Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic m...Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.展开更多
Sulfydryl-contained(-SH)substances including hydrogen sulfide(H_(2)S),cysteine(Cys),homocysteine(Hcy)and glutathione(GSH)play crucial roles in living systems,and their variations are closely associated with various di...Sulfydryl-contained(-SH)substances including hydrogen sulfide(H_(2)S),cysteine(Cys),homocysteine(Hcy)and glutathione(GSH)play crucial roles in living systems,and their variations are closely associated with various diseases.Herein,we developed a near-infrared intramolecular charge transfer(ICT)based fluorescent probe Y-NBD,achieving detection of Cys/Hcy and H_(2)S with different fluorescent signals(green-red for Cys/Hcy,red for H_(2)S),large Stokes shifts(∼100/105nm or 191 nm)and high signal-background-ratio,but not responding to GSH.Y-NBD was successfully applied to image exogenous/endogenous Cys/Hcy and H_(2)S in various living cancer cells(HeLa,A549,and HepG2)and in zebrafish.It not only visualized the transformation pathway of several thiols in HepG2 cells but also verified that the intestine is the main site for the activation and metabolism of Y-NBD in zebrafish,as well as realized to evaluate the degree of drug-induced liver injury.This work provides a promising tool for imaging Cys/Hcy and H_(2)S in living systems and shows great potency in evaluating drug-induced liver injury and its treatment.展开更多
Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent pr...Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.展开更多
The widespread applications of aggregation-induced emission luminogens(AIEgens)inspire the creation of AIEgens with novel structures and functionalities.In this work,we focused on the direct and efficient synthesis of...The widespread applications of aggregation-induced emission luminogens(AIEgens)inspire the creation of AIEgens with novel structures and functionalities.In this work,we focused on the direct and efficient synthesis of a new type of AIEgens,imidazo[1,5-a]pyridicne derivatives,via iodine mediated cascade oxidative Csp^(2)–H or Csp–H amination route from phenylacetylene or styrenes under mild conditions.The resulted compounds showed excellent AIE characteristics with tunable maximum emissions,attractive bioimaging performance,and potential anti-inflammatory activity,which exert broad application prospects in material,biology,medicine,and other relevant areas.展开更多
Dual-state emission(DSE)molecules displayed conspicuous fluorescent performance both in solid and solution states.However,the construction of DSE molecules and the regulation of their emission wavelengths remains a gr...Dual-state emission(DSE)molecules displayed conspicuous fluorescent performance both in solid and solution states.However,the construction of DSE molecules and the regulation of their emission wavelengths remains a great challenge.Based on the structure-function relationship of quinolinonitrile-type fluorophores,this work proposed a feasible strategy for modulating their fluorescent properties into DSE via limiting the torsion angle between the quinoline ring and C=C bond in the range of 4.7°to 30°.Based on this strategy,53 compounds were obtained which displayed tunable emission wavelengths from^(3)97 nm to 740 nm in solid-state and from 360 nm to 672 nm in solution.The feasibility of the strategy was supported by a series of theoretical calculations,optical characterizations,and crystal analysis,suggesting the compounds have great potential in imaging living cells and tissues with desired wavelengths.展开更多
A close relationship has been reported to exist between cadherin-mediated cell-cell adhesion and integrin-mediated cell mobility,and protein tyrosine phosphatase 1B(PTP1B)may be involved in maintaining this homeostasi...A close relationship has been reported to exist between cadherin-mediated cell-cell adhesion and integrin-mediated cell mobility,and protein tyrosine phosphatase 1B(PTP1B)may be involved in maintaining this homeostasis.The stable residence of mesenchymal stem cells(MSCs)and endothelial cells(ECs)in their niches is closely related to the regulation of PTP1B.However,the exact role of the departure of MSCs and ECs from their niches during bone regeneration is largely unknown.Here,we show that the phosphorylation state of PTP1B tyrosine-152(Y152)plays a central role in initiating the departure of these cells from their niches and their subsequent recruitment to bone defects.Based on our previous design of a PTP1B Y152 region-mimicking peptide(152RM)that significantly inhibits the phosphorylation of PTP1B Y152,further investigations revealed that 152RM enhanced cell migration partly via integrinαvβ3 and promoted MSCs osteogenic differentiation partly by inhibiting ATF3.Moreover,152RM induced type H vessels formation by activating Notch signaling.Demineralized bone matrix(DBM)scaffolds were fabricated with mesoporous silica nanoparticles(MSNs),and 152RM was then loaded onto them by electrostatic adsorption.The DBM-MSN/152RM scaffolds were demonstrated to induce bone formation and type H vessels expansion in vivo.In conclusion,our data reveal that 152RM contributes to bone formation by coupling osteogenesis with angiogenesis,which may offer a potential therapeutic strategy for bone defects.展开更多
Background:Dermatofibrosarcoma protuberans(DFSP)is an uncommon cutaneous sarcoma that infrequently involves the head and face.Despite its low incidence,the complex anatomical subunits of this region and frequent misdi...Background:Dermatofibrosarcoma protuberans(DFSP)is an uncommon cutaneous sarcoma that infrequently involves the head and face.Despite its low incidence,the complex anatomical subunits of this region and frequent misdiagnosis can result in functional impairment and challenging reconstruction.However,the distribution characteristics of DFSP in the head and face have not yet been systematically evaluated.This study aimed to characterize the distribution of DFSP in the head and face to provide guidance for clinical diagnosis.Methods:We retrospectively reviewed patients who underwent treatment for DFSP involving the head and face at our hospital.The associations between tumor location and patient characteristics—including sex,age,tumor size,history of trauma,and histopathological features—were systematically analyzed.Results:Among the 161 cases,26(16.1%)involved DFSP of the head and face.The highest tumor frequency was observed in the cheek region(65.38%).Patients with DFSP located in the cheek were older than those with DFSP in non-cheek regions(48.82 vs.37.22 years,P=0.04).Histologically,among the 26 cases,23 were classic DFSP and 3 were fibrosarcomatous dermatofibrosarcoma protuberans(FS-DFSP),a more aggressive histologic subtype.The proportion of FS-DFSP was lower in the cheek region than in non-cheek areas(0 vs.3,P=0.032).Conclusion:DFSP of the head and face demonstrated a predilection for the cheek region.Recognition of this distribution pattern may assist dermatologists in the clinical assessment and management of patients,particularly for lesions involving the cheeks.展开更多
Thiophenol(PhSH)is an important raw material for organic synthesis,while its high toxicity to organisms makes it an environmental pollutant.Therefore,it is crucial to accurately detect PhSH and explore its metabolic p...Thiophenol(PhSH)is an important raw material for organic synthesis,while its high toxicity to organisms makes it an environmental pollutant.Therefore,it is crucial to accurately detect PhSH and explore its metabolic process in the living system.Herein,a near-infrared(NIR)fluorescent probe TEM-FB was developed for sensing PhSH with a turn-on fluorescent signal at 719nm and a large Stokes shift(198 nm)based on generating the intramolecular charge transfer(ICT)process.TEM-FB shows high specificity and significant sensitivity towards PhSH(detection limit:10 nmol/L)via the aromatic nucleophilic substitution mechanism.Furthermore,it was successfully applied to image PhSH in multiple cell lines and in zebrafish.Notably,we revealed the oxidative stress process caused by PhSH and demonstrated that the hydrogen peroxide(H_(2)O_(2))in cells would alleviate the poisonousness from exogenous PhSH for the first time.This work provides a promising bioimaging tool for monitoring PhSH in living systems and visualizing the process of oxidative stress induced by PhSH.展开更多
Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction.The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regenerati...Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction.The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regeneration remains a great challenge in regenerative medicine.Here,we present a reliable method to rapidly fabricate tissueengineered tubular scaffold with hierarchical structure via 4-axis printing system.The fabrication process can be adapted to various biomaterials including hydrogels,thermoplastic materials and thermosetting materials.Using polycaprolactone(PCL)as an example,we successfully fabricated the scaffolds with tunable tubular architecture,controllable mesh structure,radial elasticity,good flexibility,and luminal patency.As a preliminary demonstration of the applications of this technology,we prepared a hybrid tubular scaffold via the combination of the 4-axis printed elastic poly(glycerol sebacate)(PGS)bio-spring and electrospun gelatin nanofibers.The scaffolds seeded with chondrocytes formed tubular mature cartilage-like tissue both via in vitro culture and subcutaneous implantation in the nude mouse,which showed great potential for tracheal cartilage reconstruction.展开更多
Xenogeneic acellular dermal matrix(ADM)is widely used in clinical practice given its good biocompatibility and biomechanical properties.Yet,its dense structure remains a hindrance.Incorporation of laser drilling and p...Xenogeneic acellular dermal matrix(ADM)is widely used in clinical practice given its good biocompatibility and biomechanical properties.Yet,its dense structure remains a hindrance.Incorporation of laser drilling and pre-culture with Adipose-derived stem cells(ADSCs)have been attempted to promote early vascularization and integration,but the results were not ideal.Inspired by the manufacturing procedure of frozen bean curd,we proposed a freeze–thaw treatment to enhance the porosity of ADM.We found that the ADM treated with-80℃3Rt-30℃3R had the largest disorder of stratified plane arrangement(deviation angle 28.6%)and the largest porosity(96%),making it an optimal approach.Human umbilical vein endothelial cells on freeze–thaw treated ADM demonstrated increased expression in Tie-2 and CD105 genes,proliferation,and tube formation in vitro compared with those on ADM.Combining freeze–thaw with laser drilling and pre-culture with ADSCs,such tri-treatment improved the gene expression of proangiogenic factors including IGF-1,EGF and vascular endothelial growth factor,promoted tube formation,increased cell infiltration and accelerated vascularization soon after implantation.Overall,freeze–thaw is an effective method for optimizing the internal structure of ADM,and tri-treatments may yield clinical significance by promoting early cell infiltration,vascularization and integration with surrounding tissues.展开更多
Osteoarthritis(OA)is the most prevalent joint disease,yet effective disease-modifying OA drugs(DMOADs)remain elusive.Targeting macrophage polarization has emerged as a promising avenue for OA treatment.This study iden...Osteoarthritis(OA)is the most prevalent joint disease,yet effective disease-modifying OA drugs(DMOADs)remain elusive.Targeting macrophage polarization has emerged as a promising avenue for OA treatment.This study identified skatole through high-throughput screening as an efficient modulator of macrophage polarization.In vivo experiments demonstrated that skatole administration markedly reduced synovitis and cartilage damage in both destabilization of medial meniscus(DMM)-induced OA mice and monosodium iodoacetate(MIA)-induced OA rats.Mechanistically,skatole activated signal transducer and activator of transcription 6(Stat6)signaling,promoting M2 macrophage polarization,while inhibiting nuclear factor-κB(NFκB)and mitogen-activated protein kinase(MAPK)signaling pathways to suppress M1 polarization.RNA-sequencing analysis,targeted metabolomics,and mitochondrial stress tests further revealed that skatole treatment shifted macrophages toward oxidative phosphorylation for energy production.Additionally,it up-regulated genes associated with glutathione metabolism and reactive oxygen species(ROS)pathways,reducing intracellular ROS production.The CUT&Tag assay results indicated that the downstream transcription factor p65 of NFκB can directly bind to gene loci related to inflammation,oxidative phosphorylation,and glutathione metabolism,thereby modulating gene expression.This regulatory process is inhibited by skatole.At the chondrocyte level,conditional medium from skatole-treated M1 macrophages balanced anabolism and catabolism in mouse chondrocytes and inhibited apoptosis.In IL1β-treated chondrocytes,skatole suppressed inflammation and catabolism without affecting apoptosis or anabolism.Overall,skatole maintains immune microenvironment homeostasis by modulating macrophage polarization in joints and preserves cartilage function by balancing chondrocyte anabolism and catabolism,effectively alleviating OA.These findings suggest skatole’s potential as a DMOAD.展开更多
Tissue engineering provides a promising approach for regenerative medicine.The ideal engineered tissue should have the desired structure and functional properties suitable for uniform cell distribution and stable shap...Tissue engineering provides a promising approach for regenerative medicine.The ideal engineered tissue should have the desired structure and functional properties suitable for uniform cell distribution and stable shape fidelity in the full period of in vitro culture and in vivo implantation.However,due to insufficient cell infiltration and inadequate mechanical properties,engineered tissue made from porous scaffolds may have an inconsistent cellular composition and a poor shape retainability,which seriously hinders their further clinical application.In this study,silk fibroin was integrated with silk short fibers with a physical and chemical double-crosslinking network to fabricate fiber-reinforced silk fibroin super elastic absorbent sponges(Fr-SF-SEAs).The Fr-SF-SEAs exhibited the desirable synergistic properties of a honeycomb structure,hygroscopicity and elasticity,which allowed them to undergo an unconventional cyclic compression inoculation method to significantly promote cell diffusion and achieve a uniform cell distribution at a high-density.Furthermore,the regenerated cartilage of the Fr-SF-SEAs scaffold withstood a dynamic pressure environment after subcutaneous implantation and maintained its precise original structure,ultimately achieving human-scale ear-shaped cartilage regeneration.Importantly,the SF-SEAs prepara-tion showed valuable universality in combining chemicals with other bioactive materials or drugs with reactive groups to construct microenvironment bionic scaffolds.The established novel cell inoculation method is highly versatile and can be readily applied to various cells.Based on the design concept of dual-network Fr-SF-SEAs scaffolds,homogenous and mature cartilage was successfully regenerated with precise and complicated shapes,which hopefully provides a platform strategy for tissue engineering for various cartilage defect repairs.展开更多
The biomedical application of self-healing materials in wet or(under)water environments is quite challenging because the insulation and dissociation effects of water molecules significantly reduce the reconstruction o...The biomedical application of self-healing materials in wet or(under)water environments is quite challenging because the insulation and dissociation effects of water molecules significantly reduce the reconstruction of material–interface interactions.Rapid closure with uniform tension of high-tension wounds is often difficult,leading to further deterioration and scarring.Herein,a new type of thermosetting water-resistant self-healing bioelastomer(WRSHE)was designed by synergistically incorporating a stable polyglycerol sebacate(PGS)covalent crosslinking network and triple hybrid dynamic networks consisting of reversible disulfide metathesis(SS),and dimethylglyoxime urethane(Dou)and hydrogen bonds.And a resveratrol-loaded WRSHE(Res@WRSHE)was developed by a swelling,absorption,and crosslinked network locking strategy.WRSHEs exhibited skin-like mechanical properties in terms of nonlinear modulus behavior,biomimetic softness,high stretchability,and good elasticity,and they also achieved ultrafast and highly efficient self-healing in various liquid environments.For wound-healing applications of high-tension full-thickness skin defects,the convenient surface assembly by self-healing of WRSHEs provides uniform contraction stress to facilitate tight closure.Moreover,Res@WRSHEs gradually release resveratrol,which helps inflammatory response reduction,promotes blood vessel regeneration,and accelerates wound repair.展开更多
基金supported by the National Natural Science Foundation of China(No.82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)partially supported by Wuhan Kangchuang Biotechnology Co.,Ltd。
文摘Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.
基金supported by the National Natural Science Foundation of China(Nos.22077099 and 22171223)the Innovation Capability Support Program of Shaanxi(Nos.2023-CX-TD-75 and 2022KJXX-32)+4 种基金the Technology Innovation Leading Program of Shaanxi(Program No.2023KXJ-209)the Natural Science Basic Research Program of Shaanxi(Nos.2022JQ-151 and 2023-JC-YB-141)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(Nos.22JHZ010 and 22JHQ080)the Yan’an City Science and Technology Project(No.2022SLZDCY-002).
文摘Sulfydryl-contained(-SH)substances including hydrogen sulfide(H_(2)S),cysteine(Cys),homocysteine(Hcy)and glutathione(GSH)play crucial roles in living systems,and their variations are closely associated with various diseases.Herein,we developed a near-infrared intramolecular charge transfer(ICT)based fluorescent probe Y-NBD,achieving detection of Cys/Hcy and H_(2)S with different fluorescent signals(green-red for Cys/Hcy,red for H_(2)S),large Stokes shifts(∼100/105nm or 191 nm)and high signal-background-ratio,but not responding to GSH.Y-NBD was successfully applied to image exogenous/endogenous Cys/Hcy and H_(2)S in various living cancer cells(HeLa,A549,and HepG2)and in zebrafish.It not only visualized the transformation pathway of several thiols in HepG2 cells but also verified that the intestine is the main site for the activation and metabolism of Y-NBD in zebrafish,as well as realized to evaluate the degree of drug-induced liver injury.This work provides a promising tool for imaging Cys/Hcy and H_(2)S in living systems and shows great potency in evaluating drug-induced liver injury and its treatment.
基金supported by the National Natural Science Foundation of China(Nos.22077099,22171223 and 22307102)the Innovation Capability Support Program of Shaanxi(Nos.2023-CXTD-75 and 2022KJXX-32)+5 种基金the Technology Innovation Leading Program of Shaanxi(Nos.2023KXJ-209 and 2024QCY-KXJ-142)the Key Research and Development Program of Shaanxi(No.2024GHZDXM-22)the Natural Science Basic Research Program of Shaanxi(Nos.2023-JC-YB-141 and 2022JQ-151)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(Nos.22JHZ010 and 22JHQ080)the Yan’an City Science and Technology Project(No.2022SLZDCY-002)。
文摘Benzo[4,5]imidazo[1,2-a]pyrimidine-based derivatives play crucial roles in medicines,pesticides,tracers and photoelectric materials.However,their synthesis approach still needs to be optimized,and their fluorescent properties in intracellular microenvironment are unclear.Here,a Cu(II)-catalyzed cascade coupling cyclization reaction was successfully developed to synthesize benzo[4,5]imidazo[1,2-a]pyrimidine scaffold with mild reaction conditions,broad substrate scopes and high yields.After a system study,we found that compound 4aa displayed an optimal viscosity-specific response with remarkable fluorescence enhancement(102-fold)for glycerol at 490 nm.Particularly,4aa possessed excellent structure-inherent targeting(SIT)capability for lysosome(P=0.95)with high p H stability and large Stokes shift.Importantly,4aa was validated for its effectiveness in diagnosing lysosomal storage disorders(LSD)in living cells.The 4aa also showed its potential to map the micro-viscosity and its metabolism process in zebrafish.This work not only affords an efficient protocol to fabricate benzo[4,5]imidazo[1,2-a]pyrimidine derivatives,reveals this skeleton has excellent SIT features for lysosome,but also manifests that 4aa can serve as a practical tool to monitor lysosomal viscosity and diagnose LSD.
基金financially supported by the National Natural Science Foundation of China(Nos.22077099,21807087and 21673173)Key Research and Development Plan in Shaanxi Province of China(No.2019KWZ-07)+2 种基金the Technology Innovation Leading Program of Shaanxi(No.2020TG-031)the Xi’an CityScience and Technology Project(Nos.2019218214GXRC018CG019-GXYD18.4 and 2020KJRC0115)the support from COVID-19 Prophylaxis and Treatment Emergency Research Special Projects of Northwest University。
文摘The widespread applications of aggregation-induced emission luminogens(AIEgens)inspire the creation of AIEgens with novel structures and functionalities.In this work,we focused on the direct and efficient synthesis of a new type of AIEgens,imidazo[1,5-a]pyridicne derivatives,via iodine mediated cascade oxidative Csp^(2)–H or Csp–H amination route from phenylacetylene or styrenes under mild conditions.The resulted compounds showed excellent AIE characteristics with tunable maximum emissions,attractive bioimaging performance,and potential anti-inflammatory activity,which exert broad application prospects in material,biology,medicine,and other relevant areas.
基金supported by the National Natural Science Foundation of China(Nos.22077099 and 22171223)The Innovation Capability Support Program of Shaanxi(Nos.2023-CX-TD-75 and 2022KJXX-32)+5 种基金the Scientific and Technological Innovation Team of Shaanxi Province(No.2022TD-36)the Technology Innovation Leading Program of Shaanxi(No.2023KXJ-209)the Natural Science Basic Research Program of Shaanxi(Nos.2023-JC-YB-141 and 2022JQ-151)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(Nos.22JHZ010 and 22JHQ080)the Yan’an City Science and Technology Project(No.2022SLZDCY-002)。
文摘Dual-state emission(DSE)molecules displayed conspicuous fluorescent performance both in solid and solution states.However,the construction of DSE molecules and the regulation of their emission wavelengths remains a great challenge.Based on the structure-function relationship of quinolinonitrile-type fluorophores,this work proposed a feasible strategy for modulating their fluorescent properties into DSE via limiting the torsion angle between the quinoline ring and C=C bond in the range of 4.7°to 30°.Based on this strategy,53 compounds were obtained which displayed tunable emission wavelengths from^(3)97 nm to 740 nm in solid-state and from 360 nm to 672 nm in solution.The feasibility of the strategy was supported by a series of theoretical calculations,optical characterizations,and crystal analysis,suggesting the compounds have great potential in imaging living cells and tissues with desired wavelengths.
基金This work was supported by grants from the National Natural Science Foundation of China(81974336 and 82002308).
文摘A close relationship has been reported to exist between cadherin-mediated cell-cell adhesion and integrin-mediated cell mobility,and protein tyrosine phosphatase 1B(PTP1B)may be involved in maintaining this homeostasis.The stable residence of mesenchymal stem cells(MSCs)and endothelial cells(ECs)in their niches is closely related to the regulation of PTP1B.However,the exact role of the departure of MSCs and ECs from their niches during bone regeneration is largely unknown.Here,we show that the phosphorylation state of PTP1B tyrosine-152(Y152)plays a central role in initiating the departure of these cells from their niches and their subsequent recruitment to bone defects.Based on our previous design of a PTP1B Y152 region-mimicking peptide(152RM)that significantly inhibits the phosphorylation of PTP1B Y152,further investigations revealed that 152RM enhanced cell migration partly via integrinαvβ3 and promoted MSCs osteogenic differentiation partly by inhibiting ATF3.Moreover,152RM induced type H vessels formation by activating Notch signaling.Demineralized bone matrix(DBM)scaffolds were fabricated with mesoporous silica nanoparticles(MSNs),and 152RM was then loaded onto them by electrostatic adsorption.The DBM-MSN/152RM scaffolds were demonstrated to induce bone formation and type H vessels expansion in vivo.In conclusion,our data reveal that 152RM contributes to bone formation by coupling osteogenesis with angiogenesis,which may offer a potential therapeutic strategy for bone defects.
基金supported by grants from the National Natural Science Foundation of China (81871576, 82302836)the Shanghai Rising-Star Program (23YF1403700)the Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center (2023ZZ02023)
文摘Background:Dermatofibrosarcoma protuberans(DFSP)is an uncommon cutaneous sarcoma that infrequently involves the head and face.Despite its low incidence,the complex anatomical subunits of this region and frequent misdiagnosis can result in functional impairment and challenging reconstruction.However,the distribution characteristics of DFSP in the head and face have not yet been systematically evaluated.This study aimed to characterize the distribution of DFSP in the head and face to provide guidance for clinical diagnosis.Methods:We retrospectively reviewed patients who underwent treatment for DFSP involving the head and face at our hospital.The associations between tumor location and patient characteristics—including sex,age,tumor size,history of trauma,and histopathological features—were systematically analyzed.Results:Among the 161 cases,26(16.1%)involved DFSP of the head and face.The highest tumor frequency was observed in the cheek region(65.38%).Patients with DFSP located in the cheek were older than those with DFSP in non-cheek regions(48.82 vs.37.22 years,P=0.04).Histologically,among the 26 cases,23 were classic DFSP and 3 were fibrosarcomatous dermatofibrosarcoma protuberans(FS-DFSP),a more aggressive histologic subtype.The proportion of FS-DFSP was lower in the cheek region than in non-cheek areas(0 vs.3,P=0.032).Conclusion:DFSP of the head and face demonstrated a predilection for the cheek region.Recognition of this distribution pattern may assist dermatologists in the clinical assessment and management of patients,particularly for lesions involving the cheeks.
基金supported by the National Natural Science Foundation of China(Nos.22077099 and 22171223)the Technology Innovation Leading Program of Shaanxi(No.2020TG-031)+3 种基金the Innovation Capability Support Program of Shaanxi(Nos.2023-CXTD-75 and 2022KJXX-32)the Natural Science Basic Research Program of Shaanxi(No.2023-JC-YB-141)Young Talent Fund of Association for Science and Technology in Shaanxi,China(No.SWYY202206)the Natural Science Basic Research Plan in Shaanxi Province of China(Nos.2022JQ-151 and 2022JQ-125).
文摘Thiophenol(PhSH)is an important raw material for organic synthesis,while its high toxicity to organisms makes it an environmental pollutant.Therefore,it is crucial to accurately detect PhSH and explore its metabolic process in the living system.Herein,a near-infrared(NIR)fluorescent probe TEM-FB was developed for sensing PhSH with a turn-on fluorescent signal at 719nm and a large Stokes shift(198 nm)based on generating the intramolecular charge transfer(ICT)process.TEM-FB shows high specificity and significant sensitivity towards PhSH(detection limit:10 nmol/L)via the aromatic nucleophilic substitution mechanism.Furthermore,it was successfully applied to image PhSH in multiple cell lines and in zebrafish.Notably,we revealed the oxidative stress process caused by PhSH and demonstrated that the hydrogen peroxide(H_(2)O_(2))in cells would alleviate the poisonousness from exogenous PhSH for the first time.This work provides a promising bioimaging tool for monitoring PhSH in living systems and visualizing the process of oxidative stress induced by PhSH.
基金supported by the National Key Research and Development Program of China (2018YFB1105602 and 2017YFC1103900)the National Natural Science Foundation of China (21574019, 81320108010, 81571823 and 81871502)+4 种基金the Natural Science Foundation of Shanghai (18ZR1401900)the Fundamental Research Funds for the Central Universities, DHU Distinguished Young Professor Program (LZA2019001)the Science and Technology Commission of Shanghai (17DZ2260100 and 15DZ1941600)the Program for Shanghai Outstanding Medical Academic Leaderthe Program of Shanghai Technology Research Leader
文摘Long-segment defects remain a major problem in clinical treatment of tubular tissue reconstruction.The design of tubular scaffold with desired structure and functional properties suitable for tubular tissue regeneration remains a great challenge in regenerative medicine.Here,we present a reliable method to rapidly fabricate tissueengineered tubular scaffold with hierarchical structure via 4-axis printing system.The fabrication process can be adapted to various biomaterials including hydrogels,thermoplastic materials and thermosetting materials.Using polycaprolactone(PCL)as an example,we successfully fabricated the scaffolds with tunable tubular architecture,controllable mesh structure,radial elasticity,good flexibility,and luminal patency.As a preliminary demonstration of the applications of this technology,we prepared a hybrid tubular scaffold via the combination of the 4-axis printed elastic poly(glycerol sebacate)(PGS)bio-spring and electrospun gelatin nanofibers.The scaffolds seeded with chondrocytes formed tubular mature cartilage-like tissue both via in vitro culture and subcutaneous implantation in the nude mouse,which showed great potential for tracheal cartilage reconstruction.
基金supported by the Shanghai Committee of Science and Technology,China(grant no.19ZR1430100)National Natural Science Foundation of China(grant no.81371701)the Shanghai Municipal Key Clinical Specialty,China(grant no.shslczdzk00901).
文摘Xenogeneic acellular dermal matrix(ADM)is widely used in clinical practice given its good biocompatibility and biomechanical properties.Yet,its dense structure remains a hindrance.Incorporation of laser drilling and pre-culture with Adipose-derived stem cells(ADSCs)have been attempted to promote early vascularization and integration,but the results were not ideal.Inspired by the manufacturing procedure of frozen bean curd,we proposed a freeze–thaw treatment to enhance the porosity of ADM.We found that the ADM treated with-80℃3Rt-30℃3R had the largest disorder of stratified plane arrangement(deviation angle 28.6%)and the largest porosity(96%),making it an optimal approach.Human umbilical vein endothelial cells on freeze–thaw treated ADM demonstrated increased expression in Tie-2 and CD105 genes,proliferation,and tube formation in vitro compared with those on ADM.Combining freeze–thaw with laser drilling and pre-culture with ADSCs,such tri-treatment improved the gene expression of proangiogenic factors including IGF-1,EGF and vascular endothelial growth factor,promoted tube formation,increased cell infiltration and accelerated vascularization soon after implantation.Overall,freeze–thaw is an effective method for optimizing the internal structure of ADM,and tri-treatments may yield clinical significance by promoting early cell infiltration,vascularization and integration with surrounding tissues.
基金supported by the National Natural Science Foundation of China(32200754)the Henan Provincial Science and Technology Research and Development Joint Fund(Industrial)(235101610001)+3 种基金the Key Research and Development Program of Henan Province(221111310100)the Key Research and Development and Promotion Special(Science and Technology)Project of Henan Province(242102310321,242102230124)the Open Research Fund of Tissue Engineering and Regenerative Clinical Medical Center of Xinxiang Medical University(2022YFYKFKT05,2022KFKTZD03)the Natural Science Foundation of Henan Province(232300421314).
文摘Osteoarthritis(OA)is the most prevalent joint disease,yet effective disease-modifying OA drugs(DMOADs)remain elusive.Targeting macrophage polarization has emerged as a promising avenue for OA treatment.This study identified skatole through high-throughput screening as an efficient modulator of macrophage polarization.In vivo experiments demonstrated that skatole administration markedly reduced synovitis and cartilage damage in both destabilization of medial meniscus(DMM)-induced OA mice and monosodium iodoacetate(MIA)-induced OA rats.Mechanistically,skatole activated signal transducer and activator of transcription 6(Stat6)signaling,promoting M2 macrophage polarization,while inhibiting nuclear factor-κB(NFκB)and mitogen-activated protein kinase(MAPK)signaling pathways to suppress M1 polarization.RNA-sequencing analysis,targeted metabolomics,and mitochondrial stress tests further revealed that skatole treatment shifted macrophages toward oxidative phosphorylation for energy production.Additionally,it up-regulated genes associated with glutathione metabolism and reactive oxygen species(ROS)pathways,reducing intracellular ROS production.The CUT&Tag assay results indicated that the downstream transcription factor p65 of NFκB can directly bind to gene loci related to inflammation,oxidative phosphorylation,and glutathione metabolism,thereby modulating gene expression.This regulatory process is inhibited by skatole.At the chondrocyte level,conditional medium from skatole-treated M1 macrophages balanced anabolism and catabolism in mouse chondrocytes and inhibited apoptosis.In IL1β-treated chondrocytes,skatole suppressed inflammation and catabolism without affecting apoptosis or anabolism.Overall,skatole maintains immune microenvironment homeostasis by modulating macrophage polarization in joints and preserves cartilage function by balancing chondrocyte anabolism and catabolism,effectively alleviating OA.These findings suggest skatole’s potential as a DMOAD.
基金support from the National Key Research and Development Program of China(2018YFC1105800,2017YFC1103900)the National Natural Science Foundation of China(82102211,81871502)+5 种基金the Shanghai Municipal Key Clinical Specialty(shslczdzk06601)the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)the Key Research and Development Program of Henan Province(No.221111310100)the Major Science and Technology Projects of Xinxiang City(No.21ZD006)the Clinical Research Plan of SHDC(No.SHDC2020CR2045B)the Start-up Funds of Talent Construction and Scientific Research in Shanghai 9th People's Hospital(2021rcyj-ld).
文摘Tissue engineering provides a promising approach for regenerative medicine.The ideal engineered tissue should have the desired structure and functional properties suitable for uniform cell distribution and stable shape fidelity in the full period of in vitro culture and in vivo implantation.However,due to insufficient cell infiltration and inadequate mechanical properties,engineered tissue made from porous scaffolds may have an inconsistent cellular composition and a poor shape retainability,which seriously hinders their further clinical application.In this study,silk fibroin was integrated with silk short fibers with a physical and chemical double-crosslinking network to fabricate fiber-reinforced silk fibroin super elastic absorbent sponges(Fr-SF-SEAs).The Fr-SF-SEAs exhibited the desirable synergistic properties of a honeycomb structure,hygroscopicity and elasticity,which allowed them to undergo an unconventional cyclic compression inoculation method to significantly promote cell diffusion and achieve a uniform cell distribution at a high-density.Furthermore,the regenerated cartilage of the Fr-SF-SEAs scaffold withstood a dynamic pressure environment after subcutaneous implantation and maintained its precise original structure,ultimately achieving human-scale ear-shaped cartilage regeneration.Importantly,the SF-SEAs prepara-tion showed valuable universality in combining chemicals with other bioactive materials or drugs with reactive groups to construct microenvironment bionic scaffolds.The established novel cell inoculation method is highly versatile and can be readily applied to various cells.Based on the design concept of dual-network Fr-SF-SEAs scaffolds,homogenous and mature cartilage was successfully regenerated with precise and complicated shapes,which hopefully provides a platform strategy for tissue engineering for various cartilage defect repairs.
基金supported by the National Key Research and Development Program of China(2022YFA1207500)the National Key Research and Development Program of China(2022YFC2409803)+3 种基金Biomaterials and Regenerative Medicine Institute Cooperative Research Project of Shanghai Jiaotong University School of Medicine(2022LHA07)the National Natural Science Foundation of China(82102211)Experimental Animal Research Project of Shanghai Science and Technology Commission(No.22140901200)Shanghai Municipal Key Clinical Specialty(shslczdzk06601).
文摘The biomedical application of self-healing materials in wet or(under)water environments is quite challenging because the insulation and dissociation effects of water molecules significantly reduce the reconstruction of material–interface interactions.Rapid closure with uniform tension of high-tension wounds is often difficult,leading to further deterioration and scarring.Herein,a new type of thermosetting water-resistant self-healing bioelastomer(WRSHE)was designed by synergistically incorporating a stable polyglycerol sebacate(PGS)covalent crosslinking network and triple hybrid dynamic networks consisting of reversible disulfide metathesis(SS),and dimethylglyoxime urethane(Dou)and hydrogen bonds.And a resveratrol-loaded WRSHE(Res@WRSHE)was developed by a swelling,absorption,and crosslinked network locking strategy.WRSHEs exhibited skin-like mechanical properties in terms of nonlinear modulus behavior,biomimetic softness,high stretchability,and good elasticity,and they also achieved ultrafast and highly efficient self-healing in various liquid environments.For wound-healing applications of high-tension full-thickness skin defects,the convenient surface assembly by self-healing of WRSHEs provides uniform contraction stress to facilitate tight closure.Moreover,Res@WRSHEs gradually release resveratrol,which helps inflammatory response reduction,promotes blood vessel regeneration,and accelerates wound repair.
