In the context of global COVID-19 epidemic preparedness,the extensive use of disposable surgical masks(DSM)may lead to its emergence as a main new source of microplastics in the environment.Nowadays,DSMs have become a...In the context of global COVID-19 epidemic preparedness,the extensive use of disposable surgical masks(DSM)may lead to its emergence as a main new source of microplastics in the environment.Nowadays,DSMs have become a non-negligible source of plastic waste in aquatic environment,however,less research has been done on DSM after biofilm colonization in freshwater environment.The study investigated the microbial community of DSM-associated biofilms by 16S rRNA gene sequencing.Analysis of the microbial community in the middle and inner/outer layers of the DSM showed that the middle layer was different from the remaining two layers and that potential pathogens were enriched only in the middle layer of the DSM.Herein,we focused on the middle layer and explored the characterization properties and extracellular polymeric substances(EPS)components changes during biofilm formation.The results showed that the EPS components varied with the biofilm incubation time.As the formation of biofilm,the protein(PN)and polysaccharide(PS)in EPS showed an overall increasing trend,and the growth of PS was well synchronized with PN.Three fluorescent components of EPS were determined by the three-dimensional excitation emission matrix(3D-EEM),including humic acid-like,fulvic acid-like,and aromatic protein-like components.The percentage of fluorescent components varied with increasing biofilm development time and then stabilized.Fourier transform infrared spectroscopy(FTIR)characterization results elucidated the emergence of oxygen-containing functional groups during biofilm formation.Moreover,the hydrophilicity increased with biofilm development.In conclusion,the environmental behavior and ecological risks of DSM in aquatic environment deserve urgent attention in future studies.展开更多
Osteoporosis is a degenerative disease caused by an imbalance between osteoblast and osteoclast activity.Repairing osteo-porotic bone defects is challenging due to decreased osteogenesis,increased osteoclast activity,...Osteoporosis is a degenerative disease caused by an imbalance between osteoblast and osteoclast activity.Repairing osteo-porotic bone defects is challenging due to decreased osteogenesis,increased osteoclast activity,and impaired angiogenesis.To address this challenge,a novel scaffold,inspired by the structure of multilayer fishing nets,is developed through a com-bination of template-assisted electrospinning and advanced three-dimensional(3D)printing technologies.The 3D nanofiber scaffold exhibits a hierarchical porous architecture.This design maintains the high specific surface area and extracellular matrix(ECM)mimicry of the nanofiber membrane.Additionally,the sparsely distributed nanofibers within the mesh-like structure facilitate cell infiltration.This unique topological configuration,particularly the strontium-hydroxyapatite(Sr-HAp)-enriched polycaprolactone/silk fibroin nanofibers,plays a critical role in synergistically promoting angiogenesis,enhancing osteogenesis,and suppressing osteoclast differentiation.In an osteoporotic cranial bone defect model,the scaffold demonstrates an exceptional repair efficiency of nearly 100%within 8 weeks,marked by significant new bone formation throughout the implanted area.In conclusion,our approach,which leverages intricate biomimicry and strategic active ion release,emerges as a highly promising strategy for repairing osteoporotic bone defects.展开更多
The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for ...The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 （osimertinib; Tagrisso） is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.展开更多
基金Supported by the Natural Science Foundation of Shandong Province(Nos.ZR2022MD115,ZR202111160067)。
文摘In the context of global COVID-19 epidemic preparedness,the extensive use of disposable surgical masks(DSM)may lead to its emergence as a main new source of microplastics in the environment.Nowadays,DSMs have become a non-negligible source of plastic waste in aquatic environment,however,less research has been done on DSM after biofilm colonization in freshwater environment.The study investigated the microbial community of DSM-associated biofilms by 16S rRNA gene sequencing.Analysis of the microbial community in the middle and inner/outer layers of the DSM showed that the middle layer was different from the remaining two layers and that potential pathogens were enriched only in the middle layer of the DSM.Herein,we focused on the middle layer and explored the characterization properties and extracellular polymeric substances(EPS)components changes during biofilm formation.The results showed that the EPS components varied with the biofilm incubation time.As the formation of biofilm,the protein(PN)and polysaccharide(PS)in EPS showed an overall increasing trend,and the growth of PS was well synchronized with PN.Three fluorescent components of EPS were determined by the three-dimensional excitation emission matrix(3D-EEM),including humic acid-like,fulvic acid-like,and aromatic protein-like components.The percentage of fluorescent components varied with increasing biofilm development time and then stabilized.Fourier transform infrared spectroscopy(FTIR)characterization results elucidated the emergence of oxygen-containing functional groups during biofilm formation.Moreover,the hydrophilicity increased with biofilm development.In conclusion,the environmental behavior and ecological risks of DSM in aquatic environment deserve urgent attention in future studies.
基金supported by the Program of Excellent Doctoral(Postdoctoral)of Zhongnan Hospital of Wuhan University(Grant No.ZNYB2021005)the Fundamental Research Funds for the Central Universities(2042022kf1121)National Natural Science Foundation of China(Grant No.32101084).
文摘Osteoporosis is a degenerative disease caused by an imbalance between osteoblast and osteoclast activity.Repairing osteo-porotic bone defects is challenging due to decreased osteogenesis,increased osteoclast activity,and impaired angiogenesis.To address this challenge,a novel scaffold,inspired by the structure of multilayer fishing nets,is developed through a com-bination of template-assisted electrospinning and advanced three-dimensional(3D)printing technologies.The 3D nanofiber scaffold exhibits a hierarchical porous architecture.This design maintains the high specific surface area and extracellular matrix(ECM)mimicry of the nanofiber membrane.Additionally,the sparsely distributed nanofibers within the mesh-like structure facilitate cell infiltration.This unique topological configuration,particularly the strontium-hydroxyapatite(Sr-HAp)-enriched polycaprolactone/silk fibroin nanofibers,plays a critical role in synergistically promoting angiogenesis,enhancing osteogenesis,and suppressing osteoclast differentiation.In an osteoporotic cranial bone defect model,the scaffold demonstrates an exceptional repair efficiency of nearly 100%within 8 weeks,marked by significant new bone formation throughout the implanted area.In conclusion,our approach,which leverages intricate biomimicry and strategic active ion release,emerges as a highly promising strategy for repairing osteoporotic bone defects.
基金This project was partially supported by the National Natural Science Foundation of China （No. 81101726）. Shuhang Wang was a recipient of the CAHON Young Investigator Award （www.cahon. org）.
文摘The tyrosine kinase inhibitors （TKI） of the epidermal growth factor receptor （EGFR） are becoming the first line of therapy for advanced non-small cell lung cancer （NSCLC）. Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 （osimertinib; Tagrisso） is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.
