The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1...The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.展开更多
Objective:To explore the role of NLRP3 in mucus hypersecretion in asthmatic patients.Methods:From January 2020 to June 2022,90 patients with asthma and 60 healthy patients under the Department of Pulmonary and Critica...Objective:To explore the role of NLRP3 in mucus hypersecretion in asthmatic patients.Methods:From January 2020 to June 2022,90 patients with asthma and 60 healthy patients under the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Xi’an Medical University were selected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed.NLRP3 inflammasome and mucins MUC5AC and MUC5B levels in lung tissue and sputum were detected.Results:Compared to the healthy control group,the asthma group had significantly higher sputum MUC5A(20.12±5.07 versus 36.21±6.13)and NLRP3(72.31±15.13 versus 119.21±31.21)levels(P<0.05)but lower MUC5B levels(1.35±0.12 versus 0.53±0.11,P<0.05).Immunohistochemistry showed that NLRP3,MUC5AC,and MUC5B expressions were consistent with the sputum results.Conclusion:NLRP3 and MUC5AC levels are significantly increased in asthmatic patients,whereas MUC5B levels are reduced in these patients.They can be used as targets for the diagnosis and treatment of asthma.展开更多
The late Paleozoic evolution of the Wulijishanhen(WSH)-Shangdan(SD) area near to the Chaganchulu Ophiolite belt is reinterpreted. Analysis of the upper Carboniferous to lower Permian sedimentary sequence, biological a...The late Paleozoic evolution of the Wulijishanhen(WSH)-Shangdan(SD) area near to the Chaganchulu Ophiolite belt is reinterpreted. Analysis of the upper Carboniferous to lower Permian sedimentary sequence, biological associations, detrital materials, sandstone geochemistry and volcanic rocks indicates that the SD area was an epicontinental sea and rift during the late Paleozoic rather than a large-scale ocean undergoing spreading and closure. This study reveals that the actual evolution of the study area is from the late Carboniferous to the early Permian. The fusulinids Triticites sp. and Pseudoschwagerina sp.in the limestones demonstrate that the Amushan Formation develops during the late Carboniferous to the early Permian. The limestones at the base of the SD section indicate that it is a stable carbonate platform environment, the volcanic rocks in the middle of the sequence support a rift tectonic background, and the overlying conglomerates and sandstones are characteristic of an epicontinental sea or marine molasse setting. The rift volcanism made the differences in the fossil content of the SD and WSH sections and led to two sections expose different levels within the Amushan Formation and different process of tectonic evolution. Moreover, the geochemical characteristics and detrital materials of the sandstones show that the provenance and formation of the sandstones were related to the setting of active continental margin. The quartz-feldspar-lithic fragments distribution diagram indicates that the material source for the sandstones was a recycled orogenic belt. Thus, the source area of the sandstones may have been an active continental margin before the late Carboniferouseearly Permian. The characteristics of the regional tectonic evolution of the area indicate that the region may form a small part of the Gobie Tianshan rift of southern Mongolia.展开更多
The future of enterprises mainly depends on product research and development. For the modern enterprises, high performance project team is the most important means of R ＆ D projects. According to the interviews and s...The future of enterprises mainly depends on product research and development. For the modern enterprises, high performance project team is the most important means of R ＆ D projects. According to the interviews and survey found of a plurality of enterprise project R ＆ D team. the internal high performance team of modern business is good or bad, its key lies in whether the team managers for the team creation and management is in place, this is the most difficult place for the high performance team management system, especially the team leadership. Based on this, this paper discusses on the creation and management of high performance modern enterprise team, aiming to provide valuable reference for the enterprise team management.展开更多
Knowledge of the present-day in-situ stress distribution is greatly import-ant for better understanding of conventional and unconventional hydro-carbon reservoirs in many aspects,e.g,reservoir management,wellbore stab...Knowledge of the present-day in-situ stress distribution is greatly import-ant for better understanding of conventional and unconventional hydro-carbon reservoirs in many aspects,e.g,reservoir management,wellbore stability asssment,etc.In tectonically stable regions,the present-day in-situ stress field in terms of stress distribution is 1argely controlled by lithological changes,which can be predicted through|a numerical simulation method incorporating specific mechanical properties of the subsurface reservoir.In this study,a workflow was presented to predict the present-day in-situ stress field based on the finite element method(FEM).Sequentially,it consists of:i)building a three-dimensional(3D)geometric framework,i)creating a 3D petrophysical parameter field,11)integrating the geometric framework with petrophysical parameters,iv)setting up a 3D heterogeneous geomechanical model,and finally,v)calculating the present-day in-situ stress distribution and calibrating the prediction with measured stress data,e.g.,results from the extended leak-off tests(XLOTs).The approach was sucessfully applied to the Block W in Ordos Basin of central China.The results indicated that the workflow and models presented in this study could be used as an effective tool to provide insights into stress perturbations in subsurface reservoirs and geological references for subsequent analysis.展开更多
Invasions by Spartina species pose serious threats to global coastal ecosystems.Although many studies have examined the effectiveness and ecological impacts of invasive Spartina management,no comprehensive global synt...Invasions by Spartina species pose serious threats to global coastal ecosystems.Although many studies have examined the effectiveness and ecological impacts of invasive Spartina management,no comprehensive global synthesis has been conducted to assess the effects of management on Spartina per se and on wider non-targets.Here,we conducted a global meta-analysis of 3,459 observations from 102 studies to quantify the effects of different management interventions(physical,chemical,biological,and integrated control)on Spartina per se and native biodiversity and environments.We found that physical measures quickly suppressed Spartina but that their effectiveness declined over time.By contrast,chemical measures decreased the abundance and growth of Spartina to a lesser degree in the early stage,but the effectiveness increased over time.Different management measures did not significantly decrease the diversity of native biota on the whole,but native-plant diversity significantly decreased with time after physical control.Different management measures did not affect abiotic factors differently.These results support the use of chemical measures to control invasive Spartina,although their effectiveness would depend on the time since the management intervention.Addressing the problem of Spartina regrowth following physical control requires improved techniques.We hold that initial states of invaders and subsequent environmental changes after management interventions should be weighed in evaluating control efficacy.展开更多
A simple method using a water soluble lignin quaternary ammonium salt (LQAS) and TiO2 has been developed for the preparation of lignin/TiO2 nanocomposites in an aqueous medium under mild conditions. The LQAS/TiO2 nano...A simple method using a water soluble lignin quaternary ammonium salt (LQAS) and TiO2 has been developed for the preparation of lignin/TiO2 nanocomposites in an aqueous medium under mild conditions. The LQAS/TiO2 nanocomposites contain well-dispersed small particles with excellent ultraviolet (UV) shielding abilities and good compatibilities with waterborne polyurethane (WPU). When the LQAS/TiO2 nanocomposites were blended with WPU, the UV absorbance and the tensile ductility of the WPU increased significantly. The composite WPU hybrid film containing 6 wt-% LQAS/TiO2 nanocomposite had the highest visible light transmittance and had excellent ultraviolet aging properties. After 192 h of UV light irradiation, the tensile strength of the composite film was above 8 MPa and the elongation at break was 800%. This work highlights new possibilities for the utilization of alkali lignin.展开更多
The apoptosis inducing effects on tumor cell lines MGC803, BEL7402 and HL60 by Fas ligand and anti-human DR5 monoclonal antibodies (anti-DR5 mAb) and the underlying mechanism was studied. Fas/DR5 mRNA was detected by ...The apoptosis inducing effects on tumor cell lines MGC803, BEL7402 and HL60 by Fas ligand and anti-human DR5 monoclonal antibodies (anti-DR5 mAb) and the underlying mechanism was studied. Fas/DR5 mRNA was detected by RT-PCR. Cytotoxicity exerted by FasL/anti-DR5 mAb on tumor cell lines was measured by MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. Flow cytometry was employed to analyze the mode of cell death. The mRNA expression of DR5 in MGC803 and BEL7402 cells after giving anti-DR5 mAb was up-regulated compared with control group, while it was down-regulated in HL60 cells in the same condition. The mRNA expression of Fas in HL60 was higher after giving FasL compared with control group, while it was lower in MGC803 and BEL7402. MGC803 and BEL7402 were sensitive to anti-DR5 mAb but partially to FasL, and HL60 was sensitive to FasL but less sensitive to anti-DR5 mAb. Apoptosis induced by Fas ligand and anti-DR5 mAb vary among tumor cell lines. The underlying mechanism may be relevant to Fas/DR5 mRNA expression, which was presented as the release of caspase-8 and Bcl-2.展开更多
hSHIP,a human SH2-containing inositol-5-phosphatase,acts as a negative regulator of proliferation and survival in hematopoietic cells.Therefore,hSHIP may play a crucial role in suppression of cervical cancer HeLa cell...hSHIP,a human SH2-containing inositol-5-phosphatase,acts as a negative regulator of proliferation and survival in hematopoietic cells.Therefore,hSHIP may play a crucial role in suppression of cervical cancer HeLa cells.In this study,pcDNA3.1-hSHIP-GFP plasmid was constructed and transfected into HeLa cells with Lipofectamine2000,stably transfected HeLa cells were established and their responses were investigated by Flow cytometry,MTT,tumorigenicity in nude mice,RT-PCR and ELISA assays.The results showed that the expression of hSHIP significantly induced S-phase arrest,cell growth inhibition,and down-regulation of Akt1/2 mRNA and p-Akt in HeLa cells.Our study supports an important role for hSHIP in suppression of cervical cancer HeLa cells,which may prove to be a novel therapeutic option for non-hematopoietic cancers.展开更多
Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation ar...Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc(IVD)degeneration.Herein,we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid(HA-CHO)and poly(amidoamine)PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment,where the formation of dynamic Schiff base bonds in the system(siSTING@HPgel)was able to overcome the shortcomings such as low cellular uptake,short half-life,and rapid degradation of siRNA-based strategy.PAMAM not only formed complexes with siRNA to promote siRNA transfection,but also served as dynamic crosslinker to construct hydrogel,and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells.Finally,the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model,revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.展开更多
Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low effica...Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones.Here,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD.By simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T cells.The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis.Together,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance.展开更多
Pore pressure is an important parameter in coalbed methane(CBM)exploration and development;however,the distribution pattern and mechanism for pore pressure differences in the Upper Permian CBM reservoirs are poorly un...Pore pressure is an important parameter in coalbed methane(CBM)exploration and development;however,the distribution pattern and mechanism for pore pressure differences in the Upper Permian CBM reservoirs are poorly understood in the western Guizhou region of South China.In this study,lateral and vertical variations and mechanisms for pore pressure differences are analyzed based on 126 injection-falloff and in-situ stress well test data measured in Permian coal reservoirs.Generally,based on the pore pressure gradient and coefficient in coal reservoirs of the western Guizhou region,five zones can be delineated laterally:the mining areas of Zhina,northem Liupanshui,northern Guizhou,northwestern Guizhou and southern Liupanshui.Vertically,there are two main typical patterns:i)the pore pressure gradient(or coefficient)is nearly unchanged in different coal reservoirs,and ii)the pore pressure gradient(or coefficient)has cyclic variations in a borehole profile with multiple coal seams,which suggests the existence of a"superimposed CBM system".The mechanism analysis indicates that coal permeability,thermal evolution stage and hydrocarbon generation contribute little to pore pressure differences in coal reservoirs in the western Guizhou region.The present-day in-situ stress field,basement structure and tectonic activity may be the dominant factors affecting lateral pore pressure differences.The sealing capacity of caprocks and the present-day in-situ stress field are significant para-meters causing vertical pore pressure differences in coal reservoirs.These results are expected to provide new geological references for CBM exploration and develop-ment in the western Guizhou region.展开更多
基金supported by the Natural Science Foundation of Xiamen City(3502Z20227307)the National Natural Science Foundation of China(81472458,82372809)the Special Fund for Public Welfare Research Institutes of Fujian Province(2023R1001001,2023R1001003,2023R1035).
文摘The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.
基金This work was supported by Xi’an Science and Technology Plan Project(22YXYJ0136).
文摘Objective:To explore the role of NLRP3 in mucus hypersecretion in asthmatic patients.Methods:From January 2020 to June 2022,90 patients with asthma and 60 healthy patients under the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Xi’an Medical University were selected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed.NLRP3 inflammasome and mucins MUC5AC and MUC5B levels in lung tissue and sputum were detected.Results:Compared to the healthy control group,the asthma group had significantly higher sputum MUC5A(20.12±5.07 versus 36.21±6.13)and NLRP3(72.31±15.13 versus 119.21±31.21)levels(P<0.05)but lower MUC5B levels(1.35±0.12 versus 0.53±0.11,P<0.05).Immunohistochemistry showed that NLRP3,MUC5AC,and MUC5B expressions were consistent with the sputum results.Conclusion:NLRP3 and MUC5AC levels are significantly increased in asthmatic patients,whereas MUC5B levels are reduced in these patients.They can be used as targets for the diagnosis and treatment of asthma.
基金financially supported by the China Geological Survey (Grant No. [2010] 01-09-11)
文摘The late Paleozoic evolution of the Wulijishanhen(WSH)-Shangdan(SD) area near to the Chaganchulu Ophiolite belt is reinterpreted. Analysis of the upper Carboniferous to lower Permian sedimentary sequence, biological associations, detrital materials, sandstone geochemistry and volcanic rocks indicates that the SD area was an epicontinental sea and rift during the late Paleozoic rather than a large-scale ocean undergoing spreading and closure. This study reveals that the actual evolution of the study area is from the late Carboniferous to the early Permian. The fusulinids Triticites sp. and Pseudoschwagerina sp.in the limestones demonstrate that the Amushan Formation develops during the late Carboniferous to the early Permian. The limestones at the base of the SD section indicate that it is a stable carbonate platform environment, the volcanic rocks in the middle of the sequence support a rift tectonic background, and the overlying conglomerates and sandstones are characteristic of an epicontinental sea or marine molasse setting. The rift volcanism made the differences in the fossil content of the SD and WSH sections and led to two sections expose different levels within the Amushan Formation and different process of tectonic evolution. Moreover, the geochemical characteristics and detrital materials of the sandstones show that the provenance and formation of the sandstones were related to the setting of active continental margin. The quartz-feldspar-lithic fragments distribution diagram indicates that the material source for the sandstones was a recycled orogenic belt. Thus, the source area of the sandstones may have been an active continental margin before the late Carboniferouseearly Permian. The characteristics of the regional tectonic evolution of the area indicate that the region may form a small part of the Gobie Tianshan rift of southern Mongolia.
文摘The future of enterprises mainly depends on product research and development. For the modern enterprises, high performance project team is the most important means of R ＆ D projects. According to the interviews and survey found of a plurality of enterprise project R ＆ D team. the internal high performance team of modern business is good or bad, its key lies in whether the team managers for the team creation and management is in place, this is the most difficult place for the high performance team management system, especially the team leadership. Based on this, this paper discusses on the creation and management of high performance modern enterprise team, aiming to provide valuable reference for the enterprise team management.
文摘Knowledge of the present-day in-situ stress distribution is greatly import-ant for better understanding of conventional and unconventional hydro-carbon reservoirs in many aspects,e.g,reservoir management,wellbore stability asssment,etc.In tectonically stable regions,the present-day in-situ stress field in terms of stress distribution is 1argely controlled by lithological changes,which can be predicted through|a numerical simulation method incorporating specific mechanical properties of the subsurface reservoir.In this study,a workflow was presented to predict the present-day in-situ stress field based on the finite element method(FEM).Sequentially,it consists of:i)building a three-dimensional(3D)geometric framework,i)creating a 3D petrophysical parameter field,11)integrating the geometric framework with petrophysical parameters,iv)setting up a 3D heterogeneous geomechanical model,and finally,v)calculating the present-day in-situ stress distribution and calibrating the prediction with measured stress data,e.g.,results from the extended leak-off tests(XLOTs).The approach was sucessfully applied to the Block W in Ordos Basin of central China.The results indicated that the workflow and models presented in this study could be used as an effective tool to provide insights into stress perturbations in subsurface reservoirs and geological references for subsequent analysis.
基金supported by the National Key Research and Development Program of China(No.2022YFC2601100)the National Natural Science Foundation of China(Nos.32030067,32171661)+1 种基金the Arcadia,MAVA and the David and Claudia Harding Foundation,the Special Project on National Science and Technology Basic Resources Investigation of China(No.2021FY100704)the Yellow Sea Wetland Research Institute(No.20210111).
文摘Invasions by Spartina species pose serious threats to global coastal ecosystems.Although many studies have examined the effectiveness and ecological impacts of invasive Spartina management,no comprehensive global synthesis has been conducted to assess the effects of management on Spartina per se and on wider non-targets.Here,we conducted a global meta-analysis of 3,459 observations from 102 studies to quantify the effects of different management interventions(physical,chemical,biological,and integrated control)on Spartina per se and native biodiversity and environments.We found that physical measures quickly suppressed Spartina but that their effectiveness declined over time.By contrast,chemical measures decreased the abundance and growth of Spartina to a lesser degree in the early stage,but the effectiveness increased over time.Different management measures did not significantly decrease the diversity of native biota on the whole,but native-plant diversity significantly decreased with time after physical control.Different management measures did not affect abiotic factors differently.These results support the use of chemical measures to control invasive Spartina,although their effectiveness would depend on the time since the management intervention.Addressing the problem of Spartina regrowth following physical control requires improved techniques.We hold that initial states of invaders and subsequent environmental changes after management interventions should be weighed in evaluating control efficacy.
基金the National Natural Science Foundation of China (Grant Nos. 21436004 and 21706082)the Science and Technology Program of Guangzhou (201707020025)+1 种基金the Fundamental Research Funds for the Central Universities (D2174110)Guangdong Province Science Foundation for Cultivating National Engineering Research Center for Efficient Utilization of Plant Fibers (2017B090903003) for the financial support.
文摘A simple method using a water soluble lignin quaternary ammonium salt (LQAS) and TiO2 has been developed for the preparation of lignin/TiO2 nanocomposites in an aqueous medium under mild conditions. The LQAS/TiO2 nanocomposites contain well-dispersed small particles with excellent ultraviolet (UV) shielding abilities and good compatibilities with waterborne polyurethane (WPU). When the LQAS/TiO2 nanocomposites were blended with WPU, the UV absorbance and the tensile ductility of the WPU increased significantly. The composite WPU hybrid film containing 6 wt-% LQAS/TiO2 nanocomposite had the highest visible light transmittance and had excellent ultraviolet aging properties. After 192 h of UV light irradiation, the tensile strength of the composite film was above 8 MPa and the elongation at break was 800%. This work highlights new possibilities for the utilization of alkali lignin.
文摘The apoptosis inducing effects on tumor cell lines MGC803, BEL7402 and HL60 by Fas ligand and anti-human DR5 monoclonal antibodies (anti-DR5 mAb) and the underlying mechanism was studied. Fas/DR5 mRNA was detected by RT-PCR. Cytotoxicity exerted by FasL/anti-DR5 mAb on tumor cell lines was measured by MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. Flow cytometry was employed to analyze the mode of cell death. The mRNA expression of DR5 in MGC803 and BEL7402 cells after giving anti-DR5 mAb was up-regulated compared with control group, while it was down-regulated in HL60 cells in the same condition. The mRNA expression of Fas in HL60 was higher after giving FasL compared with control group, while it was lower in MGC803 and BEL7402. MGC803 and BEL7402 were sensitive to anti-DR5 mAb but partially to FasL, and HL60 was sensitive to FasL but less sensitive to anti-DR5 mAb. Apoptosis induced by Fas ligand and anti-DR5 mAb vary among tumor cell lines. The underlying mechanism may be relevant to Fas/DR5 mRNA expression, which was presented as the release of caspase-8 and Bcl-2.
基金supported by 985 Research Foundation of Xiamen UniversityResearch Foundation of Cancer Research Center,Xiamen University
文摘hSHIP,a human SH2-containing inositol-5-phosphatase,acts as a negative regulator of proliferation and survival in hematopoietic cells.Therefore,hSHIP may play a crucial role in suppression of cervical cancer HeLa cells.In this study,pcDNA3.1-hSHIP-GFP plasmid was constructed and transfected into HeLa cells with Lipofectamine2000,stably transfected HeLa cells were established and their responses were investigated by Flow cytometry,MTT,tumorigenicity in nude mice,RT-PCR and ELISA assays.The results showed that the expression of hSHIP significantly induced S-phase arrest,cell growth inhibition,and down-regulation of Akt1/2 mRNA and p-Akt in HeLa cells.Our study supports an important role for hSHIP in suppression of cervical cancer HeLa cells,which may prove to be a novel therapeutic option for non-hematopoietic cancers.
基金The study was sponsored by National Natural Science Foundation of China(81672150,51903050)Zhejiang medical and health science and technology project(2018KY117,2019ZD041)+1 种基金Natural Science Foundation of Zhejiang Province of China(LQ20H160053)New talent in medical field of Zhejiang Province,and the fundamental research funds for the central universities(2019QNA7027).
文摘Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc(IVD)degeneration.Herein,we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid(HA-CHO)and poly(amidoamine)PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment,where the formation of dynamic Schiff base bonds in the system(siSTING@HPgel)was able to overcome the shortcomings such as low cellular uptake,short half-life,and rapid degradation of siRNA-based strategy.PAMAM not only formed complexes with siRNA to promote siRNA transfection,but also served as dynamic crosslinker to construct hydrogel,and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells.Finally,the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model,revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.
基金supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01,China)ZJ Lab,Shanghai Natural Science Foundation(Grant No.18ZR1405700,China)+3 种基金National Natural Science Foundation of China(Fund Nos.81773283 and 81901697)Shanghai Sailing Program(Grant No.18YF1403000,China)Shanghai Chest Hospital Project of Collaborative Innovation(Grant No.YJXT20190203,China)the Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure(SKL201908SIC,China)。
文摘Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones.Here,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD.By simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T cells.The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis.Together,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance.
基金supported by Natural Science Foundation of Jiangsu Province,China(No.BK20201349)National Natural Science Foundation of China(Grant Nos.41702130 and 41971335)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Pore pressure is an important parameter in coalbed methane(CBM)exploration and development;however,the distribution pattern and mechanism for pore pressure differences in the Upper Permian CBM reservoirs are poorly understood in the western Guizhou region of South China.In this study,lateral and vertical variations and mechanisms for pore pressure differences are analyzed based on 126 injection-falloff and in-situ stress well test data measured in Permian coal reservoirs.Generally,based on the pore pressure gradient and coefficient in coal reservoirs of the western Guizhou region,five zones can be delineated laterally:the mining areas of Zhina,northem Liupanshui,northern Guizhou,northwestern Guizhou and southern Liupanshui.Vertically,there are two main typical patterns:i)the pore pressure gradient(or coefficient)is nearly unchanged in different coal reservoirs,and ii)the pore pressure gradient(or coefficient)has cyclic variations in a borehole profile with multiple coal seams,which suggests the existence of a"superimposed CBM system".The mechanism analysis indicates that coal permeability,thermal evolution stage and hydrocarbon generation contribute little to pore pressure differences in coal reservoirs in the western Guizhou region.The present-day in-situ stress field,basement structure and tectonic activity may be the dominant factors affecting lateral pore pressure differences.The sealing capacity of caprocks and the present-day in-situ stress field are significant para-meters causing vertical pore pressure differences in coal reservoirs.These results are expected to provide new geological references for CBM exploration and develop-ment in the western Guizhou region.
