With the increasing resistance of Streptococcus pneumoniae(S.pneumoniae)toβ-lactam antibiotics(BLAs),combination therapy has become an effective strategy to address this challenge.This study evaluated the inhibitory ...With the increasing resistance of Streptococcus pneumoniae(S.pneumoniae)toβ-lactam antibiotics(BLAs),combination therapy has become an effective strategy to address this challenge.This study evaluated the inhibitory activity of ten natural medicines against S.pneumoniae using in vitro antibacterial assays.Seven herbs,including Galla chinensis,Coptidis rhizoma,Scutellaria baicalensis,Phellodendri chinensis cortex,Sophora flavescens,Salviae miltiorrhizae radix et rhizoma,and Houttuynia cordata Thunb,were found to be effective,with Coptidis rhizoma,Scutellaria baicalensis,and Phellodendri chinensis cortex showing the most significant activity.Additionally,surface plasmon resonance(SPR)technology was employed to couple the PBP3 target to a CM5 chip for target-guided fishing of potential active compounds and evaluation of their PBP3-binding capabilities.The ethanol extract of Scutellaria baicalensis exhibited the highest binding response,reaching 20,000 RU.The targetbound components were eluted and identified by UPLC-MS,confirming Oroxindin as the most potent target compound.Its dissociation constant(KD)with PBP3 was determined to be 5.049×10^(-7) mol/L,indicating stable binding and high affinity.Finally,it is noteworthy that in vitro antibacterial assays demonstrated a significant enhancement of antibiotic efficacy by Oroxindin:co-administration with cefquinome(CEF)reduced the mini-mum inhibitory concentration(MIC)for S.pneumoniae from 32μg/mL to 1μg/mL(a 32-fold increase in sensitivity),while co-administration with ampicillin(AMP)reduced the MIC from 32μg/mL to 0.5μg/mL(a 64-fold increase in sensitivity).This study identified and validated the sensitizing efficacy of Oroxindin in inhibiting S.pneumoniae,providing a new approach to addressing BLAs resistance and laying a foundation for mechanistic research and clinical translation of combination therapy strategies.展开更多
Prosthesis implantation and fat transplantation are common breast reconstructionmethods.In general,prosthesis implantation alone does not achieve a realistic enough appearance,and fat transplantation alone is difficul...Prosthesis implantation and fat transplantation are common breast reconstructionmethods.In general,prosthesis implantation alone does not achieve a realistic enough appearance,and fat transplantation alone is difficult to achieve in the correct capacity.To date,no reports have focused on methods of combining fat with implanted prostheses for breast reconstruction.Using a newly designed bionic ink(i.e.,polyether F127 diacrylate(F127DA)&poly(ethylene glycol)diacrylate(PEGDA))and projection-based three-dimensional bioprinting(PBP),we report the development of a new method for printing porous prostheses.PEGDA was used to improve the printing precision of the prosthesis by increasing the gel point of F127DA and reducing the impact of external temperature.The compression modulus of the printed prosthesis was very close to that of prostheses currently used in clinical practice and to that of natural breasts.Finally,stromal vascular fraction gel(SVF-gel),a human fat extract,was injected into the pores of the synthesized prostheses to prepare a prosthesis mixed with adipose tissue.These were implanted subcutaneously in nude mice to observe their biological performance.After 14 and 28 days of observation,the prosthesis showed good biocompatibility,and adipose tissues grew well in and around the prosthesis.This result shows that a porous prosthesis containing pre-placed adipose tissues is a promising breast reconstruction material.展开更多
Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes ametho...Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.展开更多
基金the Shaanxi Provincial Department of Science and Tech-nology Project(No.2023-CX-PT-24,No.2023-YBSF-017)the Key Research and Development Program of Shaanxi Province(No.2024SFZDCYL-02-13)Qinba Bioresources and Ecological Environment National Key Laboratory(No.SLGPT2019KF04-05).
文摘With the increasing resistance of Streptococcus pneumoniae(S.pneumoniae)toβ-lactam antibiotics(BLAs),combination therapy has become an effective strategy to address this challenge.This study evaluated the inhibitory activity of ten natural medicines against S.pneumoniae using in vitro antibacterial assays.Seven herbs,including Galla chinensis,Coptidis rhizoma,Scutellaria baicalensis,Phellodendri chinensis cortex,Sophora flavescens,Salviae miltiorrhizae radix et rhizoma,and Houttuynia cordata Thunb,were found to be effective,with Coptidis rhizoma,Scutellaria baicalensis,and Phellodendri chinensis cortex showing the most significant activity.Additionally,surface plasmon resonance(SPR)technology was employed to couple the PBP3 target to a CM5 chip for target-guided fishing of potential active compounds and evaluation of their PBP3-binding capabilities.The ethanol extract of Scutellaria baicalensis exhibited the highest binding response,reaching 20,000 RU.The targetbound components were eluted and identified by UPLC-MS,confirming Oroxindin as the most potent target compound.Its dissociation constant(KD)with PBP3 was determined to be 5.049×10^(-7) mol/L,indicating stable binding and high affinity.Finally,it is noteworthy that in vitro antibacterial assays demonstrated a significant enhancement of antibiotic efficacy by Oroxindin:co-administration with cefquinome(CEF)reduced the mini-mum inhibitory concentration(MIC)for S.pneumoniae from 32μg/mL to 1μg/mL(a 32-fold increase in sensitivity),while co-administration with ampicillin(AMP)reduced the MIC from 32μg/mL to 0.5μg/mL(a 64-fold increase in sensitivity).This study identified and validated the sensitizing efficacy of Oroxindin in inhibiting S.pneumoniae,providing a new approach to addressing BLAs resistance and laying a foundation for mechanistic research and clinical translation of combination therapy strategies.
基金This work was supported by the National Key Research andDevelopment Program of China(No.2018YFA0703000)the National Natural Science Foundation of China(Nos.T2121004,52235007,and 82203602)+2 种基金Zhejiang Provincial Natural Science Foundation of China under Grant No.LQ22H160020 to JWThis work was also supported by Start-up Funding of Zhejiang Provincial People’s Hospital(No.ZRY2021A001 to JW)Basic Scientific Research Funds of Department of Education of Zhejiang Province(No.KYQN202109 to JW).
文摘Prosthesis implantation and fat transplantation are common breast reconstructionmethods.In general,prosthesis implantation alone does not achieve a realistic enough appearance,and fat transplantation alone is difficult to achieve in the correct capacity.To date,no reports have focused on methods of combining fat with implanted prostheses for breast reconstruction.Using a newly designed bionic ink(i.e.,polyether F127 diacrylate(F127DA)&poly(ethylene glycol)diacrylate(PEGDA))and projection-based three-dimensional bioprinting(PBP),we report the development of a new method for printing porous prostheses.PEGDA was used to improve the printing precision of the prosthesis by increasing the gel point of F127DA and reducing the impact of external temperature.The compression modulus of the printed prosthesis was very close to that of prostheses currently used in clinical practice and to that of natural breasts.Finally,stromal vascular fraction gel(SVF-gel),a human fat extract,was injected into the pores of the synthesized prostheses to prepare a prosthesis mixed with adipose tissue.These were implanted subcutaneously in nude mice to observe their biological performance.After 14 and 28 days of observation,the prosthesis showed good biocompatibility,and adipose tissues grew well in and around the prosthesis.This result shows that a porous prosthesis containing pre-placed adipose tissues is a promising breast reconstruction material.
基金sponsored by the National Natural Science Foundation of China(No.52235007,YH)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.T2121004,YH)+3 种基金the NationalNatural Science Foundation of China(No.52305300,MJX)the Fellowship of China Postdoctoral Science Foundation(No.2022M722826,MJX)the National Natural Science Foundation of China(No.82203602,JW)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H160020,JW)。
文摘Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.
