naphthalene yield were obtained when the Pt/Ni molar ratio was 1:1 and Pt was impregnated first. The experimental results were correlated with density functional theory calculations of hydrogen binding energy (HBE) on different catalytic surfaces. The correlation confirmed that bimetallic surfaces with stronger HBEs had higher dehydrogenation activities.

Pt was replaced with tungsten carbide (WC) in the Ni–Pt structure for decalin dehydrogenation on base of their similar properties. The catalytic performance of Ni–WC catalyst was predicted by density functional theory (DFT) calculations and further confirmed by dehydrogenation reaction. Replacing Pt with WC significantly reduces the side reactions such as ring-opening and coking. The highest conversion of decalin is about 93 % and the selectivity to naphthalene is nearly 100 % over Ni–WC/AC catalyst. The improved catalytic activity of Ni–WC/AC demonstrates the feasibility to replace Pt with WC as an active and less expensive dehydrogenation catalyst. .

Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery.

WC-doped Ni over an active carbon catalyst (Ni–WC/AC), prepared by incipient wetness impregnation, is proposed as an anode for the amplified electrochemical oxidation of glucose in 0.1 M KOH solution. Cyclic voltammetry and morphology characterizations were used to explore these electrocatalysts. It was found that Ni–WC/AC catalysts were nanoparticles with a diameter of 10 nm and the 20%wtNi–20%wtWC/AC catalyst showed superior electrocatalytic activity toward glucose oxidation. The extraordinary activity obtained at the 20%wtNi–20%wtWC/AC modified glass carbon electrode (GCE) is attributed to the synergistic effect between Ni and WC toward glucose electroxidation.