<strong>Background:</strong> Prone positioning is nowadays considered as one of the most effective strategies for patients with severe acute respiratory distress syndrome (ARDS). Prone position ventilation...<strong>Background:</strong> Prone positioning is nowadays considered as one of the most effective strategies for patients with severe acute respiratory distress syndrome (ARDS). Prone position ventilation can lead to some severe complications. Effectively implement prone ventilation and reduce the incidence of complications become an important problem for clinical medical staff. <strong>Aims: </strong>To investigate whether the Sandwich rolling over method was convenient for clinical implementation and can reduce complications. <strong>Design:</strong> This is a single-center, retrospective, observational study.<strong> Results:</strong> The mean pronation cycles per patient were 6.11 <span style="white-space:nowrap;">±</span> 4.40. The mean time spent in prone position for each cycle was 10.05 <span style="white-space:nowrap;">±</span> 4.42 hours. Two patients developed a pressure sore and the positions were cheek, auricle and chest. The mean time it took from preparation to cover the patient with the quilt was 10.56 <span style="white-space:nowrap;">±</span> 4.35 minutes. Conclusions: This retrospective study has shown that under the close cooperation and supervision of the team, the implementation efficiency of prone position ventilation can be improved and the occurrence of complications can be reduced.展开更多
The drawbacks of the traditional multi-hop structure of wireless sensor networks(WSNS)are susceptible to reflection,scattering and diffraction,serious attenuation of signal intensity and phase deviation due to various...The drawbacks of the traditional multi-hop structure of wireless sensor networks(WSNS)are susceptible to reflection,scattering and diffraction,serious attenuation of signal intensity and phase deviation due to various obstacles in cultivated land environment and mountains.In this paper,the wireless signal intensity is measured and curve fitting is done respectively in both open environment and obstacle-environment with both sending and receiving height of 0 m,1 m,and 2 m.It is found out that packet loss probability is too high when an obstacle exists.In such a case,unmanned aerial vehicle(UAV)is introduced to activate terrestrial nodes and operation mechanism of distributed storage.Experimental results show that both ground-to-air barrier-free communication and communication with obstacles can greatly reduce the energy consumption of each node and packet loss probability,thus greatly improving the reliability of UAV-WSN system.展开更多
Based on the two-dimensional relation table,this paper studies the missing values in the sample data of land price of Shunde District of Foshan City.GeoDa software was used to eliminate the insignificant factors by st...Based on the two-dimensional relation table,this paper studies the missing values in the sample data of land price of Shunde District of Foshan City.GeoDa software was used to eliminate the insignificant factors by stepwise regression analysis;NORM software was adopted to construct the multiple imputation models;EM algorithm and the augmentation algorithm were applied to fit multiple linear regression equations to construct five different filling datasets.Statistical analysis is performed on the imputation data set in order to calculate the mean and variance of each data set,and the weight is determined according to the differences.Finally,comprehensive integration is implemented to achieve the imputation expression of missing values.The results showed that in the three missing cases where the PRICE variable was missing and the deletion rate was 5%,the PRICE variable was missing and the deletion rate was 10%,and the PRICE variable and the CBD variable were both missing.The new method compared to the traditional multiple filling methods of true value closer ratio is 75%to 25%,62.5%to 37.5%,100%to 0%.Therefore,the new method is obviously better than the traditional multiple imputation methods,and the missing value data estimated by the new method bears certain reference value.展开更多
Calculation of the groundwater recoverable resource is the main part of groundwater resource evaluation. The three-dimensional groundwater flow model in Linfen Basin was established by GMS software. Then the numerical...Calculation of the groundwater recoverable resource is the main part of groundwater resource evaluation. The three-dimensional groundwater flow model in Linfen Basin was established by GMS software. Then the numerical model was calibrated by observed groundwater level from February to December in 2 000. Based on the calibrated model, the groundwater recoverable resource is calculated. The simulation result shows that under the given value of the groundwater recoverable resource, the groundwater level would decrease significantly in the first 1 000 days, while the water level would drop slowly in 1 000 to 2 000 days, and the water level change tend to be stable after 2000 days.展开更多
Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cance...Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases.Herein,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse.In addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT sensitization.RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune system.Thus,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor microenvironment.Furthermore,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative recurrence.Overall,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.展开更多
Norovirus is an infectious disease that can cause non-bacterial gastroenteritis,which has a low infectious dose,rapid onset,and strong transmission ability;therefore,rapid and sensitive detection is essential to reduc...Norovirus is an infectious disease that can cause non-bacterial gastroenteritis,which has a low infectious dose,rapid onset,and strong transmission ability;therefore,rapid and sensitive detection is essential to reduce the transmission of gastroenteritis.In the study,a norovirus GII loop-mediated isothermal amplification assay was developed and prepared into freeze-drying microspheres,and a closed-cassette-based,integrated,reagent-ambient storage,on-site instant detection platform for norovirus GII was constructed using a commercial,fully automated nucleic acid analyzer with integrated magnetic bearing based nuclear acid extraction and nucleic acid detection,with a sensitivity of 10 copies/μL,with no cross-reactivity with other 5 viruses.For 28 simulated samples,the integrated assay platform was consistent with the experimental results of reverse transcription-quantitative polymerase chain reaction(RT-qPCR)assays after conventional laboratory nucleic acid extraction.The entire process can be finished in about 1 h,which is ideal for immediate rapid detection.展开更多
Single-molecule junctions,integrating individual molecules as active components between electrodes,serve as fundamental building blocks for advanced electronic and sensing technologies.The application of ionic liquids...Single-molecule junctions,integrating individual molecules as active components between electrodes,serve as fundamental building blocks for advanced electronic and sensing technologies.The application of ionic liquids in single-molecule junctions represents a cutting-edge and rapidly evolving field of research at the intersection of nanoscience,materials chemistry,and electronics.This review explores recent advances where ionic liquids function as electrolytes,dielectric layers,and structural elements within single-molecule junctions,reshaping charge transport,redox reactions,and molecular behaviors in these nanoscale systems.We comprehensively dissect fundamental concepts,techniques,and modulation mechanisms,elucidating the roles of ionic liquids as gates,electrochemical controllers,and interface components in singlemolecule junctions.Encompassing applications from functional device construction to unraveling intricate chemical reactions,this review maps the diverse applications of ionic liquids in single-molecule junctions.Moreover,we propose critical future research topics in this field,including catalysis involving ionic liquids at the single-molecule level,functionalizing single-molecule devices using ionic liquids,and probing the structure and interactions of ionic liquids.These endeavors aim to drive technological breakthroughs in nanotechnology,energy,and quantum research.展开更多
Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of thi...Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently.Here,we showed that IMMH002,a novel orally active S1 P1 modulator,desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus.Using different psoriasis animal models,we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PAS I score and pathological injure evaluation.Mechanistically,IMMH002 regulated CD3+T lymphocytes re-distribution by inducing lymphocytes’homing,thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus.Our results suggest that the novel SIP1 agonist,IMMH002,exert extraordinary capacity to rapidly modulate T lymphocytes distribution,representing a promising drug candidate for psoriasis treatment.展开更多
Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective inter...Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.展开更多
Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the...Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis.Results:Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity,including increasing production of nitric oxide(NO),tumor necrosis factor a(TNFa)and upregulating mRNA levels of inducible NO synthase(iNOS)and TNFa.Furthermore,modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B(NF-κB).Conclusion:The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.展开更多
Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways,it is still unclear how certain drugs influence these P53 signaling netw orks.Here,we used a comprehensive singlecell multio...Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways,it is still unclear how certain drugs influence these P53 signaling netw orks.Here,we used a comprehensive singlecell multiomics view of the effects of ginsenosides on cancer cells.Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely as sociated with P53 protein.A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins,and proteomemetabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism,amino acid metabolism and"Warburg effect".The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides.Furthermore,by applying affinity mass spectrometry(MS)screening and surface plasmon resonance fragment library screening,we confirmed that 20(S)-protopanaxatriol directly targeted adj acent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions,which further induced a series of omics changes.展开更多
The interleukin-1β-mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways are involved in the pathogenesis of rheumatoid arthritis. Ebosin, a novel exopolysaccharide (EPS), exhibits anti-inflammato...The interleukin-1β-mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways are involved in the pathogenesis of rheumatoid arthritis. Ebosin, a novel exopolysaccharide (EPS), exhibits anti-inflammatory activity in rat collagen-induced arthritis by suppressing the production of tumor necrosis factor-s, interleukin-6 and interleukin-1β. The aim of the present study was to assess the effects of ebosin on NF-KB and MAPK signaling pathways mediated through interleukin-1β. in rat fibroblast-like synoviocytes (FLSs). Western blotting showed decreased production of phosphorylated p38, JNK1, JNK2, IKKa, IKKa, and IκB in the cytoplasm and NF-κB in the nucleus upon ebosin treatment. The DNA-binding activity of NF-KB in the cell nucleus was also inhibited by ebosin treatment, as demonstrated using an electrophoresis mobility gel shift assay. Analysis of the results of the immunofluorescence assay also showed a reduced amount of NF-KB in the nucleus of cells affected by ebosin. These results provided evidence for the effects of ebosin on both interleukin-1β-mediated MAPK and NF-κB signaling pathways in rat FLSs. In addition, enzyme-linked immunosorbent assay demonstrated that ebosin reduces the levels of matrix metalloproteinases MMP-1 and MMP-3 and the chemokines, interleukin-8 and RANTES. Thus, the results of the present study provide further evidence for understanding the medicinal activity of ebosin at a molecular level, therefore nominating this EPS as a potential therapeutic candidate for the treatment of rheumatic arthritis.展开更多
文摘<strong>Background:</strong> Prone positioning is nowadays considered as one of the most effective strategies for patients with severe acute respiratory distress syndrome (ARDS). Prone position ventilation can lead to some severe complications. Effectively implement prone ventilation and reduce the incidence of complications become an important problem for clinical medical staff. <strong>Aims: </strong>To investigate whether the Sandwich rolling over method was convenient for clinical implementation and can reduce complications. <strong>Design:</strong> This is a single-center, retrospective, observational study.<strong> Results:</strong> The mean pronation cycles per patient were 6.11 <span style="white-space:nowrap;">±</span> 4.40. The mean time spent in prone position for each cycle was 10.05 <span style="white-space:nowrap;">±</span> 4.42 hours. Two patients developed a pressure sore and the positions were cheek, auricle and chest. The mean time it took from preparation to cover the patient with the quilt was 10.56 <span style="white-space:nowrap;">±</span> 4.35 minutes. Conclusions: This retrospective study has shown that under the close cooperation and supervision of the team, the implementation efficiency of prone position ventilation can be improved and the occurrence of complications can be reduced.
文摘The drawbacks of the traditional multi-hop structure of wireless sensor networks(WSNS)are susceptible to reflection,scattering and diffraction,serious attenuation of signal intensity and phase deviation due to various obstacles in cultivated land environment and mountains.In this paper,the wireless signal intensity is measured and curve fitting is done respectively in both open environment and obstacle-environment with both sending and receiving height of 0 m,1 m,and 2 m.It is found out that packet loss probability is too high when an obstacle exists.In such a case,unmanned aerial vehicle(UAV)is introduced to activate terrestrial nodes and operation mechanism of distributed storage.Experimental results show that both ground-to-air barrier-free communication and communication with obstacles can greatly reduce the energy consumption of each node and packet loss probability,thus greatly improving the reliability of UAV-WSN system.
基金This research was financially supported by FDCT NO.005/2018/A1also supported by Guangdong Provincial Innovation and Entrepreneurship Training Program Project No.201713719017College Students Innovation Training Program held by Guangdong university of Science and Technology Nos.1711034,1711080,and No.1711088.
文摘Based on the two-dimensional relation table,this paper studies the missing values in the sample data of land price of Shunde District of Foshan City.GeoDa software was used to eliminate the insignificant factors by stepwise regression analysis;NORM software was adopted to construct the multiple imputation models;EM algorithm and the augmentation algorithm were applied to fit multiple linear regression equations to construct five different filling datasets.Statistical analysis is performed on the imputation data set in order to calculate the mean and variance of each data set,and the weight is determined according to the differences.Finally,comprehensive integration is implemented to achieve the imputation expression of missing values.The results showed that in the three missing cases where the PRICE variable was missing and the deletion rate was 5%,the PRICE variable was missing and the deletion rate was 10%,and the PRICE variable and the CBD variable were both missing.The new method compared to the traditional multiple filling methods of true value closer ratio is 75%to 25%,62.5%to 37.5%,100%to 0%.Therefore,the new method is obviously better than the traditional multiple imputation methods,and the missing value data estimated by the new method bears certain reference value.
基金National Basic Research Program of China (No. G1999043606)
文摘Calculation of the groundwater recoverable resource is the main part of groundwater resource evaluation. The three-dimensional groundwater flow model in Linfen Basin was established by GMS software. Then the numerical model was calibrated by observed groundwater level from February to December in 2 000. Based on the calibrated model, the groundwater recoverable resource is calculated. The simulation result shows that under the given value of the groundwater recoverable resource, the groundwater level would decrease significantly in the first 1 000 days, while the water level would drop slowly in 1 000 to 2 000 days, and the water level change tend to be stable after 2000 days.
基金supported by the National Natural Science Foundation of China(82172094)Funds of Sichuan Province for Distinguished Young Scholar(2021JDJQ0037,China)。
文摘Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases.Herein,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse.In addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT sensitization.RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune system.Thus,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor microenvironment.Furthermore,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative recurrence.Overall,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
基金funded by the Science and Technology Development Fund,Macao SAR(Nos.0065/2020/A2,SKLQRCM(MUST)-2020-2022)Shenzhen-Hong Kong-Macao Science and Technology Project(Grade c)(No.SGDX20210823104201010).
文摘Norovirus is an infectious disease that can cause non-bacterial gastroenteritis,which has a low infectious dose,rapid onset,and strong transmission ability;therefore,rapid and sensitive detection is essential to reduce the transmission of gastroenteritis.In the study,a norovirus GII loop-mediated isothermal amplification assay was developed and prepared into freeze-drying microspheres,and a closed-cassette-based,integrated,reagent-ambient storage,on-site instant detection platform for norovirus GII was constructed using a commercial,fully automated nucleic acid analyzer with integrated magnetic bearing based nuclear acid extraction and nucleic acid detection,with a sensitivity of 10 copies/μL,with no cross-reactivity with other 5 viruses.For 28 simulated samples,the integrated assay platform was consistent with the experimental results of reverse transcription-quantitative polymerase chain reaction(RT-qPCR)assays after conventional laboratory nucleic acid extraction.The entire process can be finished in about 1 h,which is ideal for immediate rapid detection.
基金primary financial supports from the National Key R&D Program of China(2021YFA1200102,2021YFA1200101,and 2022YFE0128700)the National Natural Science Foundation of China(22173050,22150013,21727806,and 21933001)+4 种基金the New Cornerstone Science Foundation through the XPLORER PRIZEthe Natural Science Foundation of Beijing(2222009)Beijing National Laboratory for Molecular Sciences(BNLMS202105)the Fundamental Research Funds for the Central Universities(63223056)“Frontiers Science Center for New Organic Matter”at Nankai University(63181206).
文摘Single-molecule junctions,integrating individual molecules as active components between electrodes,serve as fundamental building blocks for advanced electronic and sensing technologies.The application of ionic liquids in single-molecule junctions represents a cutting-edge and rapidly evolving field of research at the intersection of nanoscience,materials chemistry,and electronics.This review explores recent advances where ionic liquids function as electrolytes,dielectric layers,and structural elements within single-molecule junctions,reshaping charge transport,redox reactions,and molecular behaviors in these nanoscale systems.We comprehensively dissect fundamental concepts,techniques,and modulation mechanisms,elucidating the roles of ionic liquids as gates,electrochemical controllers,and interface components in singlemolecule junctions.Encompassing applications from functional device construction to unraveling intricate chemical reactions,this review maps the diverse applications of ionic liquids in single-molecule junctions.Moreover,we propose critical future research topics in this field,including catalysis involving ionic liquids at the single-molecule level,functionalizing single-molecule devices using ionic liquids,and probing the structure and interactions of ionic liquids.These endeavors aim to drive technological breakthroughs in nanotechnology,energy,and quantum research.
基金supported by the CAMS Innovation Fund for Medical Sciences(2016-I2M-3-008,China)National Natural Science Foundation of China(NSFC Nos.81872923 and 81473096)+1 种基金Beijing Natural Science Foundation(No.7172140,China)The Drug Innovation Major Project(No.2018ZX09711001-003,China).
文摘Psoriasis is characterized by abnormal proliferation of keratinocytes,as well as infiltration of immune cells into the dermis and epidermis,causing itchy,scaly and erythematous plaques of skin.The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently.Here,we showed that IMMH002,a novel orally active S1 P1 modulator,desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus.Using different psoriasis animal models,we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PAS I score and pathological injure evaluation.Mechanistically,IMMH002 regulated CD3+T lymphocytes re-distribution by inducing lymphocytes’homing,thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus.Our results suggest that the novel SIP1 agonist,IMMH002,exert extraordinary capacity to rapidly modulate T lymphocytes distribution,representing a promising drug candidate for psoriasis treatment.
基金supported by National Key Research&Development Program from the Ministry of Science and Technology of the PRC(No.2019YFE0111800,China)National Natural Science Foundation of China(No.81872923,China)+1 种基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2021-JKCS-016,China)The Science and Technology Development Fund,Macao SAR(No.0074/2019/AMJ,China).
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.
基金supported by grants from the Natural Science Foundation of China (81760778)the Fundamental Research Funds for Public-interest Scientific Institution in Xinjiang Uygur Autonomous Region (KYGY2016169)CAMS Innovation Fund for Medical Sciences (2017-I2M-1-012)
文摘Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis.Results:Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity,including increasing production of nitric oxide(NO),tumor necrosis factor a(TNFa)and upregulating mRNA levels of inducible NO synthase(iNOS)and TNFa.Furthermore,modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B(NF-κB).Conclusion:The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.
基金supported by International Cooperation and Exchange of the National Natural Science Foundation of China(No.81761168039)Macao Science and TechnologyDevelopment 345 Fund(No.015/2017/AFJ,China)National Key Research and Development Program of China(Nos.2018YFC1704800 and 2018YFC1704805)
文摘Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways,it is still unclear how certain drugs influence these P53 signaling netw orks.Here,we used a comprehensive singlecell multiomics view of the effects of ginsenosides on cancer cells.Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely as sociated with P53 protein.A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins,and proteomemetabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism,amino acid metabolism and"Warburg effect".The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides.Furthermore,by applying affinity mass spectrometry(MS)screening and surface plasmon resonance fragment library screening,we confirmed that 20(S)-protopanaxatriol directly targeted adj acent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions,which further induced a series of omics changes.
文摘The interleukin-1β-mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways are involved in the pathogenesis of rheumatoid arthritis. Ebosin, a novel exopolysaccharide (EPS), exhibits anti-inflammatory activity in rat collagen-induced arthritis by suppressing the production of tumor necrosis factor-s, interleukin-6 and interleukin-1β. The aim of the present study was to assess the effects of ebosin on NF-KB and MAPK signaling pathways mediated through interleukin-1β. in rat fibroblast-like synoviocytes (FLSs). Western blotting showed decreased production of phosphorylated p38, JNK1, JNK2, IKKa, IKKa, and IκB in the cytoplasm and NF-κB in the nucleus upon ebosin treatment. The DNA-binding activity of NF-KB in the cell nucleus was also inhibited by ebosin treatment, as demonstrated using an electrophoresis mobility gel shift assay. Analysis of the results of the immunofluorescence assay also showed a reduced amount of NF-KB in the nucleus of cells affected by ebosin. These results provided evidence for the effects of ebosin on both interleukin-1β-mediated MAPK and NF-κB signaling pathways in rat FLSs. In addition, enzyme-linked immunosorbent assay demonstrated that ebosin reduces the levels of matrix metalloproteinases MMP-1 and MMP-3 and the chemokines, interleukin-8 and RANTES. Thus, the results of the present study provide further evidence for understanding the medicinal activity of ebosin at a molecular level, therefore nominating this EPS as a potential therapeutic candidate for the treatment of rheumatic arthritis.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(2021QZKK0100)the National Key Research and Development Plans(2021YFC0863400)+2 种基金the National Key Research and Development Plans(2021YFC2300904)the National Natural Science Foundation of China General Program(42171144)the National Natural Science Foundation of China for Excellent Young Scientists Fund Program(42222105)。