Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmid...Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor progression.The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.It can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells.Therefore,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor outcome.Thus,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.展开更多
事故隐患分类能够直观反映企业安全生产管理的薄弱点,同时将直接决定企业优化安全管理工作的方向。油田安全生产过程中,隐患种类多,数据量大,单纯依赖人工方式分类及管理效率较低,且难以发掘数据中蕴含的潜在规律。基于油田安全生产的...事故隐患分类能够直观反映企业安全生产管理的薄弱点,同时将直接决定企业优化安全管理工作的方向。油田安全生产过程中,隐患种类多,数据量大,单纯依赖人工方式分类及管理效率较低,且难以发掘数据中蕴含的潜在规律。基于油田安全生产的需求及事故隐患特征,提出了一种基于BERT-BiLSTM的分类模型,用于油田安全生产隐患文本的主题自动分类,通过基于Transformer的双向编码器表示(bidirectionalencoder representations from Transformer,BERT)模型提取输入文本的字符级特征,生成全局文本信息的向量表示,再通过双向长短时记忆网络(bi-directional long short-term memory,BiLSTM)模型对局部关键信息和上下文深层次特征进行特征提取,进而通过Softmax激活函数进行概率计算得到分类结果。通过与传统分类方法的比较表明,BERT-BiLSTM分类模型在加权平均准确率、加权平均召回率和加权平均F_(1)等指标方面均有所改善,模型与油田企业现有安全管理信息系统的有机融合将为进一步提升油田企业的事故隐患管理针对性,推动企业安全管理从事后被动反应向事前主动预防转变提供重要的技术支撑。展开更多
Strain is a powerful tool to engineer the band structure of bilayer phosphorene.The band gap can be decreased by vertical tensile strain or in-plane compressive strain.At a critical strain,the gap is closed and the bi...Strain is a powerful tool to engineer the band structure of bilayer phosphorene.The band gap can be decreased by vertical tensile strain or in-plane compressive strain.At a critical strain,the gap is closed and the bilayer phosphorene is turn to be a semi-Dirac semimetal material.If the strain is stronger than the criterion,a band-inversion occurs and it re-happens when the strain is larger than another certain value.For the zigzag bilayer phosphorene ribbon,there are two edge band dispersions and each dispersion curve represents two degenerate edge bands.When the first band-inversion happens,one of the edge band dispersion disappears between the band-cross points while the other survives,and the latter will be eliminated between another pair of band-cross points of the second band-inversion.The optical absorption of bilayer phosphorene is highly polarized along armchair direction.When the strain is turn on,the optical absorption edge changes.The absorption rate for armchair polarized light is decreased by gap shrinking,while that for zigzag polarized light increases.The bandtouch and band-inversion respectively result in the sublinear and linear of absorption curve versus light frequency in low frequency limit.展开更多
As the base oil of the current flat-rheology synthetic drilling fluid is high in cost and not renewable, the biodiesel-based flat-rheology drilling fluid with low-cost, environmental protection and renewable advantage...As the base oil of the current flat-rheology synthetic drilling fluid is high in cost and not renewable, the biodiesel-based flat-rheology drilling fluid with low-cost, environmental protection and renewable advantage was studied. Based on the optimization of raw materials, a cheap, environment-friendly biodiesel of soybean oil ethyl ester with good fluidity at low temperature was selected as the base oil. By selecting high oil-water ratio and introducing cationic surfactant into the auxiliary emulsifier, the thickening of biodiesel-based emulsion caused by hydrolysis and saponification after high-temperature aging was effectively eliminated. The organoclay prepared with cationic modifier of hexadecyl trimethyl ammonium chloride was used to improve the rheologic properties, stability and fluid loss of the drilling fluid while preventing low-temperature thickening. A flat-rheology modifier was synthesized with dimer fatty acid and cocoanut fatty acid diethanolamide, which could form strong network structure in the biodiesel-based drilling fluid to adjust effectively rheological properties of the drilling fluid. A biodiesel-based flat-rheology drilling fluid system with the density of 1.2 g/cm^(3) has been formulated which has constant rheology in the temperature range of 2-90 ℃, temperature tolerance of 160 ℃, seawater salinity tolerance of 5%, shale cuttings tolerance of 10%, and is environmentally friendly.展开更多
为改善页岩油气水平井钻进过程中因钻井液封堵性能差而引起的井壁失稳问题,首先,对川南龙马溪组页岩组成和井壁失稳的原因进行了分析;然后,以十六烷基三乙氧基硅烷、氨丙基三乙氧基硅烷和活性碳纳米管为原料,合成了油基钻井液用纳微米...为改善页岩油气水平井钻进过程中因钻井液封堵性能差而引起的井壁失稳问题,首先,对川南龙马溪组页岩组成和井壁失稳的原因进行了分析;然后,以十六烷基三乙氧基硅烷、氨丙基三乙氧基硅烷和活性碳纳米管为原料,合成了油基钻井液用纳微米封堵剂(NP-1),分别利用红外光谱分析、热重分析、透射电镜和表面润湿性测试分析其结构和物理化学特性,考察了其与油基钻井液的配伍性;最后,通过岩心突破压力、压力传递、三轴抗压强度等测试评价其封堵性能,分析了纳微米封堵剂的作用机理,并进行了现场应用。结果表明,川南龙马溪组页岩纳微米孔喉较发育,毛细自吸现象严重,使得液相不断侵入井壁,最终导致井壁失稳。NP-1的直径为30~50nm,长度处于微米级别,表面疏水亲油,在385.2℃以下的热稳定性良好。NP-1与油基钻井液具有良好的配伍性和稳定性。在常规油基钻井液中加入3%NP-1,在180℃下老化热滚16 h后的高温高压滤失量由2.8 mL降至1.8 m L。含有NP-1的油基钻井液能有效封堵岩心端面,从而提高岩心突破压力,阻止岩心压力传递,稳定岩心内部结构和抗压强度,实现维持井壁稳定的目的。现场应用结果表明,NP-1能有效改善邻井因钻井液封堵能力弱而引起的井漏、井壁失稳等技术难题,处理后的平均井径扩大率仅为5.61%。该纳微米封堵剂在油基钻井液中对页岩具有优异的封堵效果,为川南类似复杂页岩气井的高效钻探提供了借鉴。展开更多
Molecular crystals are complex systems exhibiting various crystal structures,and accurately modeling the crystal structures is essential for understanding their physical behaviors under high pressure.Here,we perform a...Molecular crystals are complex systems exhibiting various crystal structures,and accurately modeling the crystal structures is essential for understanding their physical behaviors under high pressure.Here,we perform an extensive structure search of ternary carbon-nitrogen-oxygen(CNO)compound under high pressure with the CALYPSO method and first principles calculations,and successfully identify three polymeric CNO compounds with Pbam,C2/m and I4m2symmetries under 100 GPa.More interestingly,these structures are also dynamically stable at ambient pressure,and are potential high energy density materials(HEDMs).The energy densities of Pbam,C2/m and I4m2 phases of CNO are about2.30 kJ/g,1.37 kJ/g and 2.70 kJ/g,respectively,with the decompositions of graphitic carbon and molecular carbon dioxide andα-N(molecular N_(2))at ambient pressure.The present results provide in-depth insights into the structural evolution and physical properties of CNO compounds under high pressures,which offer crucial insights for designs and syntheses of novel HEDMs.展开更多
Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excell...Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.展开更多
基金supported by Sichuan Science and Technology Program(No.2023YFS0170,2023NSFSC1931)supported by Medical Science and Technology Project of Sichuan Provincial Health Commission(No.21PJ009)+2 种基金supported by the National Natural Science Foundation of China(No.32222046,32371545,82103635)supported by the Technological innovation research and development project of Chengdu Science and Technology Bureau(2022-YF05-01589-SN)The 1⋅3⋅5 project of excellent development of discipline of West China Hospital of Sichuan University(No.ZYGC21022).
文摘Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor progression.The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.It can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells.Therefore,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor outcome.Thus,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.
文摘事故隐患分类能够直观反映企业安全生产管理的薄弱点,同时将直接决定企业优化安全管理工作的方向。油田安全生产过程中,隐患种类多,数据量大,单纯依赖人工方式分类及管理效率较低,且难以发掘数据中蕴含的潜在规律。基于油田安全生产的需求及事故隐患特征,提出了一种基于BERT-BiLSTM的分类模型,用于油田安全生产隐患文本的主题自动分类,通过基于Transformer的双向编码器表示(bidirectionalencoder representations from Transformer,BERT)模型提取输入文本的字符级特征,生成全局文本信息的向量表示,再通过双向长短时记忆网络(bi-directional long short-term memory,BiLSTM)模型对局部关键信息和上下文深层次特征进行特征提取,进而通过Softmax激活函数进行概率计算得到分类结果。通过与传统分类方法的比较表明,BERT-BiLSTM分类模型在加权平均准确率、加权平均召回率和加权平均F_(1)等指标方面均有所改善,模型与油田企业现有安全管理信息系统的有机融合将为进一步提升油田企业的事故隐患管理针对性,推动企业安全管理从事后被动反应向事前主动预防转变提供重要的技术支撑。
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11774100 and 11474106)
文摘Strain is a powerful tool to engineer the band structure of bilayer phosphorene.The band gap can be decreased by vertical tensile strain or in-plane compressive strain.At a critical strain,the gap is closed and the bilayer phosphorene is turn to be a semi-Dirac semimetal material.If the strain is stronger than the criterion,a band-inversion occurs and it re-happens when the strain is larger than another certain value.For the zigzag bilayer phosphorene ribbon,there are two edge band dispersions and each dispersion curve represents two degenerate edge bands.When the first band-inversion happens,one of the edge band dispersion disappears between the band-cross points while the other survives,and the latter will be eliminated between another pair of band-cross points of the second band-inversion.The optical absorption of bilayer phosphorene is highly polarized along armchair direction.When the strain is turn on,the optical absorption edge changes.The absorption rate for armchair polarized light is decreased by gap shrinking,while that for zigzag polarized light increases.The bandtouch and band-inversion respectively result in the sublinear and linear of absorption curve versus light frequency in low frequency limit.
基金Supported by the NSFC Innovative Research Group(51821092)NSFC Foundation(52004297)+1 种基金China Postdoctoral Science Foundation(BX20200384)China University of Petroleum(Beijing)Foundation(2462020XKBH00)。
文摘As the base oil of the current flat-rheology synthetic drilling fluid is high in cost and not renewable, the biodiesel-based flat-rheology drilling fluid with low-cost, environmental protection and renewable advantage was studied. Based on the optimization of raw materials, a cheap, environment-friendly biodiesel of soybean oil ethyl ester with good fluidity at low temperature was selected as the base oil. By selecting high oil-water ratio and introducing cationic surfactant into the auxiliary emulsifier, the thickening of biodiesel-based emulsion caused by hydrolysis and saponification after high-temperature aging was effectively eliminated. The organoclay prepared with cationic modifier of hexadecyl trimethyl ammonium chloride was used to improve the rheologic properties, stability and fluid loss of the drilling fluid while preventing low-temperature thickening. A flat-rheology modifier was synthesized with dimer fatty acid and cocoanut fatty acid diethanolamide, which could form strong network structure in the biodiesel-based drilling fluid to adjust effectively rheological properties of the drilling fluid. A biodiesel-based flat-rheology drilling fluid system with the density of 1.2 g/cm^(3) has been formulated which has constant rheology in the temperature range of 2-90 ℃, temperature tolerance of 160 ℃, seawater salinity tolerance of 5%, shale cuttings tolerance of 10%, and is environmentally friendly.
文摘为改善页岩油气水平井钻进过程中因钻井液封堵性能差而引起的井壁失稳问题,首先,对川南龙马溪组页岩组成和井壁失稳的原因进行了分析;然后,以十六烷基三乙氧基硅烷、氨丙基三乙氧基硅烷和活性碳纳米管为原料,合成了油基钻井液用纳微米封堵剂(NP-1),分别利用红外光谱分析、热重分析、透射电镜和表面润湿性测试分析其结构和物理化学特性,考察了其与油基钻井液的配伍性;最后,通过岩心突破压力、压力传递、三轴抗压强度等测试评价其封堵性能,分析了纳微米封堵剂的作用机理,并进行了现场应用。结果表明,川南龙马溪组页岩纳微米孔喉较发育,毛细自吸现象严重,使得液相不断侵入井壁,最终导致井壁失稳。NP-1的直径为30~50nm,长度处于微米级别,表面疏水亲油,在385.2℃以下的热稳定性良好。NP-1与油基钻井液具有良好的配伍性和稳定性。在常规油基钻井液中加入3%NP-1,在180℃下老化热滚16 h后的高温高压滤失量由2.8 mL降至1.8 m L。含有NP-1的油基钻井液能有效封堵岩心端面,从而提高岩心突破压力,阻止岩心压力传递,稳定岩心内部结构和抗压强度,实现维持井壁稳定的目的。现场应用结果表明,NP-1能有效改善邻井因钻井液封堵能力弱而引起的井漏、井壁失稳等技术难题,处理后的平均井径扩大率仅为5.61%。该纳微米封堵剂在油基钻井液中对页岩具有优异的封堵效果,为川南类似复杂页岩气井的高效钻探提供了借鉴。
基金the National Natural Science Foundation of China(Grant Nos.12174352 and 12111530103)the Fundamental Research Funds for the Central UniversitiesChina University of Geosciences(Wuhan)(Grant No.G1323523065)。
文摘Molecular crystals are complex systems exhibiting various crystal structures,and accurately modeling the crystal structures is essential for understanding their physical behaviors under high pressure.Here,we perform an extensive structure search of ternary carbon-nitrogen-oxygen(CNO)compound under high pressure with the CALYPSO method and first principles calculations,and successfully identify three polymeric CNO compounds with Pbam,C2/m and I4m2symmetries under 100 GPa.More interestingly,these structures are also dynamically stable at ambient pressure,and are potential high energy density materials(HEDMs).The energy densities of Pbam,C2/m and I4m2 phases of CNO are about2.30 kJ/g,1.37 kJ/g and 2.70 kJ/g,respectively,with the decompositions of graphitic carbon and molecular carbon dioxide andα-N(molecular N_(2))at ambient pressure.The present results provide in-depth insights into the structural evolution and physical properties of CNO compounds under high pressures,which offer crucial insights for designs and syntheses of novel HEDMs.
基金supported by the National Natural Science Foundation of China(Nos.32222046,82172630,82170844 and 82270613,China)the Sichuan Science and Technology Program(Nos.2022YFH0045 and 2022YFH0102,China)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21022,China).
文摘Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
