目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase-like orphan rectetpor 1,ROR1)在不同病理亚型肺腺癌组织中的表达与气腔播散(spread through air space,STAS)发生的关系。方法收集昆明医科大学第一附属医院病理科2017年...目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase-like orphan rectetpor 1,ROR1)在不同病理亚型肺腺癌组织中的表达与气腔播散(spread through air space,STAS)发生的关系。方法收集昆明医科大学第一附属医院病理科2017年6月至2022年1月,肺腺癌组织蜡块标本618例,采用HE染色切片判断病理亚型与病理特征,记数STAS数量并分级,免疫组化染色,半定量判读ROR1表达水平,统计分析ROR1表达与STAS数量及与病理亚型的关系。结果ROR1在微乳头型与实体型肺腺癌(低分化)中的表达高于其它亚型肺腺癌,差异有统计学意义(P<0.001);ROR1在低STAS、高STAS组中表达率分别为88.0%、94.1%,高于无STAS组且差异有统计学意义(P<0.001)。结论ROR1高表达于低分化肺腺癌并提示更高的STAS发生率。ROR1有望成为新的肺腺癌诊断生物标志物用于指导临床治疗及辅助预后判断,并可能成为STAS阳性肺腺癌的潜在治疗靶点。展开更多
With the leaves,bark and roots of Liriodendron chinense Sarg.× L.tulipifera L.as experiment materials,the ultrasonic-assisted extraction conditions of total flavonoids were optimized by response surface Box-Behnk...With the leaves,bark and roots of Liriodendron chinense Sarg.× L.tulipifera L.as experiment materials,the ultrasonic-assisted extraction conditions of total flavonoids were optimized by response surface Box-Behnken test design.Ultrasonic time and liquid-to-solid ratio had significant effects on the extraction amount of flavonoids from the leaves of L.chinense Sarg.× L.tulipifera L.;ultrasonic temperature and liquid-to-solid ratio had an interaction on the extraction amount of flavonoids;and the optimum ultrasonic time,temperature and liquid-to-solid ratio for the extraction of flavonoids from leaves of L.chinense Sarg.× L.tulipifera L.were 19.82 min,28.60 ℃ and 9.48 ml/g,respectively.Ultrasonic time,temperature and liquid-to-solid ratio had significant effects on the extraction amount of flavonoids from L.chinense Sarg.× L.tulipifera L.;there was a significant interaction between any two of the factors,which had a significant effect on the extraction of flavonoids;and the optimum extraction parameters for flavonoids in the bark were the ultrasonic time of 33.66 min,the ultrasonic temperature at 32.85 ℃ and the liquid-to-solid ratio of 11.39 ml/g.Ultrasonic time and liquid-to-solid ratio had significant effects on the extraction of flavonoids from roots;there was a significant interaction between ultrasonic time and liquid-to-solid ratio and between ultrasonic temperature and liquid-to-solid ratio;and the optimum extraction parameters for flavonoids from the roots of L.chinense Sarg.× L.tulipifera L.were the ultrasonic time of 32.38 min,the ultrasonic temperature at 25.0 ℃ and the liquid-to-solid ratio of 8.00 ml/g.The results of the three models were stable.The models are feasible and have good application value.展开更多
With continuously increasing of photovoltaic (PV) plant’s penetration, it has become a critical issue to improve the fault ride-through capability of PV plant. This paper refers to the German grid code, and the PV sy...With continuously increasing of photovoltaic (PV) plant’s penetration, it has become a critical issue to improve the fault ride-through capability of PV plant. This paper refers to the German grid code, and the PV system is controlled to keep grid connected, as well as inject reactive current to grid when fault occurs. The mathematical model of PV system is established and the fault characteristic is studied with respect to the control strategy. By analyzing the effect of reactive power supplied by the PV system to the point of common coupling (PCC) voltage, this paper proposes an adaptive voltage support control strategy to enhance the fault ride-through capability of PV system. The control strategy fully utilizes the PV system’s capability of voltage support and takes the safety of equipment into account as well. At last, the proposed control strategy is verified by simulation.展开更多
Microsporidia are a group of intracelluar eukaryotic parasites,which can infected almost all animals,including human beings.Till now,no mitochodria but mitosome,a remnant of mitochondria was discovered in this phylum....Microsporidia are a group of intracelluar eukaryotic parasites,which can infected almost all animals,including human beings.Till now,no mitochodria but mitosome,a remnant of mitochondria was discovered in this phylum.We present here the mitochondrial pyruvate dehydrogenase E1(PDH,including PDHα and PDHβ)of the microsporidian Nosema bombycis,the pathogen of silkworm pébrine.Compared with PDH of microsporidian Encephalitozoon cuniculi and Antonospora locustae,both subunits are conserved.The phylogeny indicated that both subunits are mitochondrial.The syntenic maps revealed the subunits organization of NbPDH is distributed in different scaffolds,similar to that of EcPDH but different with AlPDH,and the relationship between phylogeny tree and organization of PDH suggest that the AlPDH subunits organization is the ancestral style of microsporidia,and through the genome evolution,the reshuffling of the chromosome of microsporidia occurred,the adjacent style of ALPDHE1 organization changed,and the two subunits separated and located to different chromosomes in E.cuniculi.For N.bombycis and N.ceranae,they locate to different scaffolds.In order to determine NbPDH subcellular localizations,we prepared the polyclonal antibodies against NbPDH prokaryotic fusion proteins,and adopted the colloidal gold immunological electron microscopy,the expression signals of NbPDH were observed in spores however,the subcellular localization were not definited.In general,through comparison of three microsporidian PDH molecular phylogeny,subunits organization in chromosomes,localization indicated that PDH is an interesting marker in microsporidia evolution.展开更多
Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while ...Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.展开更多
Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction.Conventional approaches can regulate bone homeostasis to a certain extent.However,these therapies a...Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction.Conventional approaches can regulate bone homeostasis to a certain extent.However,these therapies are still associated with some undesirable problems.Fortunately,recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related diseases.This review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related diseases.First,the potential utility of nanomaterials for biological imaging and biomarker detection is illustrated.Second,nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are highlighted.Finally,perspectives in this field are offered,including current key bottlenecks and future directions,which may be helpful for exploiting nanomaterials with novel properties and unique functions.This review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases.展开更多
For patients with osteoporosis,the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation,migration,and osteogenic differentiation abilities of bone marrow mesenchymal stem cell...For patients with osteoporosis,the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation,migration,and osteogenic differentiation abilities of bone marrow mesenchymal stem cells(BMSCs).展开更多
Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and sil...Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like reactions.Compared to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy barrier.Meanwhile,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues.The in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.展开更多
The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix(ECM)-mimicking biomaterials.However,designing control...The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix(ECM)-mimicking biomaterials.However,designing controllable multivalency construction strategies is still challenging.Herein,we synthesized a series of well-defined multivalent antimicrobial peptide polymers(mAMPs)by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer polymerization.The multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding,leading to amplification of the bactericidal effect.In addition to multivalency-enhanced antibacterial activity,mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic structure.The resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin wounds.The multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.展开更多
Eight intact LTR retrotransposons(Nbr1?Nbr8)have been previously characterized from the genome of Nosema bombycis,a eu-karyotic parasite with a compact and reduced genome.Here we describe six novel transcribed Nbr ele...Eight intact LTR retrotransposons(Nbr1?Nbr8)have been previously characterized from the genome of Nosema bombycis,a eu-karyotic parasite with a compact and reduced genome.Here we describe six novel transcribed Nbr elements(Nbr9?Nbr14)identified through either cDNA library or RT-PCR.Like previously determined ones,all of them belong to the Ty3/Gypsy superfamily.Retrotransposon diversity and incomplete domains with insertions(Nbr12),deletions(Nbr11)and in-frame stop codons in coding regions(Nbr9)were detected,suggesting that both defective and loss events of LTR retrotransposon have happened in N.bombycis genome.Analysis of selection showed that strong purifying selection acts on all elements except Nbr11.This implies that selective pressure keeps both these Nbrs and their functions in genome.Interestingly,Nbr11 is under positive selection and some positively selected codons were identified,indicating that new functionality might have evolved in the Nbr11 retrotransposon.Unlike other transposable elements,Nbr11 has integrated into a conserved syntenic block and probably resulted in the inversion of both flanking regions.This demonstrates that transposable element is an important factor for the reshuffling and evolution of their host genomes,and may be maintained under natural selection.展开更多
Polyetheretherketone(PEEK)has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance.However,its biological inertness,poor osteoinduction,and weak antibacterial a...Polyetheretherketone(PEEK)has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance.However,its biological inertness,poor osteoinduction,and weak antibacterial activity make the clinical applications in a dilemma.Inspired by the mussel adhesion mechanism,here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins(Mfps)-mimic peptide with clickable azido terminal.The peptide enables mussel-like adhesion on PEEK biomaterial surfaces,leaving azido groups for the further steps of biofunctionalizations.In this study,antimicrobial peptide(AMP)and osteogenic growth peptide(OGP)were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair.Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios,an optimal PEEK surface was finally obtained in this research,which could long-term inhibit bacterial growth,stabilize bone homeostasis and facilitate interfacial bone regeneration.In a word,this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants,in particular,achieving rational integration of multiple biofunctions to match clinical requirements.展开更多
In this work,we present a versatile surface engineering strategy by the combination of mussel adhesive peptide mimicking and bioorthogonal click chemistry.The main idea reflected in this work derived from a novel muss...In this work,we present a versatile surface engineering strategy by the combination of mussel adhesive peptide mimicking and bioorthogonal click chemistry.The main idea reflected in this work derived from a novel mussel-inspired peptide mimic with a bioclickable azide group(i.e.,DOPA_(4)-azide).Similar to the adhesion mechanism of the mussel foot protein(i.e.,covalent/noncovalent comediated surface adhesion),the bioinspired and bioclickable peptide mimic DOPA_(4)-azide enables stable binding on a broad range of materials,such as metallic,inorganic,and organic polymer substrates.In addition to the material universality,the azide residues of DOPA_(4)-azide are also capable of a specific conjugation of dibenzylcyclooctyne-(DBCO-)modified bioactive ligands through bioorthogonal click reaction in a second step.To demonstrate the applicability of this strategy for diversified biofunctionalization,we bioorthogonally conjugated several typical bioactive molecules with DBCO functionalization on different substrates to fabricate functional surfaces which fulfil essential requirements of biomedically used implants.For instance,antibiofouling,antibacterial,and antithrombogenic properties could be easily applied to the relevant biomaterial surfaces,by grafting antifouling polymer,antibacterial peptide,and NO-generating catalyst,respectively.Overall,the novel surface bioengineering strategy has shown broad applicability for both the types of substrate materials and the expected biofunctionalities.Conceivably,the“clean”molecular modification of bioorthogonal chemistry and the universality of mussel-inspired surface adhesion may synergically provide a versatile surface bioengineering strategy for a wide range of biomedical materials.展开更多
In this work,a sialic acid(SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells.The SA-imprinting process was performed at 37℃ using thermo-responsive function...In this work,a sialic acid(SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells.The SA-imprinting process was performed at 37℃ using thermo-responsive functional monomer,thus generating switchable SA-recognition sites with potent SA binding at 37℃and weak binding at a lower temperature(e.g.,25℃).Since SA is often overexpressed at the glycan terminals of cell membrane proteins or lipids,the SA-imprinted hydrogel layer could be used for selective cancer cell recognition.Our results confirmed that the hydrogel layer could efficiently capture cancer cells from not only the culture medium but also the real blood samples.In addition,the captured cells could be non-invasively released by lowing the temperature.Considering the non-invasive processing mode,considerable capture efficiency,good cell selectivity,as well as the more stable and durable SA-imprinted sites compared to natural antibodies or receptors,this thermo-responsive hydrogel layer could be used as a promising and general platform for cell-based cancer diagnosis.展开更多
Simulation of self-recovery and diversity of natural photonic crystal(PC)structures remain great challenges for artificial PC materials.Motivated by the dynamic characteristics of PC nanostructures,here,we present a n...Simulation of self-recovery and diversity of natural photonic crystal(PC)structures remain great challenges for artificial PC materials.Motivated by the dynamic characteristics of PC nanostructures,here,we present a new strategy for the design of hydrogel-based artificial PC materials with reversible interactions in the periodic nanostructures.The dynamic PC hydrogels,derived from self-assembled microgel colloidal crystals,were tactfully constructed by reversible crosslinking of adjacent microgels in the ordered structure via phenylboronate covalent chemistry.As proof of concept,three types of dynamic colloidal PC hydrogels with different structural colors were prepared.All the hydrogels showed perfect self-healing ability against physical damage.Moreover,dynamic crosslinking within the microgel crystals enabled shear-thinning injection of the PC hydrogels through a syringe(indicating injectability or printability),followed by rapid recovery of the structural colors.In short,in addition to the great significance in biomimicry of self-healing function of natural PC materials,our work provides a facile strategy for the construction of diversified artificial PC materials for different applications such as chem-/biosensing,counterfeit prevention,optical display,and energy conversion.展开更多
Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to...Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to prosthesis loosening,bone collapse,and implant failure.In this study,we firstly designed clickable mussel-inspired peptides(DOPA-N3)and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions.Then,two dibenzylcyclooctyne(DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain(BMP-2)were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction.We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1.In vitro,the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells(MSCs),and conspicuous immunopolarization-regulation to shift macrophages to alternative(M2)phenotypes and inhibit inflammation,as well as enhancement of osseointegration and mechanical stability in osteoporotic rats.In summary,our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants,which was conducive to the long-term success of Ti implants,especially in the osteoporotic or inflammatory conditions.展开更多
In the article titled,“A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic”[1],there was an error in Figure 2.In panel(e),the cell pictures of PEG after culture for 24...In the article titled,“A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic”[1],there was an error in Figure 2.In panel(e),the cell pictures of PEG after culture for 24 and 72 h were updated.The corrected figure is shown and is listed as Figure 1.展开更多
文摘目的研究受体酪氨酸激酶样孤儿受体1(receptor tyrosine kinase-like orphan rectetpor 1,ROR1)在不同病理亚型肺腺癌组织中的表达与气腔播散(spread through air space,STAS)发生的关系。方法收集昆明医科大学第一附属医院病理科2017年6月至2022年1月,肺腺癌组织蜡块标本618例,采用HE染色切片判断病理亚型与病理特征,记数STAS数量并分级,免疫组化染色,半定量判读ROR1表达水平,统计分析ROR1表达与STAS数量及与病理亚型的关系。结果ROR1在微乳头型与实体型肺腺癌(低分化)中的表达高于其它亚型肺腺癌,差异有统计学意义(P<0.001);ROR1在低STAS、高STAS组中表达率分别为88.0%、94.1%,高于无STAS组且差异有统计学意义(P<0.001)。结论ROR1高表达于低分化肺腺癌并提示更高的STAS发生率。ROR1有望成为新的肺腺癌诊断生物标志物用于指导临床治疗及辅助预后判断,并可能成为STAS阳性肺腺癌的潜在治疗靶点。
基金Supported by the Policy Guidance Plan of Jiangsu Province(Production and Research Cooperation)(BY2016061-27)College Students’Practice Innovation Training Program of Jiangsu Province(201811049045X)
文摘With the leaves,bark and roots of Liriodendron chinense Sarg.× L.tulipifera L.as experiment materials,the ultrasonic-assisted extraction conditions of total flavonoids were optimized by response surface Box-Behnken test design.Ultrasonic time and liquid-to-solid ratio had significant effects on the extraction amount of flavonoids from the leaves of L.chinense Sarg.× L.tulipifera L.;ultrasonic temperature and liquid-to-solid ratio had an interaction on the extraction amount of flavonoids;and the optimum ultrasonic time,temperature and liquid-to-solid ratio for the extraction of flavonoids from leaves of L.chinense Sarg.× L.tulipifera L.were 19.82 min,28.60 ℃ and 9.48 ml/g,respectively.Ultrasonic time,temperature and liquid-to-solid ratio had significant effects on the extraction amount of flavonoids from L.chinense Sarg.× L.tulipifera L.;there was a significant interaction between any two of the factors,which had a significant effect on the extraction of flavonoids;and the optimum extraction parameters for flavonoids in the bark were the ultrasonic time of 33.66 min,the ultrasonic temperature at 32.85 ℃ and the liquid-to-solid ratio of 11.39 ml/g.Ultrasonic time and liquid-to-solid ratio had significant effects on the extraction of flavonoids from roots;there was a significant interaction between ultrasonic time and liquid-to-solid ratio and between ultrasonic temperature and liquid-to-solid ratio;and the optimum extraction parameters for flavonoids from the roots of L.chinense Sarg.× L.tulipifera L.were the ultrasonic time of 32.38 min,the ultrasonic temperature at 25.0 ℃ and the liquid-to-solid ratio of 8.00 ml/g.The results of the three models were stable.The models are feasible and have good application value.
文摘With continuously increasing of photovoltaic (PV) plant’s penetration, it has become a critical issue to improve the fault ride-through capability of PV plant. This paper refers to the German grid code, and the PV system is controlled to keep grid connected, as well as inject reactive current to grid when fault occurs. The mathematical model of PV system is established and the fault characteristic is studied with respect to the control strategy. By analyzing the effect of reactive power supplied by the PV system to the point of common coupling (PCC) voltage, this paper proposes an adaptive voltage support control strategy to enhance the fault ride-through capability of PV system. The control strategy fully utilizes the PV system’s capability of voltage support and takes the safety of equipment into account as well. At last, the proposed control strategy is verified by simulation.
基金supported by the Project of Chongqing Science and Technology Commission(CSTC,2006AA5019)National Basic Research Program of China under the grant No.2005CB121000
文摘Microsporidia are a group of intracelluar eukaryotic parasites,which can infected almost all animals,including human beings.Till now,no mitochodria but mitosome,a remnant of mitochondria was discovered in this phylum.We present here the mitochondrial pyruvate dehydrogenase E1(PDH,including PDHα and PDHβ)of the microsporidian Nosema bombycis,the pathogen of silkworm pébrine.Compared with PDH of microsporidian Encephalitozoon cuniculi and Antonospora locustae,both subunits are conserved.The phylogeny indicated that both subunits are mitochondrial.The syntenic maps revealed the subunits organization of NbPDH is distributed in different scaffolds,similar to that of EcPDH but different with AlPDH,and the relationship between phylogeny tree and organization of PDH suggest that the AlPDH subunits organization is the ancestral style of microsporidia,and through the genome evolution,the reshuffling of the chromosome of microsporidia occurred,the adjacent style of ALPDHE1 organization changed,and the two subunits separated and located to different chromosomes in E.cuniculi.For N.bombycis and N.ceranae,they locate to different scaffolds.In order to determine NbPDH subcellular localizations,we prepared the polyclonal antibodies against NbPDH prokaryotic fusion proteins,and adopted the colloidal gold immunological electron microscopy,the expression signals of NbPDH were observed in spores however,the subcellular localization were not definited.In general,through comparison of three microsporidian PDH molecular phylogeny,subunits organization in chromosomes,localization indicated that PDH is an interesting marker in microsporidia evolution.
基金the National Natural Science Foundation of China(32222041,82102619,81925027,21875092)the Natural Science Foundation of Jiangsu Province(BK20220059)the National Key Research and Development Program of China(2019YFA0112000)。
文摘Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.
基金supported by the National Natural Science Foundation of China(82072425,82072498,81871788,21875092,31922040,82272157)the Natural Science Foundation of Jiangsu Province(BK2021650 and BK20220059)+5 种基金the“Jiangsu Specially-Appointed Professor”Programthe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Jiangsu Medical Research Project(ZD2022021)Special Project of DiagnosisTreatment Technology for Key Clinical Diseases in Suzhou(LCZX202003)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3217).
文摘Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction.Conventional approaches can regulate bone homeostasis to a certain extent.However,these therapies are still associated with some undesirable problems.Fortunately,recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related diseases.This review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related diseases.First,the potential utility of nanomaterials for biological imaging and biomarker detection is illustrated.Second,nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are highlighted.Finally,perspectives in this field are offered,including current key bottlenecks and future directions,which may be helpful for exploiting nanomaterials with novel properties and unique functions.This review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases.
基金This review work was supported by the National Natural Science Foundation of China(32222041,82072425,82072498,and 21875092)the Natural Science Foundation of Jiangsu Province(BK20220059 and BE2020666)+2 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(LCZX202003)the“jiangsu Specially Appointed Professor”Program and Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3217).
文摘For patients with osteoporosis,the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation,migration,and osteogenic differentiation abilities of bone marrow mesenchymal stem cells(BMSCs).
基金the National Natural Science Foundation of China(32222041,82072425,82160421,and 82072498)the Natural Science Foundation of Jiangsu Province(BE2020666,BK20211322,and BK20220059)+3 种基金Finland-China Food and Health International Pilot Project funded by the Finnish Ministry of Education and Culture,the Academy Research Fellow(328933)Solutions for Health Strategic Research Profiling Area(336355)InFLAMES Flagship(337531)Grants from Academy of Finland,the Special Project of Diagnosis and Treatment for Clinical Diseases of Suzhou(LCZX202003)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),and the jiangsu Specially Appointed Professor"Program and Postgraduate Research&Practice Innovation Program of jiangsu Province(KYCX22_3217).
文摘Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like reactions.Compared to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy barrier.Meanwhile,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues.The in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.
基金We acknowledge the National Natural Science Foundation of China(32222041,21875092 and 82272157)National Natural Science Foundation of Jiangsu Province(BK20220059)+1 种基金National Key Research and Development Program of China(2019YFA0112000)Innovation and Entrepreneurship Program of Jiangsu Province,and the“Jiangsu Specially-Appointed Professor”Program.
文摘The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix(ECM)-mimicking biomaterials.However,designing controllable multivalency construction strategies is still challenging.Herein,we synthesized a series of well-defined multivalent antimicrobial peptide polymers(mAMPs)by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer polymerization.The multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding,leading to amplification of the bactericidal effect.In addition to multivalency-enhanced antibacterial activity,mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic structure.The resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin wounds.The multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.
基金supported by the National Basic Research Program of China(No.2005CB121000)the project of Chongqing Science & Technology Commission(CSTC,No.2006AA5019 and 2009BB1241)+1 种基金the Programme of Introducing Talents of Discipline to Universities(No.B07045)State Development Fund at Risk of Callus Silk(No.M012005-000Y-00070)
文摘Eight intact LTR retrotransposons(Nbr1?Nbr8)have been previously characterized from the genome of Nosema bombycis,a eu-karyotic parasite with a compact and reduced genome.Here we describe six novel transcribed Nbr elements(Nbr9?Nbr14)identified through either cDNA library or RT-PCR.Like previously determined ones,all of them belong to the Ty3/Gypsy superfamily.Retrotransposon diversity and incomplete domains with insertions(Nbr12),deletions(Nbr11)and in-frame stop codons in coding regions(Nbr9)were detected,suggesting that both defective and loss events of LTR retrotransposon have happened in N.bombycis genome.Analysis of selection showed that strong purifying selection acts on all elements except Nbr11.This implies that selective pressure keeps both these Nbrs and their functions in genome.Interestingly,Nbr11 is under positive selection and some positively selected codons were identified,indicating that new functionality might have evolved in the Nbr11 retrotransposon.Unlike other transposable elements,Nbr11 has integrated into a conserved syntenic block and probably resulted in the inversion of both flanking regions.This demonstrates that transposable element is an important factor for the reshuffling and evolution of their host genomes,and may be maintained under natural selection.
基金supported by the National Key Research and Development Program of China(2019YFA0112000)Research and Development of Biomedical Materials and Substitution of Tissue and Organ Repair under the National Key R&D Program(2016YFC1101505)+7 种基金the National Natural Science Foundation of China(82072425,82072498,81873991,81073990,21875092,31922040 and 81672238)the Young Medical Talents of Jiangsu Province(QNRC2016751)the Natural Science Foundation of Jiangsu Province(BK20180001)the Innovation and Entrepreneurship Program of Jiangsu Provincethe“Six Talent Peaks”program of Jiangsu Province(2018-XCL-013)the Basic Applied Research Program of Suzhou City(SYS2018032,KJXW2017009)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Special Project of Diagnosis and Treatment for Clinical Diseases of Suzhou(LCZX202003).
文摘Polyetheretherketone(PEEK)has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance.However,its biological inertness,poor osteoinduction,and weak antibacterial activity make the clinical applications in a dilemma.Inspired by the mussel adhesion mechanism,here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins(Mfps)-mimic peptide with clickable azido terminal.The peptide enables mussel-like adhesion on PEEK biomaterial surfaces,leaving azido groups for the further steps of biofunctionalizations.In this study,antimicrobial peptide(AMP)and osteogenic growth peptide(OGP)were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair.Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios,an optimal PEEK surface was finally obtained in this research,which could long-term inhibit bacterial growth,stabilize bone homeostasis and facilitate interfacial bone regeneration.In a word,this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants,in particular,achieving rational integration of multiple biofunctions to match clinical requirements.
基金This work was supported by the National Key Research and Development Program of China(2019YFA0112000 and 2017YFB0702504)the National Natural Science Foundation of China(31570957 and 21875092)+2 种基金the International Cooperation Project by Science and Technology Department of Sichuan Province(2019YFH0103)the Applied Basic Research Project funded by Science and Technology Department of Sichuan Province(2017JY0296)the Innovation and Entrepreneurship Program of Jiangsu Province,and the Six Talent Peaks Project in Jiangsu Province(2018-XCL-013).
文摘In this work,we present a versatile surface engineering strategy by the combination of mussel adhesive peptide mimicking and bioorthogonal click chemistry.The main idea reflected in this work derived from a novel mussel-inspired peptide mimic with a bioclickable azide group(i.e.,DOPA_(4)-azide).Similar to the adhesion mechanism of the mussel foot protein(i.e.,covalent/noncovalent comediated surface adhesion),the bioinspired and bioclickable peptide mimic DOPA_(4)-azide enables stable binding on a broad range of materials,such as metallic,inorganic,and organic polymer substrates.In addition to the material universality,the azide residues of DOPA_(4)-azide are also capable of a specific conjugation of dibenzylcyclooctyne-(DBCO-)modified bioactive ligands through bioorthogonal click reaction in a second step.To demonstrate the applicability of this strategy for diversified biofunctionalization,we bioorthogonally conjugated several typical bioactive molecules with DBCO functionalization on different substrates to fabricate functional surfaces which fulfil essential requirements of biomedically used implants.For instance,antibiofouling,antibacterial,and antithrombogenic properties could be easily applied to the relevant biomaterial surfaces,by grafting antifouling polymer,antibacterial peptide,and NO-generating catalyst,respectively.Overall,the novel surface bioengineering strategy has shown broad applicability for both the types of substrate materials and the expected biofunctionalities.Conceivably,the“clean”molecular modification of bioorthogonal chemistry and the universality of mussel-inspired surface adhesion may synergically provide a versatile surface bioengineering strategy for a wide range of biomedical materials.
基金supported by the National Key Research and Development Program of China(2019YFA0112000 and 2016YFC1100203)the National Natural Science Foundation of China(21875092,81925027,21706099 and 81471790)+2 种基金the China Postdoctoral Science Foundation(2016M601745)the Innovation and Entrepreneurship Program of Jiangsu Province,the“Six Talent Peaks”program of Jiangsu Province(2018-XCL-013)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘In this work,a sialic acid(SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells.The SA-imprinting process was performed at 37℃ using thermo-responsive functional monomer,thus generating switchable SA-recognition sites with potent SA binding at 37℃and weak binding at a lower temperature(e.g.,25℃).Since SA is often overexpressed at the glycan terminals of cell membrane proteins or lipids,the SA-imprinted hydrogel layer could be used for selective cancer cell recognition.Our results confirmed that the hydrogel layer could efficiently capture cancer cells from not only the culture medium but also the real blood samples.In addition,the captured cells could be non-invasively released by lowing the temperature.Considering the non-invasive processing mode,considerable capture efficiency,good cell selectivity,as well as the more stable and durable SA-imprinted sites compared to natural antibodies or receptors,this thermo-responsive hydrogel layer could be used as a promising and general platform for cell-based cancer diagnosis.
基金support from the National Key Research and Development Program of China(2019YFA0112000)the National Natural Science Foundation of China(21875092,21706099,and 91649204)+5 种基金the start-up fund(1-ZE7S)central research fund(G-YBWS)from the Hong Kong Polytechnic University,the China Postdoctoral Science Foundation funded project(2018M642174)the Postdoctoral Science Foundation of Jiangsu Province(2019K145)the Natural Science Foundation of Jiangsu Province(BK20160056 and BK20160491)the Innovation and Entrepreneurship Program of Jiangsu Provincethe Six Talent Peaks Project in Jiangsu Province(2018-XCL-013).
文摘Simulation of self-recovery and diversity of natural photonic crystal(PC)structures remain great challenges for artificial PC materials.Motivated by the dynamic characteristics of PC nanostructures,here,we present a new strategy for the design of hydrogel-based artificial PC materials with reversible interactions in the periodic nanostructures.The dynamic PC hydrogels,derived from self-assembled microgel colloidal crystals,were tactfully constructed by reversible crosslinking of adjacent microgels in the ordered structure via phenylboronate covalent chemistry.As proof of concept,three types of dynamic colloidal PC hydrogels with different structural colors were prepared.All the hydrogels showed perfect self-healing ability against physical damage.Moreover,dynamic crosslinking within the microgel crystals enabled shear-thinning injection of the PC hydrogels through a syringe(indicating injectability or printability),followed by rapid recovery of the structural colors.In short,in addition to the great significance in biomimicry of self-healing function of natural PC materials,our work provides a facile strategy for the construction of diversified artificial PC materials for different applications such as chem-/biosensing,counterfeit prevention,optical display,and energy conversion.
基金This work was supported by the National Key Research and Development Program of China(2019YFA0112000)the National Natural Science Foundation of China(81972059,81772358,21875092)+1 种基金the key R&D programs of Jiangsu Province(BE2019668),China Postdoctoral Science Foundation(2020M671587)Jiangsu Provincial Clinical Orthopedic Center,Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the High-level Talents Research and Development Program of Affiliated Dongguan Hospital,Southern Medical University(K202102).
文摘Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to prosthesis loosening,bone collapse,and implant failure.In this study,we firstly designed clickable mussel-inspired peptides(DOPA-N3)and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions.Then,two dibenzylcyclooctyne(DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain(BMP-2)were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction.We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1.In vitro,the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells(MSCs),and conspicuous immunopolarization-regulation to shift macrophages to alternative(M2)phenotypes and inhibit inflammation,as well as enhancement of osseointegration and mechanical stability in osteoporotic rats.In summary,our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants,which was conducive to the long-term success of Ti implants,especially in the osteoporotic or inflammatory conditions.
文摘In the article titled,“A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic”[1],there was an error in Figure 2.In panel(e),the cell pictures of PEG after culture for 24 and 72 h were updated.The corrected figure is shown and is listed as Figure 1.
