Soft sensor is an efficacious solution to predict the hard-to-measure target variable by using the process variables.In practical application scenarios, however, the feedback cycle of target variable is usually larger...Soft sensor is an efficacious solution to predict the hard-to-measure target variable by using the process variables.In practical application scenarios, however, the feedback cycle of target variable is usually larger than that of the process variables, which causes the deficiency of prediction errors. Consequently soft sensor cannot be calibrated timely and deteriorates. We proposed a soft sensor calibration method by using Just-in-time modeling and Ada Boost learning method. A moving window consisting of a primary part and a secondary part is constructed.The primary part is made of history data from certain number of constant feedback cycles of target variable and the secondary part includes some coarse target values estimated initially by Just-in-time modeling during the latest feedback cycle of target variable. The data set of the whole moving window is processed by Ada Boost learning method to build an auxiliary estimation model and then target variable values of the latest corresponding feedback cycle are reestimated. Finally the soft sensor model is calibrated by using the reestimated target variable values when the target feedback is unavailable; otherwise using the feedback value. The feasibility and effectiveness of the proposed calibration method is tested and verified through a series of comparative experiments on a pH neutralization facility in our laboratory.展开更多
Chemotherapy remains one of the irreplaceable treatments for cancer therapy.The use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously el...Chemotherapy remains one of the irreplaceable treatments for cancer therapy.The use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B(GrB).However,numerous malignant cancers adaptively acquired the capacity of secreting serpinb9(Sb9),a physiological inhibitor of GrB,which can reversibly inhibit the biological activity of GrB.To circumvent this dilemma,in this study,an integrated tailor-made nanomedicine composed of tumor-targeting peptide(Arg-Gly-Asp,RGD)decorated liposome,doxorubicin(DOX,an effective ICD inducer),and the compound 3034(an inhibitor of Sb9),is developed(termed as D3RL)for breast cancer chemo-immunotherapy.In vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ICD.Meanwhile,D3RL can competitively relieve the inhibition of Sb9 to GrB.The restored GrB can not only effectively induce tumor immunotherapy,but also degrade matrix components in the tumor microenvironment,consequently improving the infiltration of immune cells and the penetration of nanomedicines,which in return enhance the combined antitumor effect.Taken together,this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemo-immunotherapy for breast cancer.展开更多
Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgi...Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after surgery.Here,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies.This study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.展开更多
Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosen...Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.展开更多
基金Supported by the National Basic Research Program of China(2012CB720500)
文摘Soft sensor is an efficacious solution to predict the hard-to-measure target variable by using the process variables.In practical application scenarios, however, the feedback cycle of target variable is usually larger than that of the process variables, which causes the deficiency of prediction errors. Consequently soft sensor cannot be calibrated timely and deteriorates. We proposed a soft sensor calibration method by using Just-in-time modeling and Ada Boost learning method. A moving window consisting of a primary part and a secondary part is constructed.The primary part is made of history data from certain number of constant feedback cycles of target variable and the secondary part includes some coarse target values estimated initially by Just-in-time modeling during the latest feedback cycle of target variable. The data set of the whole moving window is processed by Ada Boost learning method to build an auxiliary estimation model and then target variable values of the latest corresponding feedback cycle are reestimated. Finally the soft sensor model is calibrated by using the reestimated target variable values when the target feedback is unavailable; otherwise using the feedback value. The feasibility and effectiveness of the proposed calibration method is tested and verified through a series of comparative experiments on a pH neutralization facility in our laboratory.
基金supported by grants from the National Natural Science Foundation of China(Nos.32000998,and 32201240)The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(No.2022HYTP046)+2 种基金the China Postdoctoral Science Foundation(Nos.2019TQ0285,2019M662513,and 2021TQ0298)Henan provincial Medical Science and Technology Research Project(No.LHGJ20210210)Science and Technology Development Project of Henan Province(Nos.212102310138 and 222102310525).
文摘Chemotherapy remains one of the irreplaceable treatments for cancer therapy.The use of immunogenic cell death(ICD)-inducing chemotherapeutic drugs offers a practical strategy for killing cancer cells,simultaneously eliciting an antitumor immune response by promoting the recruitment of cytotoxic immune cells and production of granzyme B(GrB).However,numerous malignant cancers adaptively acquired the capacity of secreting serpinb9(Sb9),a physiological inhibitor of GrB,which can reversibly inhibit the biological activity of GrB.To circumvent this dilemma,in this study,an integrated tailor-made nanomedicine composed of tumor-targeting peptide(Arg-Gly-Asp,RGD)decorated liposome,doxorubicin(DOX,an effective ICD inducer),and the compound 3034(an inhibitor of Sb9),is developed(termed as D3RL)for breast cancer chemo-immunotherapy.In vitro and in vivo studies show that D3RL can directly kill tumor cells and trigger the host immune response by inducing ICD.Meanwhile,D3RL can competitively relieve the inhibition of Sb9 to GrB.The restored GrB can not only effectively induce tumor immunotherapy,but also degrade matrix components in the tumor microenvironment,consequently improving the infiltration of immune cells and the penetration of nanomedicines,which in return enhance the combined antitumor effect.Taken together,this work develops an integrated therapeutic solution for targeted production and restoration of GrB to achieve a combined chemo-immunotherapy for breast cancer.
基金the National Natural Science Foundation of China(Nos.32000998 and U2004123)the Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(No.2022HYTP046)the China Postdoctoral Science Foundation(Nos.2019TQ0285,2019M662513,2021TQ0298,and 2022TQ0296).
文摘Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after surgery.Here,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies.This study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.
基金supported by grants from the National Basic Research Plan of China(grant no.2018YFA0208900)the National Natural Science Foundation of China(grant nos.32000998,32000996,,U2004123)+1 种基金The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(grant no.2022HYTP046)the China Postdoctoral Science Foundation(grant nos.2019TQ0285,2019M662513,2020M682358,2020TQ0280,2021TQ0298).
文摘Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.
