43 results on '"Wentao Deng"'
Search Results
2. Identification of clinical prognostic factors and analysis of ferroptosis-related gene signatures in the bladder cancer immune microenvironment
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Jiafu Ma, Jianting Hu, Leizuo Zhao, Zixuan Wu, Rongfen Li, and Wentao Deng
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BLCA ,FRGs ,Immunity ,m6a and immune checkpoint ,Drug prediction ,CNV ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Bladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and poses a significant burden in terms of both incidence and mortality rates on a global scale. Among all BLCA cases, non-muscle invasive bladder cancer constitutes approximately 75% of the total. In recent years, the concept of ferroptosis, an iron-dependent form of regulated cell death marked by the accumulation of lipid peroxides, has captured the attention of researchers worldwide. Nevertheless, the precise involvement of ferroptosis-related genes (FRGs) in the anti-BLCA response remains inadequately elucidated. Methods The integration of BLCA samples from the TCGA and GEO datasets facilitated the quantitative evaluation of FRGs, offering potential insights into their predictive capabilities. Leveraging the wealth of information encompassing mRNAsi, gene mutations, CNV, TMB, and clinical features within these datasets further enriched the analysis, augmenting its robustness and reliability. Through the utilization of Lasso regression, a prediction model was developed, enabling accurate prognostic assessments within the context of BLCA. Additionally, co-expression analysis shed light on the complex relationship between gene expression patterns and FRGs, unraveling their functional relevance and potential implications in BLCA. Results FRGs exhibited increased expression levels in the high-risk cohort of BLCA patients, even in the absence of other clinical indicators, suggesting their potential as prognostic markers. GSEA revealed enrichment of immunological and tumor-related pathways specifically in the high-risk group. Furthermore, notable differences were observed in immune function and m6a gene expression between the low- and high-risk groups. Several genes, including MYBPH, SOST, SPRR2A, and CRNN, were found to potentially participate in the oncogenic processes underlying BLCA. Additionally, CYP4F8, PDZD3, CRTAC1, and LRTM1 were identified as potential tumor suppressor genes. Significant discrepancies in immunological function and m6a gene expression were observed between the two risk groups, further highlighting the distinct molecular characteristics associated with different prognostic outcomes. Notably, strong correlations were observed among the prognostic model, CNVs, SNPs, and drug sensitivity profiles. Conclusions FRGs are associated with the onset and progression of BLCA. A FRGs signature offers a viable alternative to predict BLCA, and these FRGs show a prospective research area for BLCA targeted treatment in the future.
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- 2024
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3. Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management
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Wentao Deng, Yu Yan, Peipei Zhuang, Xiaoxu Liu, Ke Tian, Wenfang Huang, and Cai Li
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hydrogels ,nanocapsules ,bupivacaine ,anesthetics ,pain management ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.HIGHLIGHTS Preparation and characterization of CS-GP/PC polymeric hydrogel system. BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution. Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells. Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.
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- 2022
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4. KxCy phase induced expanded interlayer in ultra‐thin carbon toward full potassium‐ion capacitors
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Xinglan Deng, Ye Tian, Kangyu Zou, Jun Chen, Xuhuan Xiao, Shusheng Tao, Zirui Song, Wentao Deng, Hongshuai Hou, Guoqiang Zou, and Xiaobo Ji
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expanded interlayer ,KxCy phase ,potassium‐ion capacitors ,themal‐induced ,ultra‐thin carbon ,Production of electric energy or power. Powerplants. Central stations ,TK1001-1841 - Abstract
Abstract Carbonaceous materials have been regarded as highly promising anode candidates for potassium storage with their cost‐effectiveness and environmental benignity. However, low specific capacity and difficulty in large‐scale synthesis largely hinder their further development. Herein, a thermal‐induced potassium–carbon alloy phase (KxCy) with the expanded interlayer spacing strategy is first put forward. Through in situ high‐temperature X‐ray diffraction, a K2C2 phase is evoked by thermal energy during the in‐situ carbonization process of carbon quantum dots intermediate derived from potassium‐containing precursors, whereas no lithium or sodium–carbon alloy phase is observed from lithium/sodium‐containing precursors. The as‐obtained ultra‐thin carbon nanosheets achieve adjustable layer spacing, preparation in bulk, delivering reversible potassium storage of 403.4 mAh g−1 at 100 mA g−1 and 161.2 mAh g−1 even at 5.0 A g−1, which is one of the most impressive K‐storage performances reported so far with great potential application. Furthermore, the assembled potassium‐ion hybrid capacitor by combining the impressive CFMs‐900 anode with the three‐dimensional framework‐activated carbon delivers a high energy‐power density of 251.7 Wh kg−1 at 250 W kg−1 with long‐term stability. This study opens a scalable avenue to realize the expanded interlayer spacing, which can be extended to other multicarboxyl potassium salts and can provide approach for the design of high‐performance carbon anode materials for potassium storage.
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- 2022
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5. Metal–Organic Framework Materials for Electrochemical Supercapacitors
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Ziwei Cao, Roya Momen, Shusheng Tao, Dengyi Xiong, Zirui Song, Xuhuan Xiao, Wentao Deng, Hongshuai Hou, Sedat Yasar, Sedar Altin, Faith Bulut, Guoqiang Zou, and Xiaobo Ji
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Metal–organic frameworks (MOFs) ,Electrochemistry ,Supercapacitors ,Electrode materials ,Technology - Abstract
Abstract Exploring new materials with high stability and capacity is full of challenges in sustainable energy conversion and storage systems. Metal–organic frameworks (MOFs), as a new type of porous material, show the advantages of large specific surface area, high porosity, low density, and adjustable pore size, exhibiting a broad application prospect in the field of electrocatalytic reactions, batteries, particularly in the field of supercapacitors. This comprehensive review outlines the recent progress in synthetic methods and electrochemical performances of MOF materials, as well as their applications in supercapacitors. Additionally, the superiorities of MOFs-related materials are highlighted, while major challenges or opportunities for future research on them for electrochemical supercapacitors have been discussed and displayed, along with extensive experimental experiences.
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- 2022
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6. Natural Stibnite for Lithium-/Sodium-Ion Batteries: Carbon Dots Evoked High Initial Coulombic Efficiency
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Yinger Xiang, Laiqiang Xu, Li Yang, Yu Ye, Zhaofei Ge, Jiae Wu, Wentao Deng, Guoqiang Zou, Hongshuai Hou, and Xiaobo Ji
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Carbon dots ,Sb2S3 ,Initial Coulombic efficiency ,Interfacial bond ,Anode ,Technology - Abstract
Highlights The chemical process of local oxidation–partial reduction–deep coupling for stibnite reduction of carbon dots (CDs) is revealed by in-situ high-temperature X-ray diffraction. Sb2S3@xCDs anode delivers high initial coulombic efficiency in lithium ion batteries (85.2%) and sodium ion batteries (82.9%), respectively. C–S bond influenced by oxygen-rich carbon matrix can restrain the conversion of sulfur to sulfite, well confirmed by X-ray photoelectron spectroscopy characterization of solid electrolyte interphase layers helped with density functional theory calculations. CDs-induced Sb–O–C bond is proved to effectively regulate the interfacial electronic structure. Abstract The application of Sb2S3 with marvelous theoretical capacity for alkali metal-ion batteries is seriously limited by its poor electrical conductivity and low initial coulombic efficiency (ICE). In this work, natural stibnite modified by carbon dots (Sb2S3@xCDs) is elaborately designed with high ICE. Greatly, chemical processes of local oxidation–partial reduction–deep coupling for stibnite reduction of CDs are clearly demonstrated, confirmed with in situ high-temperature X-ray diffraction. More impressively, the ICE for lithium-ion batteries (LIBs) is enhanced to 85%, through the effect of oxygen-rich carbon matrix on C–S bonds which inhibit the conversion of sulfur to sulfite, well supported by X-ray photoelectron spectroscopy characterization of solid electrolyte interphase layers helped with density functional theory calculations. Not than less, it is found that Sb–O–C bonds existed in the interface effectively promote the electronic conductivity and expedite ion transmission by reducing the bandgap and restraining the slip of the dislocation. As a result, the optimal sample delivers a tremendous reversible capacity of 660 mAh g−1 in LIBs at a high current rate of 5 A g−1. This work provides a new methodology for enhancing the electrochemical energy storage performance of metal sulfides, especially for improving the ICE.
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- 2022
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7. Carbon dots for ultrastable solid‐state batteries
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Laiqiang Xu, Hanyu Tu, Fangjun Zhu, Yinger Xiang, Zheng Luo, Susu Fang, Wentao Deng, Guoqiang Zou, Hongshuai Hou, and Xiaobo Ji
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carbon dots ,Li+ conductor ,LiF ,selective ion transport ,solid‐state batteries ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Abstract Among the solid electrolytes for solid‐state Li batteries, polymer electrolytes are actively explored on the basis of the good interfacial contact and easy making, while it is still constrained by slow ionic transport and low lithium ion transference number. Herein, functional carbon dots‐based Li+ conductor (CD‐Li) is designed to improve the dynamics and selectivity of Li+ transport in polyethylene oxide (PEO) electrolyte. High ionic conductivity (1.0 × 10−4 S/cm, 25 °C) and Li+ transference number (0.60) were successfully achieved within the CD‐Li‐based PEO composite electrolyte, which could be attributed to the enhanced chain movement and the limited motion of anion. Moreover, the characteristics of big volume of individual anions of CD‐Li can provide more free Li+. As well, benefiting from the existence of F atom in the CD‐Li, in‐situ constructed LiF‐containing interfacial layer is in favor of maintaining the interface stability and facilitating the rapid transmission of Li ions. The composite electrolyte with CD‐Li can address the ionic conductivity issues accompanied with strengthening the interfacial stability. The distinctive composite electrolyte realizes the stable cycle performance for Li/LiFePO4 and Li/LiNi0.5Co0.2Mn0.3O2 batteries. The exploration of multifunctional carbon dot fillers provides new ideas for the efficient development of composite electrolytes.
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- 2022
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8. Effects of Gas Composition on the Lipid Oxidation and Fatty Acid Concentration of Tilapia Fillets Treated with In-Package Atmospheric Cold Plasma
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Xiaohan Sang, Yuanyuan Wang, Jiamei Wang, Zhicheng Cai, Lixian Zeng, Wentao Deng, Jianhao Zhang, and Zhumao Jiang
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cold plasma ,lipid oxidation ,tilapia fillets ,gas composition ,fatty acid ,Chemical technology ,TP1-1185 - Abstract
Cold plasma (CP) is a non-thermal preservation technology that has been successfully used to decontaminate and extend the shelf life of aquatic products. However, the preservation effect of CP treatment is determined by several factors, including voltage, time, and gas compositions. Therefore, this study aimed to investigate the effects of gas composition (GasA: 10% O2, 50% N2, 40% CO2; GasB: air; GasC: 30% O2, 30% N2, 40% CO2) on the lipid oxidation of tilapia fillets treated after CP treatment. Changes in the lipid oxidation values, the percentages of fatty acids, and sensory scores were studied during 8 d of refrigerator storage. The results showed that the CP treatment significantly increased all the primary and secondary lipid oxidation values measured in this study, as well as the percentages of saturated fatty acids, but decreased the percentages of unsaturated fatty acids, especially polyunsaturated fatty acids. The lipid oxidation values were significantly increased in the GasC-CP group. After 8 d, clearly increased percentages of saturated fatty acids, a low level of major polyunsaturated fatty acids (especially linoleic (C18:2n-6)), and a decrease in the percentages of eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) were found in GasC-CP; that is, the serious oxidation of lipids was found in the high O2 concentration group. In addition, the sensory score was also lower than that of the hypoxia CP group. Therefore, high O2 concentrations can enhance lipid oxidation and the changes in the fatty acid concentration. Controlling the O2 concentration is reasonable to limit the degree to which lipids are oxidized in tilapia after the in-package CP treatment.
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- 2024
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9. Transcriptome Analysis Reveals Novel Insights into the Hyperaccumulator Phytolacca acinosa Roxb. Responses to Cadmium Stress
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Qin Xie, Wentao Deng, Yi Su, Liying Ma, Haijun Yang, Feihong Yao, and Wanhuang Lin
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Phytolacca acinosa Roxb. ,cadmium stress ,phytoremediation ,transcriptome ,regulatory mechanism ,Botany ,QK1-989 - Abstract
Cadmium (Cd) is a highly toxic heavy metal that causes serious damage to plant and human health. Phytolacca acinosa Roxb. has a large amount of aboveground biomass and a rapid growth rate, and it has been identified as a novel type of Cd hyperaccumulator that can be harnessed for phytoremediation. However, the molecular mechanisms underlying the response of P. acinosa to Cd2+ stress remain largely unclear. In this study, the phenotype, biochemical, and physiological traits of P. acinosa seeds and seedlings were analyzed under different concentrations of Cd2+ treatments. The results showed higher Cd2+ tolerance of P. acinosa compared to common plants. Meanwhile, the Cd2+ content in shoots reached 449 mg/kg under 10 mg/L Cd2+ treatment, which was obviously higher than the threshold for Cd hyperaccumulators. To investigate the molecular mechanism underlying the adaptability of P. acinosa to Cd stress, RNA-Seq was used to examine transcriptional responses of P. acinosa to Cd stress. Transcriptome analysis found that 61 genes encoding TFs, 48 cell wall-related genes, 35 secondary metabolism-related genes, 133 membrane proteins and ion transporters, and 96 defense system-related genes were differentially expressed under Cd2+ stress, indicating that a series of genes were involved in Cd2+ stress, forming a complex signaling regulatory mechanism. These results provide new scientific evidence for elucidating the regulatory mechanisms of P. acinosa response to Cd2+ stress and new clues for the molecular breeding of heavy metal phytoremediation.
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- 2024
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10. Data-driven learning how oncogenic gene expression locally alters heterocellular networks
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David J. Klinke II, Audry Fernandez, Wentao Deng, Atefeh Razazan, Habibolla Latifizadeh, and Anika C. Pirkey
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Science - Abstract
While mechanistic models play increasing roles in immuno-oncology, hand network curation is current practice. Here the authors use a Bayesian data-driven approach to infer how expression of a secreted oncogene alters the cellular landscape within the tumor.
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- 2022
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11. Ultra-Low-Dose Pre-Metallation Strategy Served for Commercial Metal-Ion Capacitors
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Zirui Song, Guiyu Zhang, Xinglan Deng, Kangyu Zou, Xuhuan Xiao, Roya Momen, Abouzar Massoudi, Wentao Deng, Jiugang Hu, Hongshuai Hou, Guoqiang Zou, and Xiaobo Ji
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Coupled interface ,Pre-metallation ,Metal oxalate ,Decomposition potential ,Technology - Abstract
Highlights Interfacial bonding strategy has been successfully applied to address the high overpotential issue of sacrificial additives, which reduced the decompositon potential of Na2C2O4 from 4.50 to 3.95 V. Ultra-low-dose technique assisted commercial sodium ion capacitor (AC//HC) could deliver a remarkable energy density of 118.2 Wh kg−1 as well as excellent cycle stability. In-depth decomposition mechanism of sacrificial compound and the relative influence after pre-metallation were revealed by advanced in situ and ex situ characterization approaches. Abstract Sacrificial pre-metallation strategy could compensate for the irreversible consumption of metal ions and reduce the potential of anode, thereby elevating the cycle performance as well as open-circuit voltage for full metal ion capacitors (MICs). However, suffered from massive-dosage abuse, exorbitant decomposition potential, and side effects of decomposition residue, the wide application of sacrificial approach was restricted. Herein, assisted with density functional theory calculations, strongly coupled interface (M–O–C, M = Li/Na/K) and electron donating group have been put forward to regulate the band gap and highest occupied molecular orbital level of metal oxalate (M2C2O4), reducing polarization phenomenon and Gibbs free energy required for decomposition, which eventually decrease the practical decomposition potential from 4.50 to 3.95 V. Remarkably, full sodium ion capacitors constituted of commercial materials (activated carbon//hard carbon) could deliver a prominent energy density of 118.2 Wh kg−1 as well as excellent cycle stability under an ultra-low dosage pre-sodiation reagent of 15–30 wt% (far less than currently 100 wt%). Noteworthily, decomposition mechanism of sacrificial compound and the relative influence on the system of MICs after pre-metallation were initially revealed by in situ differential electrochemical mass spectrometry, offering in-depth insights for comprehending the function of cathode additives. In addition, this breakthrough has been successfully utilized in high performance lithium/potassium ion capacitors with Li2C2O4/K2C2O4 as pre-metallation reagent, which will convincingly promote the commercialization of MICs.
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- 2022
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12. Crack-free single-crystalline Co-free Ni-rich LiNi0.95Mn0.05O2 layered cathode
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Lianshan Ni, Ruiting Guo, Susu Fang, Jun Chen, Jinqiang Gao, Yu Mei, Shu Zhang, Wentao Deng, Guoqiang Zou, Hongshuai Hou, and Xiaobo Ji
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Single-crystalline ,Co-free Ni-rich cathodes ,Intergranular microcracking ,H2↔H3 phase transition ,Cycling stability ,Mechanical engineering and machinery ,TJ1-1570 ,Electronics ,TK7800-8360 - Abstract
The rapid growth in global electric vehicles (EVs) sales has promoted the development of Co-free, Ni-rich layered cathodes for state-of-the-art high energy-density, inexpensive lithium-ion batteries (LIBs). However, progress in their commercial use has been seriously hampered by exasperating performance deterioration and safety concerns. Herein, a robust single-crystalline, Co-free, Ni-rich LiNi0.95Mn0.05O2 (SC-NM95) cathode is successfully designed using a molten salt-assisted method, and it exhibits better structural stability and cycling durability than those of polycrystalline LiNi0.95Mn0.05O2 (PC-NM95). Notably, the SC-NM95 cathode achieves a high discharge capacity of 218.2 mAh g−1, together with a high energy density of 837.3 Wh kg−1 at 0.1 C, mainly due to abundant Ni2+/Ni3+ redox. It also presents an outstanding capacity retention (84.4%) after 200 cycles at 1 C, because its integrated single-crystalline structure effectively inhibits particle microcracking and surface phase transformation. In contrast, the PC-NM95 cathode suffers from rapid capacity fading owing to the nucleation and propagation of intergranular microcracking during cycling, facilitating aggravated parasitic reactions and rock-salt phase accumulation. This work provides a fundamental strategy for designing high-performance single-crystalline, Co-free, Ni-rich cathode materials and also represents an important breakthrough in developing high-safe, low-cost, and high-energy LIBs.
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- 2022
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13. On-chip terahertz isolator with ultrahigh isolation ratios
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Shixing Yuan, Liao Chen, Ziwei Wang, Wentao Deng, Zhibo Hou, Chi Zhang, Yu Yu, Xiaojun Wu, and Xinliang Zhang
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Science - Abstract
Nonreciprocal devices are crucial in scientific research and practical applications at all frequencies. Here the authors demonstrate an integrated terahertz optical isolator based on the magneto-optical effect in a nonreciprocal resonator.
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- 2021
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14. Ultrahigh-speed graphene-based optical coherent receiver
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Yilun Wang, Xiang Li, Zhibin Jiang, Lei Tong, Wentao Deng, Xiaoyan Gao, Xinyu Huang, Hailong Zhou, Yu Yu, Lei Ye, Xi Xiao, and Xinliang Zhang
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Science - Abstract
Graphene-based photodetectors have many advantages for applications. Here, the authors demonstrate a high-speed optical coherent receiver for optical communications based on graphene-on-plasmonic slot waveguide photodetectors.
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- 2021
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15. Interleukin-12 elicits a non-canonical response in B16 melanoma cells to enhance survival
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Christina N. Byrne-Hoffman, Wentao Deng, Owen McGrath, Peng Wang, Yon Rojanasakul, and David J. Klinke
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Interleukins ,Intracellular signaling ,Cytokine ,JAK-STAT signaling ,PI3K-AKT signaling ,Non-canonical ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract Background Oncogenesis rewires signaling networks to confer a fitness advantage to malignant cells. For instance, the B16F0 melanoma cell model creates a cytokine sink for Interleukin-12 (IL-12) to deprive neighboring cells of this important anti-tumor immune signal. While a cytokine sink provides an indirect fitness advantage, does IL-12 provide an intrinsic advantage to B16F0 cells? Methods Acute in vitro viability assays were used to compare the cytotoxic effect of imatinib on a melanoma cell line of spontaneous origin (B16F0) with a normal melanocyte cell line (Melan-A) in the presence of IL-12. The results were analyzed using a mathematical model coupled with a Markov Chain Monte Carlo approach to obtain a posterior distribution in the parameters that quantified the biological effect of imatinib and IL-12. Intracellular signaling responses to IL-12 were compared using flow cytometry in 2D6 cells, a cell model for canonical signaling, and B16F0 cells, where potential non-canonical signaling occurs. Bayes Factors were used to select among competing signaling mechanisms that were formulated as mathematical models. Analysis of single cell RNAseq data from human melanoma patients was used to explore generalizability. Results Functionally, IL-12 enhanced the survival of B16F0 cells but not normal Melan-A melanocytes that were challenged with a cytotoxic agent. Interestingly, the ratio of IL-12 receptor components (IL12RB2:IL12RB1) was increased in B16F0 cells. A similar pattern was observed in human melanoma. To identify a mechanism, we assayed the phosphorylation of proteins involved in canonical IL-12 signaling, STAT4, and cell survival, Akt. In contrast to T cells that exhibited a canonical response to IL-12 by phosphorylating STAT4, IL-12 stimulation of B16F0 cells predominantly phosphorylated Akt. Mechanistically, the differential response in B16F0 cells is explained by both ligand-dependent and ligand-independent aspects to initiate PI3K-AKT signaling upon IL12RB2 homodimerization. Namely, IL-12 promotes IL12RB2 homodimerization with low affinity and IL12RB2 overexpression promotes homodimerization via molecular crowding on the plasma membrane. Conclusions The data suggest that B16F0 cells shifted the intracellular response to IL-12 from engaging immune surveillance to favoring cell survival. Identifying how signaling networks are rewired in model systems of spontaneous origin can inspire therapeutic strategies in humans. Plain english summary Interleukin-12 is a key cytokine that promotes anti-tumor immunity, as it is secreted by antigen presenting cells to activate Natural Killer cells and T cells present within the tumor microenvironment. Thinking of cancer as an evolutionary process implies that an immunosuppressive tumor microenvironment could arise during oncogenesis by interfering with endogenous anti-tumor immune signals, like IL-12. Previously, we found that B16F0 cells, a cell line derived from a spontaneous melanoma, interrupts this secreted heterocellular signal by sequestering IL-12, which provides an indirect fitness advantage. Normally, IL-12 signals via a receptor comprised of two components, IL12RB1 and IL12RB2, that are expressed in a 1:1 ratio and activates STAT4 as a downstream effector. Here, we report that B16F0 cells gain an intrinsic advantage by rewiring the canonical response to IL-12 to instead initiate PI3K-AKT signaling, which promotes cell survival. The data suggest a model where overexpressing one component of the IL-12 receptor, IL12RB2, enables melanoma cells to shift the functional response via both IL-12-mediated and molecular crowding-based IL12RB2 homodimerization. To explore the generalizability of these results, we also found that the expression of IL12RB2:IL12RB1 is similarly skewed in human melanoma based on transcriptional profiles of melanoma cells and tumor-infiltrating lymphocytes. Additional file 6: Video abstract. (MP4 600 kb)
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- 2020
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16. Crystalline Hydrate Dehydration Sensing Based on Integrated Terahertz Whispering Gallery Mode Resonators
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Zhibo Hou, Shixing Yuan, Wentao Deng, Jiahua Cai, Yaqin Qiu, Yunong Zhao, Ziwei Wang, Liao Chen, Huan Liu, Xiaojun Wu, and Xinliang Zhang
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terahertz (THz) ,whispering gallery mode (WGM) ,crystalline hydrate ,dehydration ,sensing ,Chemical technology ,TP1-1185 - Abstract
Water molecules play a very important role in the hydration and dehydration process of hydrates, which may lead to distinct physical and chemical properties, affecting their availability in practical applications. However, miniaturized, integrated sensors capable of the rapid, sensitive sensing of water molecules in the hydrate are still lacking, limiting their proliferation. Here, we realize the high-sensitivity sensing of water molecules in copper sulfate pentahydrate (CuSO4·5H2O), based on an on-chip terahertz whispering gallery mode resonator (THz-WGMR) fabricated on silicon material via CMOS-compatible technologies. An integrated THz-WGMR with a high-Q factor of 3305 and a resonance frequency of 410.497 GHz was proposed and fabricated. Then, the sensor was employed to distinguish the CuSO4·xH2O (x = 5, 3, 1). The static characterization from the CuSO4·5H2O to the copper sulfate trihydrate (CuSO4·3H2O) experienced blueshifts of 0.55 GHz/μmol, whereas the dehydration process of CuSO4·3H2O to copper sulfate monohydrate (CuSO4·H2O) exhibited blueshifts of 0.21 GHz/μmol. Finally, the dynamic dehydration processes of CuSO4·5H2O to CuSO4·3H2O at different temperatures were monitored. We believe that our proposed THz-WGMR sensors with highly sensitive substance identification capabilities can provide a versatile and integrated platform for studying the transformation between substances, contributing to hydrated/crystal water-assisted biochemical applications.
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- 2022
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17. Antenna-integrated silicon–plasmonic graphene sub-terahertz emitter
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Zhibin Jiang, Yilun Wang, Liao Chen, Yu Yu, Shixing Yuan, Wentao Deng, Ruolan Wang, Ziwei Wang, Qizhi Yan, Xiaojun Wu, and Xinliang Zhang
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Applied optics. Photonics ,TA1501-1820 - Abstract
Photo-mixing with its advantages of ultra-large bandwidth and precise tunability has emerged as an important technique for terahertz (THz) wave generation. Recently, graphene photodetectors exhibiting a large bandwidth are expected to further boost the development of integrated THz emitters. Here, we fabricate a sub-THz emitter based on a large-bandwidth silicon–plasmonic graphene (SPG) photodetector integrated with a broadband rounded bow-tie THz antenna. The SPG sub-THz emitter is experimentally demonstrated to emit sub-THz waves with a radiation spectrum from 50 to 300 GHz. A maximum sub-THz emission power of 5.4 nW is obtained at 145 GHz with only 3 mW input light power. The SPG sub-THz emitter can be fabricated by a CMOS-compatible process, which offers enormous opportunities for its use in a variety of THz applications.
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- 2021
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18. Multiple High-Affinity K+ Transporters and ABC Transporters Involved in K+ Uptake/Transport in the Potassium-Hyperaccumulator Plant Phytolacca acinosa Roxb
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Qin Xie, Liying Ma, Peng Tan, Wentao Deng, Chao Huang, Deming Liu, Wanhuang Lin, and Yi Su
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Phytolacca acinosa ,potassium transport ,high-affinity K+ transporters ,ABC transporters ,Botany ,QK1-989 - Abstract
Potassium is an important essential element for plant growth and development. Long-term potassium deprivation can lead to a severe deficiency phenotype in plants. Interestingly, Phytolacca acinosa is a plant with an unusually high potassium content and can grow well and complete its lifecycle even in severely potassium deficient soil. In this study, we found that its stems and leaves were the main tissues for high potassium accumulation, and P. acinosa showed a strong ability of K+ absorption in roots and a large capability of potassium accumulation in shoots. Analysis of plant growth and physiological characteristics indicated that P. acinosa had an adaptability in a wide range of external potassium levels. To reveal the mechanism of K+ uptake and transport in the potassium-hyperaccumulator plant P. acinosa, K+ uptake-/transport-related genes were screened by transcriptome sequencing, and their expression profiles were compared between K+ starved plants and normal cultured plants. Eighteen members of HAK/KT/KUPs, ten members of AKTs, and one member of HKT were identified in P. acinosa. Among them, six HAKs, and two AKTs and PaHKT1 showed significantly different expression. These transporters might be coordinatively involved in K+ uptake/transport in P. acinosa and lead to high potassium accumulation in plant tissues. In addition, significantly changed expression of some ABC transporters indicated that ABC transporters might be important for K+ uptake and transport in P. acinosa under low K+ concentrations.
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- 2020
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19. Microcosmic modulation of the Co-N bonding structure improves the multi-functional electrocatalytic performance.
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Wenhui Deng, Tianjing Wu, Yufeng Wu, Fang Chen, Yansong Bai, Xiaoqing Zou, Mingjun Jing, Wentao Deng, Hongshuai Hou, and Xianyou Wang
- Abstract
Cobalt-based materials are regarded as greatly active and stable catalysts zinc-air batteries (ZABs). However, details of Co active units are particularly elusive, and it is notoriously difficult to implement precise control, impeding the further improvement of electrochemical performance. Herein, theoretical models of Co-Nx (x = 2 and 4) are systematically designed and studied; the Co-N2 model can effectively perfect the rate-determining steps for the oxygen reduction reaction (*O / *OH, 0.27 eV) and oxygen evolution reaction (*OOH / * + O2, 0.25 eV). On this basis, utilizing a pyrolysis-free route, the well-defined Co-N2 structure is precisely designed and constructed in the specified atomic configuration. The method proposes atomic precision to regulate the bonding type of M-N2 units (M = Fe, Cu, and Ni). As expected, co-poly(5,10,15,20-tetrakis(4-aminophenyl)porphyrin) with Co-N2 active units (Co-PTAPP) demonstrates a rapid kinetic process (34.7 mV dec-1), superior to that of the porphyrin organic covalent material with Co-N4 active centers (Co-POC), matching well with calculated results. In addition, a high-efficiency water uptake hydrogel (PVA-IL), with 1-hydroxylethy-3-methylimidazolium chloride (HOEtMImCl) as the hydrating agent, is efficiently synthesized. Applying optimized PVA-IL in flexible ZABs enables a long discharge time (500 min) at 4 mA cm
-2 , surpassing that of the PVA hydrogel. [ABSTRACT FROM AUTHOR]- Published
- 2024
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20. Optimization of cold plasma combined treatment process and its effect on the quality of Asian sea bass (Lates calcarifer) during refrigerated storage.
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Yuanyuan Wang, Xiaohan Sang, Zhicheng Cai, Lixian Zeng, Wentao Deng, Jianhao Zhang, Zhumao Jiang, and Jiamei Wang
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GIANT perch ,LOW temperature plasmas ,REFRIGERATED storage ,EUROPEAN seabass - Abstract
BACKGROUND: Cold plasma exhibits broad applicability in the realm of fish sterilization and preservation. The combination process of plasma-activated water and dielectric barrier discharge (PAW-DBD) was optimized, and its disinfection effects on bass fillets were studied. RESULTS: The best conditions for disinfection of PAW-DBD were as follows. Bass fillets were soaked in PAW for 150 s, and then treated by DBD system at 160 kV for 180 s. The total viable count (TVC) reduced by 1.68 log CFU g
-1 . On the 15th day of refrigerated storage, TVC of PAW-DBD group was 7.01 log CFU g-1 , while the PAW and DBD group exhibited a TVC of 7.02 and 7.01 log CFU g-1 on day 12; the TVC of the control group was 7.13 log CFU g-1 on day 6. The sensory score, water-holding capacity, and 2-thiobarbituric acid reactive substance values of the PAW-DBD group were significantly higher than those of PAW and DBD group (P < 0.05), whereas the TVC, Pseudomonas spp. count, and pH of the group were significantly lower (P < 0.05) during refrigerated storage. CONCLUSION: PAW-DBD treatment can enhance the disinfection effect, maintain good quality, and extend the storage period of bass fillets. [ABSTRACT FROM AUTHOR]- Published
- 2024
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21. Ultrahigh-speed graphene-based optical coherent receiver
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Hailong Zhou, Lei Ye, Wentao Deng, Xinyu Huang, Xi Xiao, Xiang Li, Zhibin Jiang, Xiaoyan Gao, Yu Yu, Xinliang Zhang, Lei Tong, Yilun Wang, Wang, Yilun [0000-0001-9416-2219], Jiang, Zhibin [0000-0002-0455-409X], Ye, Lei [0000-0001-5195-1867], Xiao, Xi [0000-0003-3696-877X], Zhang, Xinliang [0000-0001-8513-3328], and Apollo - University of Cambridge Repository
- Subjects
Ethernet ,Fibre optics and optical communications ,Science ,Optical communication ,General Physics and Astronomy ,General Biochemistry, Genetics and Molecular Biology ,Article ,Slot-waveguide ,46 Information and Computing Sciences ,4018 Nanotechnology ,40 Engineering ,Physics ,Nanophotonics and plasmonics ,Multidisciplinary ,business.industry ,Bandwidth (signal processing) ,Keying ,Integrated optics ,General Chemistry ,Optical properties and devices ,Modulation ,Optoelectronics ,Photonics ,business ,51 Physical Sciences ,Quadrature amplitude modulation - Abstract
Graphene-based photodetectors have attracted significant attention for high-speed optical communication due to their large bandwidth, compact footprint, and compatibility with silicon-based photonics platform. Large-bandwidth silicon-based optical coherent receivers are crucial elements for large-capacity optical communication networks with advanced modulation formats. Here, we propose and experimentally demonstrate an integrated optical coherent receiver based on a 90-degree optical hybrid and graphene-on-plasmonic slot waveguide photodetectors, featuring a compact footprint and a large bandwidth far exceeding 67 GHz. Combined with the balanced detection, 90 Gbit/s binary phase-shift keying signal is received with a promoted signal-to-noise ratio. Moreover, receptions of 200 Gbit/s quadrature phase-shift keying and 240 Gbit/s 16 quadrature amplitude modulation signals on a single-polarization carrier are realized with a low additional power consumption below 14 fJ/bit. This graphene-based optical coherent receiver will promise potential applications in 400-Gigabit Ethernet and 800-Gigabit Ethernet technology, paving another route for future high-speed coherent optical communication networks., Graphene-based photodetectors have many advantages for applications. Here, the authors demonstrate a high-speed optical coherent receiver for optical communications based on graphene-on-plasmonic slot waveguide photodetectors.
- Published
- 2021
22. Behavior of CFRP-Confined Sand-Based Material Columns under Axial Compression
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Li Guodong, Honglin Liu, Wentao Deng, Haitian Yan, and Wang Hongzhi
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chemistry.chemical_classification ,composite structure ,Materials science ,Polymers and Plastics ,Mixing (process engineering) ,Shell (structure) ,Organic chemistry ,General Chemistry ,Polymer ,Strain hardening exponent ,Fibre-reinforced plastic ,underground mines ,desert sand ,fiber-reinforced polymer ,Article ,QD241-441 ,chemistry ,high-water material ,Infill ,Bearing capacity ,Composite material ,Tube (container) - Abstract
This paper presents an innovative pumpable standing support designed for underground mines located in the arid and semi-arid deserts of the Gobi region with a shortage of water resources. The exterior shell of this pumpable standing support is made of carbon fiber-reinforced polymer (CFRP), while the infill material is a sand-based material (SBM). As the novel backfill material, SBM is the combination of high-water cementing material and desert sand. A series of experimental tests were conducted to obtain the mechanical response mechanism of this novel pumpable standing support under uniaxial compression. Test variables investigated in this research covered the water-to-powder ratio of the cementing material, the mixing amount of sand, and the thickness of the CFRP tube. Test results confirmed that the CFRP-confined SBM columns exhibited typical strain hardening behavior with the acceptable axial deformation. It was also demonstrated that using high-strength cementing material, a thicker CFRP tube, and a high mixing amount of sand effectively increased the bearing capacity of the CFRP-confined SBM column. Except for the exemplary structural behavior, the consumption of high-water cementing materials of the novel pumpable standing support is smaller than that of its counterparts made of pure cementing material, when specimens with the same mechanical performance are compared.
- Published
- 2021
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23. Data-driven learning how oncogenic gene expression locally alters heterocellular networks
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Anika Coolbaugh Pirkey, Audry Fernandez, Wentao Deng, Habibolla Latifizadeh, and David J. Klinke
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Modeling and simulation ,Tumor microenvironment ,Cell signaling ,Computer science ,Gene expression ,medicine ,Computational biology ,Carcinogenesis ,medicine.disease_cause ,Data-driven learning ,Expression (mathematics) ,Complement (complexity) ,Causal model - Abstract
Discovering and developing pharmaceutical drugs increasingly relies on mechanistic mathematical modeling and simulation. In immuno-oncology, models that capture causal relations among genetic drivers of oncogenesis, functional plasticity, and host immunity provide an important complement to wet experiments, given the cellular complexity and dynamics within the tumor microenvironment. Unfortunately, formulating such mechanistic cell-level models currently relies on hand curation by experts, which can bias how data is interpreted or the priority of drug targets. In modeling molecular-level networks, rules and algorithms have been developed to limit a priori biases in formulating mechanistic models. To realize an equivalent approach for cell-level networks, we combined digital cytometry with Bayesian network inference to generate causal models that link an increase in gene expression associated with oncogenesis with alterations in stromal and immune cell subsets directly from bulk transcriptomic datasets. To illustrate, we predicted how an increase in expression of Cell Communication Network factor 4 (CCN4/WISP1) altered the tumor microenvironment using data from patients diagnosed with breast cancer and melanoma. Network predictions were then tested using two immunocompetent mouse models for melanoma. In contrast to hand-curated approaches, we posit that combining digital cytometry with Bayesian network inference provides a less biased approach for elaborating mechanistic cell-level models directly from data.
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- 2020
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24. Therapeutic effect and adverse reaction of sorafenib in the treatment of advanced renal cancer
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Wei Jiang, Ning Li, Wentao Deng, Juhui Qiu, Qinglei Zhang, Dongjian Liu, Zaichun Yan, and Kejia Ding
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0301 basic medicine ,Sorafenib ,Cancer Research ,medicine.medical_specialty ,efficacy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,adverse reactions ,Adverse effect ,advanced renal cancer ,business.industry ,Incidence (epidemiology) ,Therapeutic effect ,Cancer ,Articles ,medicine.disease ,targeted therapy ,Rash ,030104 developmental biology ,Hair loss ,Oncology ,030220 oncology & carcinogenesis ,sorafenib ,Liver function ,medicine.symptom ,business ,medicine.drug - Abstract
Efficacy and safety of sorafenib in patients with advanced renal cancer were evaluated. Seventy-four patients with advanced renal cancer treated with sorafenib + interferon from January 2010 to August 2013 were included as the observation group. Another 53 renal cancer patients treated with interferon alone were included in the control group. Clinical data of those patients were retrospectively analyzed. Treatment plan: initial dose was 400 mg, twice a day. Additionally, patients in the interferon group were treated with another 300 MU every other day. Efficacy was evaluated according to RECIST criteria, and progression-free survival (PFS), overall survival (OS), and incidence of adverse reactions were recorded. In the observation group, a median OS was 15.3 months (range, 9-60 months), and a median PFS was 8.2 months (range, 2-36 months). There were 4 cases of complete remission (CR) (5.41%), 16 cases of partial remission (PR) (21.62%), 42 cases of stable disease (SD) (56.76%), 12 cases of disease progression (16.22%), and disease control rate (DCR) was 83.78% (62 cases). In the control group, median OS time was 12.5 months (range, 8-60 months), and the median PFS time was 9.3 months (range, 2-40 months). There were 2 cases of CR (3.77%), 11 cases of PR (20.75%), 20 cases of SD (37.74%), 20 cases of disease progression (37.74%), and DCR was 62.26% (33 cases). Disease control rate in the observation group was significantly higher than that in the control group (P
- Published
- 2018
25. Interleukin-12 elicits a non-canonical response in B16 melanoma cells to enhance survival
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David J. Klinke, Christina N. Byrne-Hoffman, Wentao Deng, Owen McGrath, Peng Wang, and Yon Rojanasakul
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0301 basic medicine ,Skin Neoplasms ,medicine.medical_treatment ,Cell ,Melanoma, Experimental ,lcsh:Medicine ,Biochemistry ,Mice ,0302 clinical medicine ,Cytotoxic T cell ,STAT4 ,0303 health sciences ,Chemistry ,lcsh:Cytology ,Receptors, Interleukin-12 ,PI3K-AKT signaling ,Interleukin-12 ,Cell biology ,Immunosurveillance ,Cytokine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Intracellular signaling ,Interleukin 12 ,Phosphorylation ,JAK-STAT signaling ,Intracellular ,Cell Survival ,Biology ,03 medical and health sciences ,Immune system ,Non-canonical ,medicine ,Animals ,Humans ,Secretion ,lcsh:QH573-671 ,Antigen-presenting cell ,Protein kinase B ,Molecular Biology ,030304 developmental biology ,Tumor microenvironment ,Research ,Interleukins ,lcsh:R ,Cell Biology ,030104 developmental biology ,Cell culture ,Proto-Oncogene Proteins c-akt - Abstract
Background Oncogenesis rewires signaling networks to confer a fitness advantage to malignant cells. For instance, the B16F0 melanoma cell model creates a cytokine sink for Interleukin-12 (IL-12) to deprive neighboring cells of this important anti-tumor immune signal. While a cytokine sink provides an indirect fitness advantage, does IL-12 provide an intrinsic advantage to B16F0 cells? Methods Acute in vitro viability assays were used to compare the cytotoxic effect of imatinib on a melanoma cell line of spontaneous origin (B16F0) with a normal melanocyte cell line (Melan-A) in the presence of IL-12. The results were analyzed using a mathematical model coupled with a Markov Chain Monte Carlo approach to obtain a posterior distribution in the parameters that quantified the biological effect of imatinib and IL-12. Intracellular signaling responses to IL-12 were compared using flow cytometry in 2D6 cells, a cell model for canonical signaling, and B16F0 cells, where potential non-canonical signaling occurs. Bayes Factors were used to select among competing signaling mechanisms that were formulated as mathematical models. Analysis of single cell RNAseq data from human melanoma patients was used to explore generalizability. Results Functionally, IL-12 enhanced the survival of B16F0 cells but not normal Melan-A melanocytes that were challenged with a cytotoxic agent. Interestingly, the ratio of IL-12 receptor components (IL12RB2:IL12RB1) was increased in B16F0 cells. A similar pattern was observed in human melanoma. To identify a mechanism, we assayed the phosphorylation of proteins involved in canonical IL-12 signaling, STAT4, and cell survival, Akt. In contrast to T cells that exhibited a canonical response to IL-12 by phosphorylating STAT4, IL-12 stimulation of B16F0 cells predominantly phosphorylated Akt. Mechanistically, the differential response in B16F0 cells is explained by both ligand-dependent and ligand-independent aspects to initiate PI3K-AKT signaling upon IL12RB2 homodimerization. Namely, IL-12 promotes IL12RB2 homodimerization with low affinity and IL12RB2 overexpression promotes homodimerization via molecular crowding on the plasma membrane. Conclusions The data suggest that B16F0 cells shifted the intracellular response to IL-12 from engaging immune surveillance to favoring cell survival. Identifying how signaling networks are rewired in model systems of spontaneous origin can inspire therapeutic strategies in humans. Plain english summary Interleukin-12 is a key cytokine that promotes anti-tumor immunity, as it is secreted by antigen presenting cells to activate Natural Killer cells and T cells present within the tumor microenvironment. Thinking of cancer as an evolutionary process implies that an immunosuppressive tumor microenvironment could arise during oncogenesis by interfering with endogenous anti-tumor immune signals, like IL-12. Previously, we found that B16F0 cells, a cell line derived from a spontaneous melanoma, interrupts this secreted heterocellular signal by sequestering IL-12, which provides an indirect fitness advantage. Normally, IL-12 signals via a receptor comprised of two components, IL12RB1 and IL12RB2, that are expressed in a 1:1 ratio and activates STAT4 as a downstream effector. Here, we report that B16F0 cells gain an intrinsic advantage by rewiring the canonical response to IL-12 to instead initiate PI3K-AKT signaling, which promotes cell survival. The data suggest a model where overexpressing one component of the IL-12 receptor, IL12RB2, enables melanoma cells to shift the functional response via both IL-12-mediated and molecular crowding-based IL12RB2 homodimerization. To explore the generalizability of these results, we also found that the expression of IL12RB2:IL12RB1 is similarly skewed in human melanoma based on transcriptional profiles of melanoma cells and tumor-infiltrating lymphocytes.
- Published
- 2019
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26. Antenna-integrated silicon–plasmonic graphene sub-terahertz emitter
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Yu Yu, Yilun Wang, Shixing Yuan, Wentao Deng, Zhibin Jiang, Xiaojun Wu, Xinliang Zhang, Ziwei Wang, Ruolan Wang, Qizhi Yan, and Liao Chen
- Subjects
Materials science ,Computer Networks and Communications ,business.industry ,Graphene ,Terahertz radiation ,Photodetector ,Physics::Optics ,Atomic and Molecular Physics, and Optics ,law.invention ,TA1501-1820 ,law ,Broadband ,Bandwidth (computing) ,Optoelectronics ,Applied optics. Photonics ,Antenna (radio) ,business ,Plasmon ,Common emitter - Abstract
Photo-mixing with its advantages of ultra-large bandwidth and precise tunability has emerged as an important technique for terahertz (THz) wave generation. Recently, graphene photodetectors exhibiting a large bandwidth are expected to further boost the development of integrated THz emitters. Here, we fabricate a sub-THz emitter based on a large-bandwidth silicon–plasmonic graphene (SPG) photodetector integrated with a broadband rounded bow-tie THz antenna. The SPG sub-THz emitter is experimentally demonstrated to emit sub-THz waves with a radiation spectrum from 50 to 300 GHz. A maximum sub-THz emission power of 5.4 nW is obtained at 145 GHz with only 3 mW input light power. The SPG sub-THz emitter can be fabricated by a CMOS-compatible process, which offers enormous opportunities for its use in a variety of THz applications.
- Published
- 2021
27. Electronic Effect and Regiochemistry of Substitution in Pre-sodiation Chemistry.
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Kangyu Zou, Zirui Song, Huanqing Liu, Ying Wang, Massoudi, Abouzar, Wentao Deng, Hongshuai Hou, Guoqiang Zou, and Xiaobo Ji
- Published
- 2021
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28. Liquid Alloying Na-K for Sodium Metal Anodes.
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Cheng Liu, Hongyi Chen, Wentao Deng, Jun Chen, Ye Tian, Xu Gao, Xinglan Deng, Shouyi Yi, Shuo Li, Libao Chen, Anqiang Pan, Jianmin Ma, Hongsuai Hou, Guoqiang Zou, Silvester, Debbie S., and Xiaobo Ji
- Published
- 2021
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29. WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial–mesenchymal transition
- Author
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Sarah L. McLaughlin, Wentao Deng, Audry Fernandez, and David J. Klinke
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,Melanoma, Experimental ,Mice, SCID ,Biochemistry ,CCN Intercellular Signaling Proteins ,03 medical and health sciences ,Mice ,Mice, Inbred NOD ,Proto-Oncogene Proteins ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,Molecular Biology ,Protein kinase B ,Regulation of gene expression ,Tumor microenvironment ,WNT1-inducible-signaling pathway protein 1 ,030102 biochemistry & molecular biology ,Chemistry ,Melanoma ,Wnt signaling pathway ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,HEK293 Cells ,Gene Knockdown Techniques ,SNAI1 ,Cancer research ,NIH 3T3 Cells ,Snail Family Transcription Factors ,Signal Transduction - Abstract
Besides intrinsic changes, malignant cells also release soluble signals that reshape their microenvironment. Among these signals is WNT1-inducible signaling pathway protein 1 (WISP1), a secreted matricellular protein whose expression is elevated in several cancers, including melanoma, and is associated with reduced survival of patients diagnosed with primary melanoma. Here, we found that WISP1 knockout increases cell proliferation and represses wound healing, migration, and invasion of mouse and human melanoma cells in multiple in vitro assays. Metastasis assays revealed that WISP1 knockout represses tumor metastasis of B16F10 and YUMM1.7 melanoma cells in both C57BL/6Ncrl and NOD-scid IL2Rγ(null) (NSG) mice. WT B16F10 cells having an invasion phenotype in a transwell assay possessed a gene expression signature similar to that observed in the epithelial–mesenchymal transition (EMT), including E-cadherin repression and fibronectin and N-cadherin induction. Upon WISP1 knockout, expression of these EMT signature genes went in the opposite direction in both mouse and human cell lines, and EMT-associated gene expression was restored upon exposure to media containing WISP1 or to recombinant WISP1 protein. In vivo, Wisp1 knockout–associated metastasis repression was reversed by the reintroduction of either WISP1 or snail family transcriptional repressor 1 (SNAI1). Experiments testing EMT gene activation and inhibition with recombinant WISP1 or kinase inhibitors in B16F10 and YUMM1.7 cells suggested that WISP1 activates AKT Ser/Thr kinase and that MEK/ERK signaling pathways shift melanoma cells from proliferation to invasion. Our results indicate that WISP1 present within the tumor microenvironment stimulates melanoma invasion and metastasis by promoting an EMT-like process.
- Published
- 2019
30. CCN4 shifts melanoma cells from a fragile proliferative state to a resilient metastatic state
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Wentao Deng, Audry Fernandez, Sarah L. McLaughlin, and David J. Klinke
- Subjects
0303 health sciences ,Tumor microenvironment ,Cell signaling ,Cell growth ,Melanoma ,Matricellular protein ,Biology ,medicine.disease ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell culture ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Signal transduction ,030304 developmental biology - Abstract
While deregulated intracellular signaling initiates melanoma, intercellular crosstalk within the tumor microenvironment, often coordinated by soluble factors, is essential for melanoma progression and metastasis. One such secreted matricellular protein, cellular communication network factor 4 (CCN4), stimulates metastasis in other malignancies. Here, we report that CCN4 expression is associated progressively with reduced overall survival in patients with primary melanomas. To reveal the roles of CCN4 in melanoma progression, we used mouse melanoma models and knocked outCcn4using a homology-directed repair CRISPR/CAS9 system to generate pools ofCcn4-knockout cells.In vitroassays supported previous findings using clones generated using a double nickase-based CRISPR/CAS9 system that CCN4 promoted an epithelial – mesenchymal-like transition in melanoma cells and stimulated invasion and metastasis. We also found that, whileCcn4knockout enhanced cell growth in optimal 2D culture conditions, the knockout suppressed certain cell survival signaling pathways and rendered cells less resistant to stress conditions. Tumor cell growth assays at sub-optimal conditionsin vitro, quantitative analysis of tumor growth assaysin vivo,and transcriptomics analysis of human melanoma cell lines suggested that CCN4 repressed cell growth and simultaneously enhanced cell survival. The collective role of CCN4 suggests a potential therapeutic target for limiting metastatic invasion in melanoma and a biomarker for metastatic potential.
- Published
- 2018
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31. WNT1 Inducible Signaling Pathway Protein 1 (WISP1) stimulates melanoma cell invasion and metastasis by promoting epithelial – mesenchymal transition
- Author
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Audry Fernandez, Sarah L. McLaughlin, David J. Klinke, and Wentao Deng
- Subjects
0303 health sciences ,Tumor microenvironment ,WNT1-inducible-signaling pathway protein 1 ,Chemistry ,Cell growth ,Melanoma ,Matricellular protein ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,SNAI1 ,Cancer research ,medicine ,Epithelial–mesenchymal transition ,Protein kinase B ,030304 developmental biology - Abstract
Besides intrinsic changes, malignant cells release soluble signals to reshape their microenvironment. Among the signaling factors is WNT1 inducible signaling pathway protein 1 (WISP1), a secreted matricellular protein that is elevated in a variety of cancers including melanoma and is associated with reduced overall survival of patients diagnosed with primary melanoma. In this work, we found thatWISP1knockout both increased cell proliferation and repressed wound healing, migration and invasion of mouse and human melanoma cells in an ensemble ofin vitroassays.In vivometastasis assays showed that WISP1 knockout repressed tumor metastasis in both C57BL/6Ncrl and NOD-scid IL2Rgammanull (NSG) mice with B16F10 and YUMM1.7 melanoma cells. Mechanistically, B16F10 cells that invaded in a transwell assay possessed a gene expression signature similar to Epithelial - Mesenchymal Transition (EMT), including coincident repression of E-cadherin and induction of fibronectin and N-cadherin. Upon WISP1 knockout, these EMT signature genes went in opposite directions in both mouse and human cell lines and were rescued by media containing WISP1 or recombinant WISP1 protein.In vivo,metastasis repression by WISP1 knockout was reversed by the reintroduction of either WISP1 or SNAI1. A set of EMT gene activation and inhibition experiments using recombinant WISP1 or kinase inhibitors in B16F10 and YUMM1.7 cells suggested that WISP1 activates Akt and MAP kinase signaling pathways to shift melanoma cells from a proliferative to invasive phenotype. Collectively, the results supported a model that WISP1 within the tumor microenvironment stimulates melanoma invasion and metastasis by promoting an EMT-like process.
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- 2018
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32. Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo
- Author
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Hailin Tan, Yuefeng Jia, Shaoting Wang, Wentao Deng, Juhui Qiu, Jiru Lu, Zhi Yuan, and Ruqiang Zheng
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Vascular Endothelial Growth Factor A ,Pharmaceutical Science ,Apoptosis ,Biocompatible Materials ,02 engineering and technology ,01 natural sciences ,Polyethylene Glycols ,chemistry.chemical_compound ,Drug Delivery Systems ,International Journal of Nanomedicine ,Neoplasms ,Drug Discovery ,Fluorescence microscope ,Original Research ,Drug Carriers ,Mice, Inbred BALB C ,Chemistry ,Oxides ,General Medicine ,021001 nanoscience & nanotechnology ,Human serum albumin ,Paclitaxel ,human serum albumin ,Drug delivery ,graphene oxide ,Graphite ,0210 nano-technology ,Drug carrier ,medicine.drug ,Biocompatibility ,Cell Survival ,Biophysics ,Mice, Nude ,Bioengineering ,010402 general chemistry ,Biomaterials ,photothermal-triggered tumor therapy ,In vivo ,Albumins ,Cell Line, Tumor ,medicine ,Animals ,Humans ,tumor targeting ,Organic Chemistry ,Hyperthermia, Induced ,Phototherapy ,Photothermal therapy ,0104 chemical sciences ,Drug Liberation ,Nanoparticles ,Albumin-Bound Paclitaxel - Abstract
Wentao Deng,1,* Juhui Qiu,1,* Shaoting Wang,1 Zhi Yuan,1 Yuefeng Jia,2 Hailin Tan,2 Jiru Lu,1 Ruqiang Zheng1 1Department of Urinary Surgery, Dongying People’s Hospital, Dongying, 2Department of Urinary Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China *These authors contributed equally tothis work Abstract: In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment. Keywords: paclitaxel, graphene oxide, human serum albumin, tumor targeting, photothermal-triggered tumor therapy
- Published
- 2018
33. Azetidinium lead iodide for perovskite solar cells
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Joel Troughton, Petra J. Cameron, Ralf G. Niemann, M. S. Islam, Wentao Deng, Samuel Pering, Simon E. Lewis, Trystan Watson, Paul R. Raithby, Alison B. Walker, Federico Brivio, Peter S. Kubiak, Florence E. Jeffrey, Dibyajyoti Ghosh, and Andrew L. Johnson
- Subjects
Solar cells ,Band gap ,Inorganic chemistry ,Iodide ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,7. Clean energy ,Azetidinium ,Photovoltaics ,General Materials Science ,Thin film ,perovskite ,Perovskite (structure) ,chemistry.chemical_classification ,Thin Films ,Renewable Energy, Sustainability and the Environment ,Chemistry ,business.industry ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Improved performance ,Formamidinium ,0210 nano-technology ,business - Abstract
Hybrid organic–inorganic perovskites have been established as good candidate materials for emerging photovoltaics, with device efficiencies of over 22% being reported. There are currently only two organic cations, methylammonium and formamidinium, which produce 3D perovskites with band gaps suitable for photovoltaic devices. Numerous computational studies have identified azetidinium as a potential third cation for synthesizing organic–inorganic perovskites, but to date no experimental reports of azetidinium containing perovskites have been published. Here we prepare azetidinium lead iodide for the first time. Azetidinium lead iodide is a stable, bright orange material which does not appear to form a 3D or a 2D perovskite. It was successfully used as the absorber layer in solar cells. We also show that it is possible to make mixed cation devices by adding the azetidinium cation to methylammonium lead iodide. Computational studies show that the substitution of up to 5% azetidinium into the methylammonium lead iodide is energetically favourable and that phase separation does not occur at these concentrations. Mixed azetidinium–methylammonium cells show improved performance and reduced hysteresis compared to methylammonium lead iodide cells.
- Published
- 2017
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34. Quantifying spontaneous metastasis in a syngeneic mouse melanoma model using real time PCR
- Author
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David J. Klinke, Wentao Deng, and Sarah L. McLaughlin
- Subjects
0301 basic medicine ,Lung Neoplasms ,Melanoma, Experimental ,Mice, SCID ,Biology ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Article ,Analytical Chemistry ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Mice, Inbred NOD ,Cell Line, Tumor ,Electrochemistry ,medicine ,Environmental Chemistry ,Bioluminescence imaging ,Animals ,Luciferase ,Neoplasm Metastasis ,Spectroscopy ,030304 developmental biology ,0303 health sciences ,Melanoma ,biology.organism_classification ,medicine.disease ,Extravasation ,Mice, Inbred C57BL ,030104 developmental biology ,Real-time polymerase chain reaction ,Cell culture ,Lentivirus ,Cancer research ,030217 neurology & neurosurgery - Abstract
Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells. In this work, we developed an approach for quantifying spontaneous metastasis in the syngeneic mouse B16 system using real time PCR. We first transduced B16 cells with lentivirus expressing firefly luciferase Luc2 gene for bioluminescence imaging. Next, we developed a real time quantitative PCR (qPCR) method for the detection of luciferase-expressing, metastatic tumor cells in mouse lungs and other organs. To illustrate the approach, we quantified lung metastasis in both spontaneous and experimental scenarios using B16F0 and B16F10 cells in C57BL/6Ncrl and NOD-Scid Gamma (NSG) mice. We tracked B16 melanoma metastasis with both bioluminescence imaging and qPCR, which were found to be self-consistent. Using this assay, we can quantitatively detect one Luc2 positive tumor cells out of 104 tissue cells, which corresponds to a metastatic burden of 1.8x104 metastatic cells per whole mouse lung. More importantly, the qPCR method was at least a factor of 10 more sensitive in detecting metastatic cell dissemination and should be combined with bioluminescence imaging as a high-resolution, end-point method for final metastatic cell quantitation. Given the rapid growth of primary tumors in many mouse models, assays with improved sensitivity can provide better insight into biological mechanisms that underpin tumor metastasis.
- Published
- 2017
- Full Text
- View/download PDF
35. Manganese-based layered oxide cathodes for sodium ion batteries.
- Author
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Huanqing Liu, Wentao Deng, Xu Gao, Jun Chen, Shouyi Yin, Li Yang, Guoqiang Zou, Hongshuai Hou, and Xiaobo Ji
- Published
- 2020
- Full Text
- View/download PDF
36. WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial-mesenchymal transition.
- Author
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Wentao Deng, Fernandez, Audry, McLaughlin, Sarah L., and Klinke II, David J.
- Subjects
- *
CHO cell , *MELANOMA , *GENETIC regulation , *RECOMBINANT proteins , *METASTASIS , *CANCER invasiveness - Abstract
Besides intrinsic changes, malignant cells also release soluble signals that reshape their microenvironment. Among these signals is WNT1-inducible signaling pathway protein 1 (WISP1), a secreted matricellular protein whose expression is elevated in several cancers, including melanoma, and is associated with reduced survival of patients diagnosed with primary melanoma. Here, we found that WISP1 knockout increases cell proliferation and represses wound healing, migration, and invasion of mouse and human melanoma cells in multiple in vitro assays. Metastasis assays revealed that WISP1 knockout represses tumor metastasis of B16F10 and YUMM1.7 melanoma cells in both C57BL/6Ncrl and NOD-scid IL2Rγnull (NSG) mice. WT B16F10 cells having an invasion phenotype in a transwell assay possessed a gene expression signature similar to that observed in the epithelial-mesenchymal transition (EMT), including E-cadherin repression and fibronectin and N-cadherin induction. Upon WISP1 knockout, expression of these EMT signature genes went in the opposite direction in both mouse and human cell lines, and EMT-associated gene expression was restored upon exposure to media containing WISP1 or to recombinant WISP1 protein. In vivo, Wisp1 knockout-associated metastasis repression was reversed by the reintroduction of either WISP1 or snail family transcriptional repressor 1 (SNAI1). Experiments testing EMT gene activation and inhibition with recombinant WISP1 or kinase inhibitors in B16F10 and YUMM1.7 cells suggested that WISP1 activatesAKTSer/Thr kinase and that MEK/ERK signaling pathways shift melanoma cells from proliferation to invasion. Our results indicate that WISP1 present within the tumor microenvironment stimulates melanoma invasion and metastasis by promoting an EMT-like process. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
37. Continuous low temperature synthesis of MAPbX3 perovskite nanocrystals in a flow reactor.
- Author
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Xinxing Liang, Baker, Robert W., Kejun Wu, Wentao Deng, Ferdani, Dominic, Kubiak, Peter S., Marken, Frank, Torrente-Murciano, Laura, and Cameron, Petra J.
- Published
- 2018
- Full Text
- View/download PDF
38. Mitogen-Activated Protein Kinases Activate the Nuclear Localization Sequence of Human Papillomavirus Type 11 E1 DNA Helicase To Promote Efficient Nuclear Import▿
- Author
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Thomas R. Broker, Biing Yuan Lin, Jei-Hwa Yu, Wentao Deng, and Louise T. Chow
- Subjects
MAPK/ERK pathway ,Immunology ,Amino Acid Motifs ,Nuclear Localization Signals ,Active Transport, Cell Nucleus ,Virus Replication ,Microbiology ,Models, Biological ,Cell Line ,Viral Proteins ,Virology ,Chlorocebus aethiops ,Animals ,Humans ,Nuclear export signal ,Protein kinase A ,Protein Kinase Inhibitors ,Bovine papillomavirus ,Cell Nucleus ,Binding Sites ,Mitogen-Activated Protein Kinase 3 ,biology ,Kinase ,Human papillomavirus 11 ,DNA Helicases ,JNK Mitogen-Activated Protein Kinases ,biology.organism_classification ,Molecular biology ,Virus-Cell Interactions ,DNA-Binding Proteins ,Microscopy, Fluorescence ,Insect Science ,Mitogen-activated protein kinase ,biology.protein ,Mutagenesis, Site-Directed ,Nuclear transport ,Mitogen-Activated Protein Kinases ,Nuclear localization sequence - Abstract
Human and animal papillomavirus DNA replicates as multicopy nuclear plasmids. Replication requires two viral proteins, the origin-recognition protein E2 and the replicative DNA helicase E1. Using genetic, biochemical, and immunofluorescence assays, we demonstrated that efficient nuclear import of the human papillomavirus (HPV) type 11 E1 protein depends on a codominant bipartite nuclear localization sequence (NLS) and on phosphorylation of the serine residues S89 and S93 by the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase, and c-Jun N-terminal protein kinase. The NLS and the MAPK substrates are located within a 50-amino-acid-long peptide near the amino terminus, previously designated the localization regulatory region (LRR). The downstream NLS overlaps the cyclin-binding motif RRL, which is necessary for phosphorylation by the cyclin-dependent kinases to inactivate a dominant nuclear export sequence, also in the LRR. Alanine mutations of the MAPK substrates significantly impaired nuclear import, whereas phospho-mimetic mutations partially restored nuclear import. We further identified two MAPK docking motifs near the C terminus of E1 that are conserved among E1 proteins of many HPVs and bovine papillomavirus type 1. Mutations of these MAPK docking motifs or addition of specific MAPK inhibitors significantly reduced nuclear import. Interestingly, a fraction of the NLS-minus E1 protein was cotransported with the E2 protein into the nucleus and supported transient viral DNA replication. In contrast, E1 proteins mutated in the MAPK docking motifs were completely inactive in transient replication, an indication that additional properties were adversely affected by those changes.
- Published
- 2007
39. Solubility of Carbon Dioxide in LiF-Li2CO3 Molten Salt System.
- Author
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Zhongning Shi, Wentao Deng, Xiaowen Song, Xianwei Hu, Bingliang Gao, and Zhaowen Wang
- Subjects
- *
CARBON dioxide solubility , *LITHIUM fluoride , *FUSED salts , *LITHIUM carbonate , *TEMPERATURE effect , *EXOTHERMIC reactions - Abstract
The solubility of carbon dioxide in a LiF-Li2CO3 molten salt system was determined using a pressure differential method. With increasing holding temperature, the solubility of CO2 in LiF-Li2CO3 melts decreases rapidly. The influence of the alkali metal fluoride of XF(X = K, Na) content from 5% to 25% on the CO2 solubility was considered. The CO2 solubility in LiF-Li2CO3-XF melts decreased with increasing temperature and concentration of XF. The calculated thermodynamic data for CO2 dissolved in these melts revealed that the reaction between CO2 and a carbonate ion was exothermic. At 630 °C, KF decreased the CO2 solubility more effectively than NaF. When the mole fraction of LiF was 50% in LiF-Li2CO3, the CO2 solubility reached a maximum of 6.8 x 10-4 (molCO2/molmelt) at 640 °C. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
40. Cyclin/CDK Regulates the Nucleocytoplasmic Localization of the Human Papillomavirus E1 DNA Helicase.
- Author
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Wentao Deng, Biing Yuan Lin, Ge Jin, Wheeler, Crystal G., Tianlin Ma, Harper, J. Wade, Broker, Thomas R., and Chow, Louise T.
- Subjects
- *
PAPILLOMAVIRUSES , *ONCOGENIC DNA viruses , *ONCOGENIC viruses , *DNA viruses , *DNA helicases - Abstract
Cyclin-dependent kinases (CDKs) play key roles in eukaryotic DNA replication and cell cycle progression. Phosphorylation of components of the preinitiation complex activates replication and prevents reinitiation. One mechanism is mediated by nuclear export of critical proteins. Human papillomavirus (HPV) DNA replication requires cellular machinery in addition to the viral replicative DNA helicase E1 and origin recognition protein E2. E1 phosphorylation by cyclin/CDK is critical for efficient viral DNA replication. We now show that E1 is phosphorylated by CDKs in vivo and that phosphorylation regulates its nucleocytoplasmic localization. We identified a conserved regulatory region for localization which contains a dominant leucine-rich nuclear export sequence (NES), the previously defined cyclin binding motif, three serine residues that are CDK substrates, and a putative bipartite nuclear localization sequence. We show that E1 is exported from the nucleus by a CRM1-dependent mechanism unless the NES is inactivated by CDK phosphorylation. Replication activities of E1 phosphorylation site mutations are reduced and correlate inversely with their increased cytoplasmic localization. Nuclear localization and replication activities of most of these mutations are enhanced or restored by mutations in the NES. Collectively, our data demonstrate that CDK phosphorylation controls E1 nuclear localization to support viral DNA amplification. Thus, HPV adopts and adapts the cellular regulatory mechanism to complete its reproductive program. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
41. MRNA Splicing Regulates Human Papillomavirus Type 11 E1 Protein Production and DNA Replication.
- Author
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Wentao Deng, Ge Jin, Biing-Yuan Lin, Van Tine, Brian A., Broker, Thomas R., and Chow, Louise T.
- Subjects
- *
PAPILLOMAVIRUSES , *PLASMIDS , *PROTEINS , *MESSENGER RNA - Abstract
Shows the fusion of fluorescent protein to the N terminus of human papillomavirus type 11 (HPV-11) E1 in a plasmid expressing E1 alone and in a replicon that also expressed E2 from the native sequence context of the viral genome. Cell cultures and transfections; Transient replication assays; Antibodies and Western blotting; Multiple intragenic splices within the E1 transcript reduce the expression of E1 and mRNA and protein.
- Published
- 2003
- Full Text
- View/download PDF
42. B16F0 melanoma exosomes deliver a unique and complex biological payload that includes Ptpn11 to suppress T lymphocyte function
- Author
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David J. Klinke, Emily Chambers McGinley, Wentao Deng, and Yueting Wu
- Subjects
Pharmacology ,Cancer Research ,business.industry ,Melanoma ,Immunology ,T lymphocyte ,medicine.disease_cause ,medicine.disease ,Bioinformatics ,Somatic evolution in cancer ,Microvesicles ,Cell biology ,PTPN11 ,Oncology ,Antigen ,Poster Presentation ,medicine ,Molecular Medicine ,Immunology and Allergy ,Carcinogenesis ,business ,Function (biology) - Abstract
Meeting abstracts Host immunity is coordinated through a complex network of intercellular communication. Similar to the sculpting of tumor antigens during oncogenesis, a related hypothesis is that proteins secreted by malignant cells are shaped by somatic evolution. Malignant cells that then emerge
- Full Text
- View/download PDF
43. Mitogen-Activated Protein Kinases Activate the Nuclear Localization Sequence of Human Papillomavirus Type 11 E1 DNA Helicase To Promote Efficient Nuclear Import.
- Author
-
Jei-Hwa Yu, Biing Yuan Lin, Wentao Deng, Broker, Thomas R., and Chow, Louise T.
- Subjects
- *
PAPILLOMAVIRUS diseases , *DNA , *PLASMIDS , *VIRAL proteins , *PHOSPHORYLATION , *PROTEINS - Abstract
Human and animal papillomavirus DNA replicates as multicopy nuclear plasmids. Replication requires two viral proteins, the origin-recognition protein E2 and the replicative DNA helicase E1. Using genetic, biochemical, and immunofluorescence assays, we demonstrated that efficient nuclear import of the human papillomavirus (HPV) type 11 E1 protein depends on a codominant bipartite nuclear localization sequence (NLS) and on phosphorylation of the serine residues S89 and S93 by the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase, and c-Jun N-terminal protein kinase. The NLS and the MAPK substrates are located within a 50-amino-acid-long peptide near the amino terminus, previously designated the localization regulatory region (LRR). The downstream NLS overlaps the cyclin-binding motif RRL, which is necessary for phosphorylation by the cyclin-dependent kinases to inactivate a dominant nuclear export sequence, also in the LRR. Alanine mutations of the MAPK substrates significantly impaired nuclear import, whereas phospho-mimetic mutations partially restored nuclear import. We further identified two MAPK docking motifs near the C terminus of E1 that are conserved among E1 proteins of many HPVs and bovine papillomavirus type 1. Mutations of these MAPK docking motifs or addition of specific MAPK inhibitors significantly reduced nuclear import. Interestingly, a fraction of the NLS-minus E1 protein was cotransported with the E2 protein into the nucleus and supported transient viral DNA replication. In contrast, E1 proteins mutated in the MAPK docking motifs were completely inactive in transient replication, an indication that additional properties were adversely affected by those changes. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
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