The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment...The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection.However,their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity.Herein,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin(ISL)loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug(ISL-G2)bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized oligochitosan.The obtained ISL-G2loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr)binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs.The NPs maintained their negatively charged surface,thus prolonging the blood circulation time.In response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the biofilms.Sequentially,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA.An in vivo study was performed on a MRSA biofilm infected wound model.This phytochemical-based system led to~2log CFU(>99%)reduction of biofilm MRSA as compared to untreated wound(P<0.001)with negligible biotoxicity in mice.This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.展开更多
BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an ...BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an essential physiological process that occurs during embryonic development and tissue regeneration.Angiogenesis is the growth of new capillaries from pre-existing blood vessels,which is observed both prenatally and postnatally.The placenta is an organ composed of a variety of fetal-derived cells,including ECFCs,and therefore has significant potential as a source of fetal ECFCs for tissue engineering.AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi(CV-ECFCs)of the placenta,and assess their potential for tissue engineering.METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion.Cells expressing CD31 were selected using magnetic-activated cell sorting,and plated in endothelial-specific growth medium.After 2-3 wks in culture,colonies displaying cobblestone-like morphology were manually picked using cloning cylinders.We characterized CV-ECFCs by flow cytometry,immunophenotyping,tube formation assay,and Dil-Ac-LDL uptake assay.Viral transduction of CVECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector,and transduction efficiency was tested by fluorescent microscopy and flow cytometry.Compatibility of CV-ECFCs with a delivery vehicle was determined using an FDA approved,small intestinal submucosa extracellular matrix scaffold.RESULTS After four passages in 6-8 wks of culture,we obtained a total number of 1.8×107 CV-ECFCs using 100 mg of early gestational chorionic villus tissue.Immunophenotypic analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31,CD144,CD146,CD105,CD309,only partially expressed CD34,and did not express CD45 and CD90.CV-ECFCs were capable of acetylated low-density lipoprotein uptake and tube formation,similar to cord blood-derived ECFCs(CB-ECFCs).CV-ECFCs can be transduced with a Luciferase/tdTomato-containing lentiviral vector at a transduction efficiency of 85.1%.Seeding CV-ECFCs on a small intestinal submucosa extracellular matrix scaffold confirmed that CV-ECFCs were compatible with the biomaterial scaffold.CONCLUSION In summary,we established a magnetic sorting-assisted clonal isolation approach to derive CV-ECFCs.A substantial number of CV-ECFCs can be obtained within a short time frame,representing a promising novel source of ECFCs for fetal treatments.展开更多
The temporal evolution of extreme ultraviolet(EUV)emission spectra of laser-produced antimony(Sb)plasmas has been measured in the 7-16 nm wavelength region using spatio?temporally resolved lase-produced plasma spectro...The temporal evolution of extreme ultraviolet(EUV)emission spectra of laser-produced antimony(Sb)plasmas has been measured in the 7-16 nm wavelength region using spatio?temporally resolved lase-produced plasma spectroscopy technique.The spectral profiles involve an intense quasi-continuous band with superimposed intense characteristic radiation and are different with the increase of delay time.The spectral structures were also analyzed according to Hartree-Fock calculations with configuration interaction effects and contributed from 4d^4/;4d-4p,and 4d-5f unresolved transition arrays of Sb7*-Sb131.A steady-state collisionalradiative model was used to estimate the electron temperature and density range of Sb plasmas.This work would enrich the spectral data of highly-charged ions and provided a possible selection for developing EUV light sources.展开更多
In order to provide detailed information about Cd structure and gain more insight regarding ionization degrees and types of transition,as well as the understanding of the temporal evolution behavior of laser produced ...In order to provide detailed information about Cd structure and gain more insight regarding ionization degrees and types of transition,as well as the understanding of the temporal evolution behavior of laser produced Cd plasmas,extreme ultraviolet spectra of laser-produced cadmium(Cd)plasmas have been measured in the 8.4-12 nm region using spatiotemporally resolved laser-produced plasma spectroscopy technique.Spectral features were analyzed by the Hartree-Fock(HF)method with relativistic correlations(HFR)using the Cowan code.The results showed that the 4p-5s resonance transition arrays from Cd^9+to Cd^13+merged to form intense lines in this spectral region.A number of new spectral features from Cd^9+and Cd^10+ions are reported in this study.Based on the assumption of a normalized Boltzmann distribution among the excited states associated with a steady-state collisional-radiative model,the plasma parameters were obtained by comparing the experimental and simulated spectra.As a result,we succeeded in reproducing the synthetic spectra for different time delays,which yielded good agreement with the experiments.The temporal evolution behaviors of electron temperature and electron density of plasma were also analyzed.展开更多
Armed with four different steady-state collisional-radiative(CR) models,we investigated the effect of dielectronic recombination(DR) on the charge-state distribution in laser-produced silicon plasma. To assess this ef...Armed with four different steady-state collisional-radiative(CR) models,we investigated the effect of dielectronic recombination(DR) on the charge-state distribution in laser-produced silicon plasma. To assess this effect,we performed a series of temporally resolved spectra of highly charged Si ions in the extreme ultraviolet region.Ab initio calculations of the DR rate coefficients were done for Si^(6+)–Si^(4+) ions. We also analyzed the evolution of the collisional ionization, radiative recombination, three-body recombination, photo-ionization, and DR rate coefficients as a function of electron temperature. The electron temperature and electron density for different delay times were obtained by comparing the normalized experimental and simulated spectra. The ion fraction and average charge state from the four different CR models were also obtained. The results indicate that the DR process has a greater influence in the stage of plasma evolution that cannot be neglected in plasma diagnoses.展开更多
Diabetic ischemic wound treatment remains a critical clinical challenge.Neovascularization plays a significant role in wound healing during all stages of the tissue repair process.Strategies that enhance angiogenesis ...Diabetic ischemic wound treatment remains a critical clinical challenge.Neovascularization plays a significant role in wound healing during all stages of the tissue repair process.Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds,particularly diabetic wounds in highly ischemic conditions.We previously identified a cyclic peptide LXW7 that specifically binds to integrinαvβ3 on endothelial progenitor cells(EPCs)and endothelial cells(ECs),activates vascular endothelial growth factor(VEGF)receptors,and promotes EC growth and maturation.In this study,we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides(SILY)to a dermatan sulfate(DS)glycosaminoglycan backbone,named LXW7-DS-SILY,and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix(ECM)scaffolds.We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment.When applied in an established Zucker Diabetic Fatty(ZDF)rat ischemic skin flap model,LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing,enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment.Altogether,this study provides a promising novel treatment to accelerate diabetic ischemic wound healing,thereby reducing limb amputation and mortality of diabetic patients.展开更多
The standard of care for early or locally advanced rectal cancer is promoted by multiple clinical practice guidelines globally,but the considerable differences between the guidelines may cause confusion.We compared th...The standard of care for early or locally advanced rectal cancer is promoted by multiple clinical practice guidelines globally,but the considerable differences between the guidelines may cause confusion.We compared the latest updated clinical practice guidelines from five professional societies/authorities:National Comprehensive Cancer Network,American Society of Colorectal Surgeons,European Society of Medical Oncology,Chinese National Health Commission,and Chinese Society of Clinical Oncology.Key evidence is discussed for a better understanding of some seemingly contradictory recommendations.展开更多
基金supported by the National Natural Science Foundation of China(No.3210190403)the Natural Science Foundation of Heilongjiang Province(No.YQ2022C016)+2 种基金the China Postdoctoral Science Foundation(2022T150104and 2020M670877)the Postdoctoral Science Foundation of Heilongjiang Province(LBH-TZ2104 and LBH-Z20039)the China Agriculture Research System of MOF and MARA(No.CARS-35)。
文摘The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection.However,their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity.Herein,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin(ISL)loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug(ISL-G2)bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized oligochitosan.The obtained ISL-G2loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr)binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs.The NPs maintained their negatively charged surface,thus prolonging the blood circulation time.In response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the biofilms.Sequentially,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA.An in vivo study was performed on a MRSA biofilm infected wound model.This phytochemical-based system led to~2log CFU(>99%)reduction of biofilm MRSA as compared to untreated wound(P<0.001)with negligible biotoxicity in mice.This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.
基金the Shriners Hospital for Children Postdoctoral Research Fellowship award,No.84704-NCA-19UC Davis School of Medicine Dean’s Fellowship award and funding from the NIH,No.5R01NS100761-02 and No.R03HD091601-01+2 种基金the California Institute of Regenerative Medicine,No.PC1-08103 and No.CLIN1-11404Shriners Hospitals for Children,No.85120-NCA-16,No.85119-NCA-18,No.85108-NCA-19 and No.87200-NCA-19March of Dimes Foundation,No.5FY1682
文摘BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an essential physiological process that occurs during embryonic development and tissue regeneration.Angiogenesis is the growth of new capillaries from pre-existing blood vessels,which is observed both prenatally and postnatally.The placenta is an organ composed of a variety of fetal-derived cells,including ECFCs,and therefore has significant potential as a source of fetal ECFCs for tissue engineering.AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi(CV-ECFCs)of the placenta,and assess their potential for tissue engineering.METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion.Cells expressing CD31 were selected using magnetic-activated cell sorting,and plated in endothelial-specific growth medium.After 2-3 wks in culture,colonies displaying cobblestone-like morphology were manually picked using cloning cylinders.We characterized CV-ECFCs by flow cytometry,immunophenotyping,tube formation assay,and Dil-Ac-LDL uptake assay.Viral transduction of CVECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector,and transduction efficiency was tested by fluorescent microscopy and flow cytometry.Compatibility of CV-ECFCs with a delivery vehicle was determined using an FDA approved,small intestinal submucosa extracellular matrix scaffold.RESULTS After four passages in 6-8 wks of culture,we obtained a total number of 1.8×107 CV-ECFCs using 100 mg of early gestational chorionic villus tissue.Immunophenotypic analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31,CD144,CD146,CD105,CD309,only partially expressed CD34,and did not express CD45 and CD90.CV-ECFCs were capable of acetylated low-density lipoprotein uptake and tube formation,similar to cord blood-derived ECFCs(CB-ECFCs).CV-ECFCs can be transduced with a Luciferase/tdTomato-containing lentiviral vector at a transduction efficiency of 85.1%.Seeding CV-ECFCs on a small intestinal submucosa extracellular matrix scaffold confirmed that CV-ECFCs were compatible with the biomaterial scaffold.CONCLUSION In summary,we established a magnetic sorting-assisted clonal isolation approach to derive CV-ECFCs.A substantial number of CV-ECFCs can be obtained within a short time frame,representing a promising novel source of ECFCs for fetal treatments.
文摘The temporal evolution of extreme ultraviolet(EUV)emission spectra of laser-produced antimony(Sb)plasmas has been measured in the 7-16 nm wavelength region using spatio?temporally resolved lase-produced plasma spectroscopy technique.The spectral profiles involve an intense quasi-continuous band with superimposed intense characteristic radiation and are different with the increase of delay time.The spectral structures were also analyzed according to Hartree-Fock calculations with configuration interaction effects and contributed from 4d^4/;4d-4p,and 4d-5f unresolved transition arrays of Sb7*-Sb131.A steady-state collisionalradiative model was used to estimate the electron temperature and density range of Sb plasmas.This work would enrich the spectral data of highly-charged ions and provided a possible selection for developing EUV light sources.
基金Project supported by the National Key Research and Development Program of China(Grant No.2017YFA0402300)the National Natural Science Foundation of China(Grant Nos.11874051,11904293,and 61965015)the Special Fund Project for Guiding Scientific and Technological Innovation of Gansu Province,China(Grant No.2019zx-10).
文摘In order to provide detailed information about Cd structure and gain more insight regarding ionization degrees and types of transition,as well as the understanding of the temporal evolution behavior of laser produced Cd plasmas,extreme ultraviolet spectra of laser-produced cadmium(Cd)plasmas have been measured in the 8.4-12 nm region using spatiotemporally resolved laser-produced plasma spectroscopy technique.Spectral features were analyzed by the Hartree-Fock(HF)method with relativistic correlations(HFR)using the Cowan code.The results showed that the 4p-5s resonance transition arrays from Cd^9+to Cd^13+merged to form intense lines in this spectral region.A number of new spectral features from Cd^9+and Cd^10+ions are reported in this study.Based on the assumption of a normalized Boltzmann distribution among the excited states associated with a steady-state collisional-radiative model,the plasma parameters were obtained by comparing the experimental and simulated spectra.As a result,we succeeded in reproducing the synthetic spectra for different time delays,which yielded good agreement with the experiments.The temporal evolution behaviors of electron temperature and electron density of plasma were also analyzed.
基金supported by the National Key Research and Development Program of China (Grant No. 2017YFA0402300)National Natural Science Foundation of China (NSFC) (Grant Nos. 11904293, 11874051)。
文摘Armed with four different steady-state collisional-radiative(CR) models,we investigated the effect of dielectronic recombination(DR) on the charge-state distribution in laser-produced silicon plasma. To assess this effect,we performed a series of temporally resolved spectra of highly charged Si ions in the extreme ultraviolet region.Ab initio calculations of the DR rate coefficients were done for Si^(6+)–Si^(4+) ions. We also analyzed the evolution of the collisional ionization, radiative recombination, three-body recombination, photo-ionization, and DR rate coefficients as a function of electron temperature. The electron temperature and electron density for different delay times were obtained by comparing the normalized experimental and simulated spectra. The ion fraction and average charge state from the four different CR models were also obtained. The results indicate that the DR process has a greater influence in the stage of plasma evolution that cannot be neglected in plasma diagnoses.
基金partially supported by California Institute for Regenerative Medicine[grant number DISC1-10516-0]Shriners Hospitals for Children developmental research award[grant number 87200-NCA-19]supported by NCI P30CA093373 Cancer Center Support Grant.
文摘Diabetic ischemic wound treatment remains a critical clinical challenge.Neovascularization plays a significant role in wound healing during all stages of the tissue repair process.Strategies that enhance angiogenesis and neovascularization and improve ischemic pathology may promote the healing of poor wounds,particularly diabetic wounds in highly ischemic conditions.We previously identified a cyclic peptide LXW7 that specifically binds to integrinαvβ3 on endothelial progenitor cells(EPCs)and endothelial cells(ECs),activates vascular endothelial growth factor(VEGF)receptors,and promotes EC growth and maturation.In this study,we designed and synthesized a multi-functional pro-angiogenic molecule by grafting LXW7 and collagen-binding peptides(SILY)to a dermatan sulfate(DS)glycosaminoglycan backbone,named LXW7-DS-SILY,and further employed this multi-functional molecule to functionalize collagen-based extracellular matrix(ECM)scaffolds.We confirmed that LXW7-DS-SILY modification significantly promoted EPC attachment and growth on the ECM scaffolds in vitro and supported EPC survival in vivo in the ischemic environment.When applied in an established Zucker Diabetic Fatty(ZDF)rat ischemic skin flap model,LXW7-DS-SILY-functionalized ECM scaffolds loaded with EPCs significantly improved wound healing,enhanced neovascularization and modulated collagen fibrillogenesis in the ischemic environment.Altogether,this study provides a promising novel treatment to accelerate diabetic ischemic wound healing,thereby reducing limb amputation and mortality of diabetic patients.
文摘The standard of care for early or locally advanced rectal cancer is promoted by multiple clinical practice guidelines globally,but the considerable differences between the guidelines may cause confusion.We compared the latest updated clinical practice guidelines from five professional societies/authorities:National Comprehensive Cancer Network,American Society of Colorectal Surgeons,European Society of Medical Oncology,Chinese National Health Commission,and Chinese Society of Clinical Oncology.Key evidence is discussed for a better understanding of some seemingly contradictory recommendations.
