Herein,copper ion doped calcium alginate(Cu^(2+)/CaAlg)composite hydrogel filtration membranes were prepared by using natural polymer sodium alginate(NaAlg)as raw material.The thermal stability and structure of the co...Herein,copper ion doped calcium alginate(Cu^(2+)/CaAlg)composite hydrogel filtration membranes were prepared by using natural polymer sodium alginate(NaAlg)as raw material.The thermal stability and structure of the composite membranes were characterized by thermogravimetric analysis and infrared spectroscopy.The mechanical strength,anti-fouling performance,hydrophilicity and filtration performance of the membrane were studied.The results show that Cu^(2+)/CaAlg hydrogel membrane has excelle nt mechanical properties and thermal stability.The anti-swelling ability of the membrane was greatly enhanced by doping Cu^(2+).After three alternate filtration cycles,the flux recovery rate of Cu^(2+)/CaAlg hydrogel membrane can still reach 85%,indicating that the membrane has good antipollution performance.When the operation pressure was 0.1 MPa,the rejection of coomassie brilliant blue G250 reached 99.8%with a flux of 46.3 L m^(-2)h^(-1),while the Na_(2)SO_(4) rejection was less than 10.0%.The Cu^(2+)/CaAlg membrane was recycled after 24 h in the filtration process,and its flux and rejection rate did not decrease significantly,indicating that the hydrogel membrane has long-term application potential.The Cu^(2+)/CaAlg membrane has a wide range of applications prospect in dye desalination,fine separation and biopharmaceutical technology fields.展开更多
It is challenging to cluster multi-view data in which the clusters have overlapping areas.Existing multi-view clustering methods often misclassify the indistinguishable objects in overlapping areas by forcing them int...It is challenging to cluster multi-view data in which the clusters have overlapping areas.Existing multi-view clustering methods often misclassify the indistinguishable objects in overlapping areas by forcing them into single clusters,increasing clustering errors.Our solution,the multi-view dynamic kernelized evidential clustering method(MvDKE),addresses this by assigning these objects to meta-clusters,a union of several related singleton clusters,effectively capturing the local imprecision in overlapping areas.MvDKE offers two main advantages:firstly,it significantly reduces computational complexity through a dynamic framework for evidential clustering,and secondly,it adeptly handles non-spherical data using kernel techniques within its objective function.Experiments on various datasets confirm MvDKE's superior ability to accurately characterize the local imprecision in multi-view non-spherical data,achieving better efficiency and outperforming existing methods in overall performance.展开更多
Bone,cartilage,and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types,whose activity and interplay must be precisely mediated for effective healing post-injury.Although ext...Bone,cartilage,and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types,whose activity and interplay must be precisely mediated for effective healing post-injury.Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone,cartilage,and soft tissue regeneration,effective clinical translation of these mechanisms remains a challenge.Regulation of the immune microenvironment is increasingly becoming a favorable target for bone,cartilage,and soft tissue regeneration;therefore,an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable.Herein,we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone,cartilage,and soft tissue repair and regeneration.We discuss the roles of various immune cell subsets in bone,cartilage,and soft tissue repair and regeneration processes and introduce novel strategies,for example,biomaterial-targeting of immune cell activity,aimed at regulating healing.Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone,cartilage,and soft tissue regeneration through regulation of the immune microenvironment.展开更多
Herein,we adopt a simple supramolecular strategy to effectively control the tautomerism of ureidopyrimidinone(UPy)moiety and ultimately realize the complete arrangement of enol configuration.The obtained UPy derivativ...Herein,we adopt a simple supramolecular strategy to effectively control the tautomerism of ureidopyrimidinone(UPy)moiety and ultimately realize the complete arrangement of enol configuration.The obtained UPy derivatives containing self-complementary quadruple hydrogen bonding interactions can spontaneously self-assemble towards the formation of well-controlled,self-organized supramolecular nanostructure morphologies in both chloroform and water.The resulting aggregates had been fully characterized by various spectroscopy(absorption,emission)and microscopy(TEM,SEM and AFM)studies.It is anticipated that this study can provide an exact and excellent monomeric unit for controllable and precise supramolecular polymerization.The results achieved here also demonstrate the utility and feasibility of multiple hydrogen bonds to direct the self-assembly of small-molecule building blocks in aqueous media,which provides a strategy for the construction of well-defined and stable supramolecular architectures with chemical functionalities and physical properties as advanced materials for biological applications.展开更多
Ferroptosis plays a crucial role in the progression of diabetic wounds,suggesting potential therapeutic strategies to target ferroptosis.Transient receptor potential ankyrin 1(TRPA1)is a non-selective calcium channel ...Ferroptosis plays a crucial role in the progression of diabetic wounds,suggesting potential therapeutic strategies to target ferroptosis.Transient receptor potential ankyrin 1(TRPA1)is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli.Cinnamaldehyde(CA)is a specific TRPA1 agonist.In in vitro experiments,we observed that high glucose(HG)treatment induced endothelial cell ferroptosis,impairing cell function.CA successfully inhibited endothelial cell ferroptosis,improving migration,proliferation,and tube formation.Further mechanistic studies showed that CA-activated TRPA1-induced Ca^(2+)influx promoted the phosphorylation of calmodulin-dependent protein kinase II(CaMKII)and nuclear factor-E 2-related factor 2(Nrf2)translocation,which contributed to the elevation of glutathione peroxidase 4(GPX4),leading to the in-hibition of endothelial cell ferroptosis.In addition,CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel(CA@HA-Gel),allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner.The results showed that CA@HA-Gel inhibited wound endothelial cell fer-roptosis and significantly promoted diabetic wound healing.In summary,the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.展开更多
A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage....A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage.Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site.In the present study,we achieved an enriched concentration of PD-L1 from exosomes(Exos)of a genetically engineered Human Umbilical Vein Endothelial Cell(HUVECs),and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface,suppressing the activation of T cells.Furthermore,exosomal PD-L1 induced Mesenchymal Stem Cells(MSCs)towards osteogenic differentiation when pre-cultured with T cells.Moreover,embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner.Additionally,exosomal PD-L1,embedded in a hydrogel,markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase.Importantly,our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites,while T cells in distant immune organs such as the spleen were not affected.In summary,this study provides the first example of using PD-L1-enriched Exos for bone fracture repair,and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.展开更多
It is imperative to develop and implement newer,more effective strategies to address refractory diabetic wounds.As of now,there is currently no optimal solution for these wounds.Hypoxic human umbilical vein endothelia...It is imperative to develop and implement newer,more effective strategies to address refractory diabetic wounds.As of now,there is currently no optimal solution for these wounds.Hypoxic human umbilical vein endothelial cells(HUVECs)-derived exosomes have been postulated to promote diabetic wound healing,however,its effect and molecular mechanism need further study.In this study,we aimed to investigate whether hypoxic exosomes enhance wound healing in diabetics.Based on our high-throughput sequencing,differentially expressed lncRNAs(including 64 upregulated lncRNAs and 94 downregulated lncRNAs)were found in hypoxic exosomes compared to normoxic exosomes.Interestingly,lncHAR1B was one of the prominently upregulated lncRNAs in hypoxic exosomes,showing a notable correlation with diabetic wound healing.More specifically,hypoxic exosomes were transmitted to surrounding cells,which resulted in a significant increase in lncHAR1B level,thereby relieving the dysfunction of endothelial cells and promoting the switch from M1 to M2 macrophages under high glucose conditions.Mechanistically,lncHAR1B directly interacted with the transcription factor basic helix-loop-helix family member e23(BHLHE23),which subsequently led to its binding to the KLF transcription factor 4(KLF4)and promoted KLF4 expression.In our in vivo experiments,the use of hypoxic exosomes-loaded HGM-QCS hydrogels(Gel-H-Exos)resulted in rapid wound healing compared to that of normoxic exosomes-loaded HGM-QCS hydrogels(Gel-N-Exos)and diabetic groups.Consequently,our study provides potentially novel therapeutic approaches aimed at accelerating wound healing and developing a practical exosomes delivery platform.展开更多
Bone nonunion poses an urgent clinical challenge that needs to be addressed.Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing.Macrophages and bone marrow-derived m...Bone nonunion poses an urgent clinical challenge that needs to be addressed.Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing.Macrophages and bone marrow-derived mesenchymal stromal cells(BMSCs)are important targets for therapeutic interventions in bone fractures.Itaconate is a TCA cycle metabolite that has emerged as a potent macrophage immunomodulator that limits the inflammatory response.During osteogenic differentiation,BMSCs tend to undergo aerobic glycolysis and metabolize glucose to lactate.Copper ion(Cu^(2+))is an essential trace element that participates in glucose metabolism and may stimulate glycolysis in BMSCs and promote osteogenesis.In this study,we develop a 4-octyl itaconate(4-OI)@Cu@Gel nanocomposite hydrogel that can effectively deliver and release 4-OI and Cu^(2+)to modulate the metabolic microenvironment and improve the functions of cells involved in the fracture healing process.The findings reveal that burst release of 4-OI reduces the inflammatory response,promotes M2 macrophage polarization,and alleviates oxidative stress,while sustained release of Cu^(2+)stimulates BMSC glycolysis and osteogenic differentiation and enhances endothelial cell angiogenesis.Consequently,the 4-OI@Cu@Gel system achieves rapid fracture healing in mice.Thus,this study proposes a promising regenerative strategy to expedite bone fracture healing through metabolic reprogramming of macrophages and BMSCs.展开更多
The diabetic wounds remain to be unsettled clinically,with chronic wounds characterized by drug-resistant bacterial infections,compromised angiogenesis and oxidative damage to the microenvironment.To ameliorate oxidat...The diabetic wounds remain to be unsettled clinically,with chronic wounds characterized by drug-resistant bacterial infections,compromised angiogenesis and oxidative damage to the microenvironment.To ameliorate oxidative stress and applying antioxidant treatment in the wound site,we explore the function of folliculininteracting protein 1(FNIP1),a mitochondrial gatekeeper protein works to alter mitochondrial morphology,reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation.And our in vitro experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment.To realize the drug delivery and local regulation of FNIP1 in diabetic wound sites,a novel designed glucose-responsive HA-PBA-FA/EN106 hydrogel is introduced for improving diabetic wound healing.Due to the dynamic phenylboronate ester structure with a phenylboronic acid group between hyaluronic acid(HA)and phenylboronic acid(PBA),the hydrogel is able to realize a glucose-responsive release of drugs.Fulvic acid(FA)is added in the hydrogel,which not only severs as crosslinking agent but also provides antibacterial and anti-inflammatory abilities.Moreover,the release of FEM1b-FNIP1 axis inhibitor EN106 ameliorated oxidative stress and stimulated angiogenesis through FEM1b-FNIP1 axis regulation.These in vivo and in vitro results demonstrated that accelerated diabetic wounds repair with the use of the HA-PBA-FA/EN106 hydrogel,which may provide a promising strategy for chronic diabetic wound repair.展开更多
Diabetic wounds are a common complication in diabetes patients.Due to peripheral nerve damage and vascular dysfunction,diabetic wounds are prone to progress to local ulcers,wound gangrene and even to require amputatio...Diabetic wounds are a common complication in diabetes patients.Due to peripheral nerve damage and vascular dysfunction,diabetic wounds are prone to progress to local ulcers,wound gangrene and even to require amputation,bringing huge psychological and economic burdens to patients.However,the current treatment methods for diabetic wounds mainly include wound accessories,negative pressure drainage,skin grafting and surgery;there is still no ideal treatment to promote diabetic wound healing at present.Appropriate animal models can simulate the physiological mechanism of diabetic wounds,providing a basis for translational research in treating diabetic wound healing.Although there are no animal models that can fully mimic the pathophysiological mechanisms of diabetic wounds in humans,it is vital to explore animal simulation models used in basic research and preclinical studies of diabetic wounds.In addition,hydrogel materials are regarded as a promising treatment for diabetic wounds because of their good antimicrobial activity,biocompatibility,biodegradation and appropriate mechanical properties.Herein,we review and discuss the different animal models used to investigate the pathological mechanisms of diabetic wounds.We further discuss the promising future application of hydrogel biomaterials in diabetic wound healing.展开更多
Inspired by natural Ca^(2+)channels,we design and synthesize a type of artificial Ca^(2+)carriers using o-phenanthroline-oxadiazole-based foldamers.Through the incorporation of negative charges into cavity-containing ...Inspired by natural Ca^(2+)channels,we design and synthesize a type of artificial Ca^(2+)carriers using o-phenanthroline-oxadiazole-based foldamers.Through the incorporation of negative charges into cavity-containing foldamers,highly selective calcium ion transmembrane transport can be achieved,leading to the identification of two highly efficient Ca^(2+)carriers.Systematic investigation revealed a positive correlation between the number of negative charges on the foldamers and the foldamers‘cation-binding affinity.Furthermore,the size-selective effect,achieved through precise matching between the foldamer cavity dimensions and Ca^(2+)ion size,resulted in an unprecedented Ca^(2+)/Mg^(2+)selectivity ratio(S_(Ca/Mg)),reaching record S_(Ca/Mg) values greater than 100–the highest of all artificial Ca^(2+)carriers reported to date.Moreover,artificial Ca^(2+)carriers show high Ca^(2+)transport activity(EC_(50)=190 nM).This simple and modular approach enables tailored design of divalent cation transporters,thus providing promising applications for artificial divalent cation transporters in the fields of biochemistry and material chemistry.展开更多
Reducing the amount of zinc oxide(ZnO)is a continuous pursuit of the rubber industry because of the high cost and environmental pollution of Zn.However,reducing the amount of ZnO will inevitably lead to a decrease in ...Reducing the amount of zinc oxide(ZnO)is a continuous pursuit of the rubber industry because of the high cost and environmental pollution of Zn.However,reducing the amount of ZnO will inevitably lead to a decrease in the crosslinking density and the loss of mechanical properties of rubber;thus,this remains a huge challenge.Herein,we prepared Zn single-atoms supported on graphene oxide(Zn SAs@GO)as controlled-release catalysts for effective rubber vulcanization,which can improve the crosslinking density and mechanical properties of rubber by reducing Zn dosage compared to commercial ZnO by 82.5%.X-ray absorption spectroscopy(XAS)analysis reveals that Zn±O bond is 2.03 A in Zn SAs@GO,which possesses moderate Zn±O binding energy.Thus Zn^(2+)ions can be controlled-release and participate in the vulcanization reaction with higher activity.Moreover,due to the homogeneous dispersion of Zn atoms in Zn SAs@GO,zinc catalysts were fully utilized during the vulcanization process,resulting in a 6.6%increase in crosslinking density of the prepared vulcanized rubber compared to that of commercial ZnO.This work contributes to the development of large-scale preparation for SACs and potentially pave the way for their applications in industrial rubber manufacture.展开更多
Diabetic conditions impair bone regeneration due to dysregulated macrophage polarization and inflammatory imbalance.Current therapies often fail to address systemic immune homeostasis.Herein,a bone-targeted nanoplatfo...Diabetic conditions impair bone regeneration due to dysregulated macrophage polarization and inflammatory imbalance.Current therapies often fail to address systemic immune homeostasis.Herein,a bone-targeted nanoplatform(abbreviated as AgSr-MSNs)is engineered to scavenge excess nitric oxide(NO)and respond to the acidic diabetic microenvironment based on upregulated inducible nitric oxide synthase(iNOS)expression in M1 macrophages residing within both the diabetic bone marrow and localized osteolytic regions in our study.The system integrates silver sulfide quantum dots(Ag2S QDs)and Sr^(2+)into mesoporous silica nanoparticles(MSNs),encapsulated with rhodamine/β-cyclodextrin and surface-modified with alendronate for bone-specific targeting.Under near-infrared(NIR)irradiation,the nanoparticles induce macrophage repolarization toward M2 phenotypes through JAK/STAT signaling pathway,followed by upregulating anti-inflammatory mediators(TGF-β,PD-L1)and tissue-regenerative factors(BMP-2/4,VEGF-B),while suppressing pro-inflammatory cytokines(CCR2,S100A4).This dual NO/pH-responsive platform synergistically mitigates inflammatory dysregu-lation,enhances osteogenesis,and promotes angiogenesis.In diabetic models,systemic administration with NIRmediated mild hyperthermia reduces CD86^(+)macrophages and TNF-αlevels while elevating CD206^(+)macrophages locally and systemically.Concurrently,it boosts CD31,Runx2,and osteocalcin(OCN)expression levels at defect sites,indicating restored vascularization and osteogenesis.This strategy addresses the pathological triad of diabetic osteopathy-chronic inflammation,vascular insufficiency,and osteogenic impairment-providing a translatable nanotherapeutic paradigm for metabolic bone disorders.展开更多
Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or st...Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA;QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.展开更多
Wheat ear counting is a prerequisite for the evaluation of wheat yield.A wheat ear counting method based on frequency domain decomposition is proposed in this study to improve the accuracy of wheat yield estimation.Th...Wheat ear counting is a prerequisite for the evaluation of wheat yield.A wheat ear counting method based on frequency domain decomposition is proposed in this study to improve the accuracy of wheat yield estimation.The frequency domain decomposition of wheat ear image is completed by multiscale support value filter(MSVF)combined with improved sampled contourlet transform(ISCT).Support Vector Machine(SVM)is the classic classification and regression algorithm of machine learning.MSVF based on this has strong frequency domain filtering and generalization ability,which can effectively remove the complex background,while the multi-direction characteristics of ISCT enable it to represent the contour and texture information of wheat ears.In order to improve the level of wheat yield prediction,MSVF-ISCT method is used to decompose the ear image in multiscale and multi direction in frequency domain,reduce the interference of irrelevant information,and generate the sub-band image with more abundant information components of ear feature information.Then,the ear feature is extracted by morphological operation and maximum entropy threshold segmentation,and the skeleton thinning and corner detection algorithms are used to count the results.The number of wheat ears in the image can be accurately counted.Experiments show that compared with the traditional algorithms based on spatial domain,this method significantly improves the accuracy of wheat ear counting,which can provide guidance and application for the field of agricultural precision yield estimation.展开更多
Oxidative stress,infection,and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus(DM).In recent times,the discovery of neddylation,a new t...Oxidative stress,infection,and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus(DM).In recent times,the discovery of neddylation,a new type of post-translational modification,has been found to regulate various crucial biological processes including cell metabolism and the cell cycle.Nevertheless,its capacity to control the healing of wounds in diabetic patients remains unknown.This study shows that MLN49224,a compound that inhibits neddylation at low concentrations,enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors.Moreover,it concurrently stimulates the growth,movement,and formation of blood vessel endothelial cells,leading to expedited healing of wounds in individuals with diabetes.The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles(M-NPs/MLN4924).The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area.The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes,along with the polarization of macrophages towards the anti-inflammatory M2 phenotype.By loading M-NPs/MLN4924 into a hydrogel,the final formulation is able to meaningfully repair a diabetic wound,suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.展开更多
The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in ...The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and mice.This effect was attributed to VPA-induced elevation in osteoclast formation and activity.Through RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive activity.Additionally,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone loss.Currently,there are no medications that can effectively treat VPA-induced bone loss.Therefore,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 sequence.We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.展开更多
The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immu...The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.展开更多
The efficiency of proton exchange membrane water electrolysis(PEM-WE)for hydrogen production is heavily dependent on the noble metal iridium-based catalysts.However,the scarcity of iridium limits the large-scale appli...The efficiency of proton exchange membrane water electrolysis(PEM-WE)for hydrogen production is heavily dependent on the noble metal iridium-based catalysts.However,the scarcity of iridium limits the large-scale application of PEM-WE.To address this issue,it is promising to select an appropriate support because it not only enhances the utilization efficiency of noble metals but also improves mass transport under high current.Herein,we supported amorphous IrO_(x) nanosheets onto the hollow TiO_(2) sphere(denoted as IrO_(x)),which demonstrated excellent performance in acidic electrolytic water splitting.Specifically,the annealed IrO_(x)catalyst at 150℃in air exhibited a mass activity of 1347.5 A·gIr^(−1),which is much higher than that of commercial IrO_(2) of 12.33 A·gIr^(−1) at the overpotential of 300 mV for oxygen evolution reaction(OER).Meanwhile,the annealed IrO_(x) exhibited good stability for 600 h operating at 10 mA·cm^(−2).Moreover,when using IrO_(x) and annealed IrO_(x) catalysts for water splitting,a cell voltage as low as 1.485 V can be achieved at 10 mA·cm^(−2).The cell can continuously operate for 200 h with negligible degradation of performance.展开更多
To understand the relationships between channel size and ion selectivity,we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthrolineoxadiazole units with ...To understand the relationships between channel size and ion selectivity,we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthrolineoxadiazole units with a pore aperture 2.3A close to the diameter of the Na^(+)ion(2.04A).Successful preparation of high molecular weight helical polymers(HP1)gives rise to a 4.6 nm long artificial unimolecular transmembrane channel.The transport property of artificial channel HP1 was elaborately investigated by means of vesicle-based kinetic assay and symmetry/asymmetry bilayer membrane(BLM)experiments as well.These results unambiguously demonstrate that HP1 is a Na^(+)-selective channel with extremely high transport activity(EC_(50)=0.017 mol% relative to lipid).Moreover,the Na^(+)/K^(+)selectivity ratio of HP1 reaches 1.9,as determined by asymmetry BLM experiments.Owing to the narrowest 2.3A size constraint so far,HP1 transport naked Na^(+)ion across the membrane,which represents a different Na^(+)transport mode from that of natural Na^(+)channels,which transports partially hydrated Na^(+)ions during transmembrane conduction.This study provides crucial insights on the chemical basis of ion selectivity in the field of ion channels.展开更多
基金supported by National Natural Science Foundation of China(Nos.51678409,51708406,51708407)Tianjin Science Technology Research Funds of China(Nos.16JCZDJC37500,15JCZDJC38300)Tianjin Science and Technology Plan Project(No.18ZXJMTG00120)。
文摘Herein,copper ion doped calcium alginate(Cu^(2+)/CaAlg)composite hydrogel filtration membranes were prepared by using natural polymer sodium alginate(NaAlg)as raw material.The thermal stability and structure of the composite membranes were characterized by thermogravimetric analysis and infrared spectroscopy.The mechanical strength,anti-fouling performance,hydrophilicity and filtration performance of the membrane were studied.The results show that Cu^(2+)/CaAlg hydrogel membrane has excelle nt mechanical properties and thermal stability.The anti-swelling ability of the membrane was greatly enhanced by doping Cu^(2+).After three alternate filtration cycles,the flux recovery rate of Cu^(2+)/CaAlg hydrogel membrane can still reach 85%,indicating that the membrane has good antipollution performance.When the operation pressure was 0.1 MPa,the rejection of coomassie brilliant blue G250 reached 99.8%with a flux of 46.3 L m^(-2)h^(-1),while the Na_(2)SO_(4) rejection was less than 10.0%.The Cu^(2+)/CaAlg membrane was recycled after 24 h in the filtration process,and its flux and rejection rate did not decrease significantly,indicating that the hydrogel membrane has long-term application potential.The Cu^(2+)/CaAlg membrane has a wide range of applications prospect in dye desalination,fine separation and biopharmaceutical technology fields.
基金supported in part by the Youth Foundation of Shanxi Province(5113240053)the Fundamental Research Funds for the Central Universities(G2023KY05102)+2 种基金the Natural Science Foundation of China(61976120)the Natural Science Foundation of Jiangsu Province(BK20231337)the Natural Science Key Foundation of Jiangsu Education Department(21KJA510004)。
文摘It is challenging to cluster multi-view data in which the clusters have overlapping areas.Existing multi-view clustering methods often misclassify the indistinguishable objects in overlapping areas by forcing them into single clusters,increasing clustering errors.Our solution,the multi-view dynamic kernelized evidential clustering method(MvDKE),addresses this by assigning these objects to meta-clusters,a union of several related singleton clusters,effectively capturing the local imprecision in overlapping areas.MvDKE offers two main advantages:firstly,it significantly reduces computational complexity through a dynamic framework for evidential clustering,and secondly,it adeptly handles non-spherical data using kernel techniques within its objective function.Experiments on various datasets confirm MvDKE's superior ability to accurately characterize the local imprecision in multi-view non-spherical data,achieving better efficiency and outperforming existing methods in overall performance.
基金supported by the National Natural Science Foundation of China(82002313,82072444,31900963)the Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration(2020kqhm008,2021kqhm002)+2 种基金the Health Commission of Hubei Province(WJ2019Z009)the Wuhan Union Hospital“Pharmaceutical Technology Nursing”special fund(2019xhyn021),the China Postdoctoral Science Foundation(2021TQ0118)the Gillian Reny Stepping Strong Center for Trauma Innovation Research Scholars Fund(110768).
文摘Bone,cartilage,and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types,whose activity and interplay must be precisely mediated for effective healing post-injury.Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone,cartilage,and soft tissue regeneration,effective clinical translation of these mechanisms remains a challenge.Regulation of the immune microenvironment is increasingly becoming a favorable target for bone,cartilage,and soft tissue regeneration;therefore,an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable.Herein,we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone,cartilage,and soft tissue repair and regeneration.We discuss the roles of various immune cell subsets in bone,cartilage,and soft tissue repair and regeneration processes and introduce novel strategies,for example,biomaterial-targeting of immune cell activity,aimed at regulating healing.Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone,cartilage,and soft tissue regeneration through regulation of the immune microenvironment.
基金supported by the National Natural Science Foundation of China(Nos.22071078,92156012 and 21722403)the Program for JLU Science and Technology Innovative Research Team(JLUSTIRT,No.2019TD-36)。
文摘Herein,we adopt a simple supramolecular strategy to effectively control the tautomerism of ureidopyrimidinone(UPy)moiety and ultimately realize the complete arrangement of enol configuration.The obtained UPy derivatives containing self-complementary quadruple hydrogen bonding interactions can spontaneously self-assemble towards the formation of well-controlled,self-organized supramolecular nanostructure morphologies in both chloroform and water.The resulting aggregates had been fully characterized by various spectroscopy(absorption,emission)and microscopy(TEM,SEM and AFM)studies.It is anticipated that this study can provide an exact and excellent monomeric unit for controllable and precise supramolecular polymerization.The results achieved here also demonstrate the utility and feasibility of multiple hydrogen bonds to direct the self-assembly of small-molecule building blocks in aqueous media,which provides a strategy for the construction of well-defined and stable supramolecular architectures with chemical functionalities and physical properties as advanced materials for biological applications.
基金supported by the National Science Foundation of China(No.82272491,No.82072444)Award Program for outstanding recent Ph.D.Graduates at Wuhan Union Hospital(2022)and Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Trans-lational Research(2022zsyx009)+1 种基金Chinese Pharmaceutical Association Hospital Pharmacy Department(No.CPA-Z05-ZC-2022-002)Hubei Province Unveiling Science and Technology Projects(No.2022-35).
文摘Ferroptosis plays a crucial role in the progression of diabetic wounds,suggesting potential therapeutic strategies to target ferroptosis.Transient receptor potential ankyrin 1(TRPA1)is a non-selective calcium channel that acts as a receptor for a variety of physical or chemical stimuli.Cinnamaldehyde(CA)is a specific TRPA1 agonist.In in vitro experiments,we observed that high glucose(HG)treatment induced endothelial cell ferroptosis,impairing cell function.CA successfully inhibited endothelial cell ferroptosis,improving migration,proliferation,and tube formation.Further mechanistic studies showed that CA-activated TRPA1-induced Ca^(2+)influx promoted the phosphorylation of calmodulin-dependent protein kinase II(CaMKII)and nuclear factor-E 2-related factor 2(Nrf2)translocation,which contributed to the elevation of glutathione peroxidase 4(GPX4),leading to the in-hibition of endothelial cell ferroptosis.In addition,CA was incorporated into an MMP-9-responsive injectable duplex hybrid hydrogel(CA@HA-Gel),allowing its efficient sustained release into diabetic wounds in an inflammation-responsive manner.The results showed that CA@HA-Gel inhibited wound endothelial cell fer-roptosis and significantly promoted diabetic wound healing.In summary,the results presented in this study emphasize the potential therapeutic application of CA@HA-Gel in the treatment of diseases associated with ferroptosis.
基金This work was supported by the National Science Foundation of China(No.82002313,No.82072444,31900963)Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration(No.2020kqhm008)+2 种基金the Health Commission of Hubei Province(No.WJ2019Z009)the Wuhan Union Hospital"Pharmaceutical Technology nursing"special fund(No.2019xhyn021)the China Postdoctoral Science Foundation(No.2021TQ0118).
文摘A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage.Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site.In the present study,we achieved an enriched concentration of PD-L1 from exosomes(Exos)of a genetically engineered Human Umbilical Vein Endothelial Cell(HUVECs),and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface,suppressing the activation of T cells.Furthermore,exosomal PD-L1 induced Mesenchymal Stem Cells(MSCs)towards osteogenic differentiation when pre-cultured with T cells.Moreover,embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner.Additionally,exosomal PD-L1,embedded in a hydrogel,markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase.Importantly,our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites,while T cells in distant immune organs such as the spleen were not affected.In summary,this study provides the first example of using PD-L1-enriched Exos for bone fracture repair,and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.
基金supported by the National Science Foundation of China(No.82272491,No.82072444)Chinese Pharmaceutical Association Hospital Pharmacy department(No.CPA-Z05-ZC-2022-002)Grants from Hubei Province Unveiling Science and Technology Projects(No.2022-35).
文摘It is imperative to develop and implement newer,more effective strategies to address refractory diabetic wounds.As of now,there is currently no optimal solution for these wounds.Hypoxic human umbilical vein endothelial cells(HUVECs)-derived exosomes have been postulated to promote diabetic wound healing,however,its effect and molecular mechanism need further study.In this study,we aimed to investigate whether hypoxic exosomes enhance wound healing in diabetics.Based on our high-throughput sequencing,differentially expressed lncRNAs(including 64 upregulated lncRNAs and 94 downregulated lncRNAs)were found in hypoxic exosomes compared to normoxic exosomes.Interestingly,lncHAR1B was one of the prominently upregulated lncRNAs in hypoxic exosomes,showing a notable correlation with diabetic wound healing.More specifically,hypoxic exosomes were transmitted to surrounding cells,which resulted in a significant increase in lncHAR1B level,thereby relieving the dysfunction of endothelial cells and promoting the switch from M1 to M2 macrophages under high glucose conditions.Mechanistically,lncHAR1B directly interacted with the transcription factor basic helix-loop-helix family member e23(BHLHE23),which subsequently led to its binding to the KLF transcription factor 4(KLF4)and promoted KLF4 expression.In our in vivo experiments,the use of hypoxic exosomes-loaded HGM-QCS hydrogels(Gel-H-Exos)resulted in rapid wound healing compared to that of normoxic exosomes-loaded HGM-QCS hydrogels(Gel-N-Exos)and diabetic groups.Consequently,our study provides potentially novel therapeutic approaches aimed at accelerating wound healing and developing a practical exosomes delivery platform.
基金supported by the National Natural Science Foundation of China (No.82272491,82072444,82202676).
文摘Bone nonunion poses an urgent clinical challenge that needs to be addressed.Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing.Macrophages and bone marrow-derived mesenchymal stromal cells(BMSCs)are important targets for therapeutic interventions in bone fractures.Itaconate is a TCA cycle metabolite that has emerged as a potent macrophage immunomodulator that limits the inflammatory response.During osteogenic differentiation,BMSCs tend to undergo aerobic glycolysis and metabolize glucose to lactate.Copper ion(Cu^(2+))is an essential trace element that participates in glucose metabolism and may stimulate glycolysis in BMSCs and promote osteogenesis.In this study,we develop a 4-octyl itaconate(4-OI)@Cu@Gel nanocomposite hydrogel that can effectively deliver and release 4-OI and Cu^(2+)to modulate the metabolic microenvironment and improve the functions of cells involved in the fracture healing process.The findings reveal that burst release of 4-OI reduces the inflammatory response,promotes M2 macrophage polarization,and alleviates oxidative stress,while sustained release of Cu^(2+)stimulates BMSC glycolysis and osteogenic differentiation and enhances endothelial cell angiogenesis.Consequently,the 4-OI@Cu@Gel system achieves rapid fracture healing in mice.Thus,this study proposes a promising regenerative strategy to expedite bone fracture healing through metabolic reprogramming of macrophages and BMSCs.
基金the National Science Foundation of China(No.82272491,No.82072444)the Wuhan Science and Technology Bureau(2022020801020464)+2 种基金the Department of Science and Technology of Hubei Province(No.2021CFB425)Chinese Pharmaceutical Association Hospital Phamacy department(No.CPA-Z05-ZC-2022-002)Grants from Hubei Province Unveiling Science and Technology Projects(No.2022-35).
文摘The diabetic wounds remain to be unsettled clinically,with chronic wounds characterized by drug-resistant bacterial infections,compromised angiogenesis and oxidative damage to the microenvironment.To ameliorate oxidative stress and applying antioxidant treatment in the wound site,we explore the function of folliculininteracting protein 1(FNIP1),a mitochondrial gatekeeper protein works to alter mitochondrial morphology,reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation.And our in vitro experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment.To realize the drug delivery and local regulation of FNIP1 in diabetic wound sites,a novel designed glucose-responsive HA-PBA-FA/EN106 hydrogel is introduced for improving diabetic wound healing.Due to the dynamic phenylboronate ester structure with a phenylboronic acid group between hyaluronic acid(HA)and phenylboronic acid(PBA),the hydrogel is able to realize a glucose-responsive release of drugs.Fulvic acid(FA)is added in the hydrogel,which not only severs as crosslinking agent but also provides antibacterial and anti-inflammatory abilities.Moreover,the release of FEM1b-FNIP1 axis inhibitor EN106 ameliorated oxidative stress and stimulated angiogenesis through FEM1b-FNIP1 axis regulation.These in vivo and in vitro results demonstrated that accelerated diabetic wounds repair with the use of the HA-PBA-FA/EN106 hydrogel,which may provide a promising strategy for chronic diabetic wound repair.
基金supported by National Natural Sciences Foundation of China(Nos.82002313,82072444)Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration(No.2020kqhm008).
文摘Diabetic wounds are a common complication in diabetes patients.Due to peripheral nerve damage and vascular dysfunction,diabetic wounds are prone to progress to local ulcers,wound gangrene and even to require amputation,bringing huge psychological and economic burdens to patients.However,the current treatment methods for diabetic wounds mainly include wound accessories,negative pressure drainage,skin grafting and surgery;there is still no ideal treatment to promote diabetic wound healing at present.Appropriate animal models can simulate the physiological mechanism of diabetic wounds,providing a basis for translational research in treating diabetic wound healing.Although there are no animal models that can fully mimic the pathophysiological mechanisms of diabetic wounds in humans,it is vital to explore animal simulation models used in basic research and preclinical studies of diabetic wounds.In addition,hydrogel materials are regarded as a promising treatment for diabetic wounds because of their good antimicrobial activity,biocompatibility,biodegradation and appropriate mechanical properties.Herein,we review and discuss the different animal models used to investigate the pathological mechanisms of diabetic wounds.We further discuss the promising future application of hydrogel biomaterials in diabetic wound healing.
基金supported by the National Natural Science Foundation of China(Nos.22471093,92156012 and 22071078).
文摘Inspired by natural Ca^(2+)channels,we design and synthesize a type of artificial Ca^(2+)carriers using o-phenanthroline-oxadiazole-based foldamers.Through the incorporation of negative charges into cavity-containing foldamers,highly selective calcium ion transmembrane transport can be achieved,leading to the identification of two highly efficient Ca^(2+)carriers.Systematic investigation revealed a positive correlation between the number of negative charges on the foldamers and the foldamers‘cation-binding affinity.Furthermore,the size-selective effect,achieved through precise matching between the foldamer cavity dimensions and Ca^(2+)ion size,resulted in an unprecedented Ca^(2+)/Mg^(2+)selectivity ratio(S_(Ca/Mg)),reaching record S_(Ca/Mg) values greater than 100–the highest of all artificial Ca^(2+)carriers reported to date.Moreover,artificial Ca^(2+)carriers show high Ca^(2+)transport activity(EC_(50)=190 nM).This simple and modular approach enables tailored design of divalent cation transporters,thus providing promising applications for artificial divalent cation transporters in the fields of biochemistry and material chemistry.
基金supported by the Ministry of Science and Technology of China (2020YFA0710203)the Major Frontier Research Project of the University of Science and Technology of China (LS2060000002)+5 种基金the Joint Funds of the National Natural Science Foundation of China (U23A2081)the National Natural Science Foundation of China (22221003)the Anhui Provincial Key Research and Development Project (2023z04020010)the Anhui Provincial Natural Science Foundation (2108085UD06, 2208085UD04)the USTC Research Funds of the Double First-Class Initiative (YD2060006005)the Experimental Center of Engineering and Material Science in the University of Science and Technology of China for the support。
文摘Reducing the amount of zinc oxide(ZnO)is a continuous pursuit of the rubber industry because of the high cost and environmental pollution of Zn.However,reducing the amount of ZnO will inevitably lead to a decrease in the crosslinking density and the loss of mechanical properties of rubber;thus,this remains a huge challenge.Herein,we prepared Zn single-atoms supported on graphene oxide(Zn SAs@GO)as controlled-release catalysts for effective rubber vulcanization,which can improve the crosslinking density and mechanical properties of rubber by reducing Zn dosage compared to commercial ZnO by 82.5%.X-ray absorption spectroscopy(XAS)analysis reveals that Zn±O bond is 2.03 A in Zn SAs@GO,which possesses moderate Zn±O binding energy.Thus Zn^(2+)ions can be controlled-release and participate in the vulcanization reaction with higher activity.Moreover,due to the homogeneous dispersion of Zn atoms in Zn SAs@GO,zinc catalysts were fully utilized during the vulcanization process,resulting in a 6.6%increase in crosslinking density of the prepared vulcanized rubber compared to that of commercial ZnO.This work contributes to the development of large-scale preparation for SACs and potentially pave the way for their applications in industrial rubber manufacture.
基金the National Natural Science Foundation of China(No.82372406)Hubei Provincial Natural Science Foundation(No.2025AFB872)+1 种基金the Fundamental Reseach Funds for the Central Universities(No.YCJJ20241103)the Open Foundation of Hubei Key Laboratory of Biological Targeted Therapy(No.202412)。
文摘Diabetic conditions impair bone regeneration due to dysregulated macrophage polarization and inflammatory imbalance.Current therapies often fail to address systemic immune homeostasis.Herein,a bone-targeted nanoplatform(abbreviated as AgSr-MSNs)is engineered to scavenge excess nitric oxide(NO)and respond to the acidic diabetic microenvironment based on upregulated inducible nitric oxide synthase(iNOS)expression in M1 macrophages residing within both the diabetic bone marrow and localized osteolytic regions in our study.The system integrates silver sulfide quantum dots(Ag2S QDs)and Sr^(2+)into mesoporous silica nanoparticles(MSNs),encapsulated with rhodamine/β-cyclodextrin and surface-modified with alendronate for bone-specific targeting.Under near-infrared(NIR)irradiation,the nanoparticles induce macrophage repolarization toward M2 phenotypes through JAK/STAT signaling pathway,followed by upregulating anti-inflammatory mediators(TGF-β,PD-L1)and tissue-regenerative factors(BMP-2/4,VEGF-B),while suppressing pro-inflammatory cytokines(CCR2,S100A4).This dual NO/pH-responsive platform synergistically mitigates inflammatory dysregu-lation,enhances osteogenesis,and promotes angiogenesis.In diabetic models,systemic administration with NIRmediated mild hyperthermia reduces CD86^(+)macrophages and TNF-αlevels while elevating CD206^(+)macrophages locally and systemically.Concurrently,it boosts CD31,Runx2,and osteocalcin(OCN)expression levels at defect sites,indicating restored vascularization and osteogenesis.This strategy addresses the pathological triad of diabetic osteopathy-chronic inflammation,vascular insufficiency,and osteogenic impairment-providing a translatable nanotherapeutic paradigm for metabolic bone disorders.
基金the National Natural Science Foundation of China(No.82002313,No.82072444)China Postdoctoral Science Foundation(No.2021M701333)+1 种基金Department of Science and Technology of Hubei Province(No.2021CFB425,No.2020BCB004)Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration(2021kqhm007).
文摘Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA;QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.
基金National Natural Science Foundation of China(61672032)National Key Research and Development Program of China(2016YFD0800904)+1 种基金Anhui Provincial Science and Technology Project(16030701091)The Open Research Fund of National Engineering Research Center for Agro-Ecological Big Data Analysis&Application,Anhui University(AE2018009).
文摘Wheat ear counting is a prerequisite for the evaluation of wheat yield.A wheat ear counting method based on frequency domain decomposition is proposed in this study to improve the accuracy of wheat yield estimation.The frequency domain decomposition of wheat ear image is completed by multiscale support value filter(MSVF)combined with improved sampled contourlet transform(ISCT).Support Vector Machine(SVM)is the classic classification and regression algorithm of machine learning.MSVF based on this has strong frequency domain filtering and generalization ability,which can effectively remove the complex background,while the multi-direction characteristics of ISCT enable it to represent the contour and texture information of wheat ears.In order to improve the level of wheat yield prediction,MSVF-ISCT method is used to decompose the ear image in multiscale and multi direction in frequency domain,reduce the interference of irrelevant information,and generate the sub-band image with more abundant information components of ear feature information.Then,the ear feature is extracted by morphological operation and maximum entropy threshold segmentation,and the skeleton thinning and corner detection algorithms are used to count the results.The number of wheat ears in the image can be accurately counted.Experiments show that compared with the traditional algorithms based on spatial domain,this method significantly improves the accuracy of wheat ear counting,which can provide guidance and application for the field of agricultural precision yield estimation.
基金supported by the National Science Foundation of China(No.82272491,No.82072444)the Wuhan Science and Technology Bureau(2022020801020464)+5 种基金the Department of Science and Technology of Hubei Province(No.2021CFB425)Chinese Pharmaceutical Association Hospital Pharmacy department(No.CPA-Z05-ZC-2022-002)Hubei Province Unveiling Science and Technology Projects(No.2022-35)Natural Science Foundation of Shenzhen Municipality(JCYJ20220531094802005)Medical Research Foundation of Guangdong Province(B2022242)Scientific Research Project in Health System of Pingshan District(202218).
文摘Oxidative stress,infection,and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus(DM).In recent times,the discovery of neddylation,a new type of post-translational modification,has been found to regulate various crucial biological processes including cell metabolism and the cell cycle.Nevertheless,its capacity to control the healing of wounds in diabetic patients remains unknown.This study shows that MLN49224,a compound that inhibits neddylation at low concentrations,enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors.Moreover,it concurrently stimulates the growth,movement,and formation of blood vessel endothelial cells,leading to expedited healing of wounds in individuals with diabetes.The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles(M-NPs/MLN4924).The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area.The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes,along with the polarization of macrophages towards the anti-inflammatory M2 phenotype.By loading M-NPs/MLN4924 into a hydrogel,the final formulation is able to meaningfully repair a diabetic wound,suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.
基金supported by the National Key Research&Development Program of China(2021YFA1101500)National Science Foundation of China(No.82002313,No.82072444)+1 种基金Department of Science and Technology of Hubei Province(2021CFB425)Wuhan Science and Technology Bureau(2022020801020464)。
文摘The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and mice.This effect was attributed to VPA-induced elevation in osteoclast formation and activity.Through RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive activity.Additionally,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone loss.Currently,there are no medications that can effectively treat VPA-induced bone loss.Therefore,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 sequence.We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.
基金This work was supported by the National Science Foundation of China(No.82002313,No.82072444,No.31900963,and No.82202714)Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration(No.2020kqhm008 and No.2021kqhm002)+3 种基金the China Postdoctoral Science Foundation(No.2022M721261,and No.2021TQ0118)Y.R.was supported by the European Research Council Consolidator Grant(ERC-CoG 819933)the LEO Foundation(LF-OC-21-000835)the European Foundation for the Study of Diabetes(EFSD)Anniversary Fund Programme.
文摘The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.
基金The National Key R&D Program of China(Nos.2018YFA0702001 and 2021YFA1500400)the National Natural Science Foundation of China(Nos.22371268 and 22175163)+2 种基金Fundamental Research Funds for the Central Universities(No.WK2060000016)Anhui Development and Reform Commission(No.AHZDCYCX-2SDT2023-07)Youth Innovation Promotion Association of the Chinese Academy of Science(No.2018494)supported this work.
文摘The efficiency of proton exchange membrane water electrolysis(PEM-WE)for hydrogen production is heavily dependent on the noble metal iridium-based catalysts.However,the scarcity of iridium limits the large-scale application of PEM-WE.To address this issue,it is promising to select an appropriate support because it not only enhances the utilization efficiency of noble metals but also improves mass transport under high current.Herein,we supported amorphous IrO_(x) nanosheets onto the hollow TiO_(2) sphere(denoted as IrO_(x)),which demonstrated excellent performance in acidic electrolytic water splitting.Specifically,the annealed IrO_(x)catalyst at 150℃in air exhibited a mass activity of 1347.5 A·gIr^(−1),which is much higher than that of commercial IrO_(2) of 12.33 A·gIr^(−1) at the overpotential of 300 mV for oxygen evolution reaction(OER).Meanwhile,the annealed IrO_(x) exhibited good stability for 600 h operating at 10 mA·cm^(−2).Moreover,when using IrO_(x) and annealed IrO_(x) catalysts for water splitting,a cell voltage as low as 1.485 V can be achieved at 10 mA·cm^(−2).The cell can continuously operate for 200 h with negligible degradation of performance.
基金supported by the National Science Foundation of China(nos.22071078 and 21722403)the Program for JLU Science and Technology Innovative Research Team(JLUSTIRT)(no.2019TD-36).
文摘To understand the relationships between channel size and ion selectivity,we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthrolineoxadiazole units with a pore aperture 2.3A close to the diameter of the Na^(+)ion(2.04A).Successful preparation of high molecular weight helical polymers(HP1)gives rise to a 4.6 nm long artificial unimolecular transmembrane channel.The transport property of artificial channel HP1 was elaborately investigated by means of vesicle-based kinetic assay and symmetry/asymmetry bilayer membrane(BLM)experiments as well.These results unambiguously demonstrate that HP1 is a Na^(+)-selective channel with extremely high transport activity(EC_(50)=0.017 mol% relative to lipid).Moreover,the Na^(+)/K^(+)selectivity ratio of HP1 reaches 1.9,as determined by asymmetry BLM experiments.Owing to the narrowest 2.3A size constraint so far,HP1 transport naked Na^(+)ion across the membrane,which represents a different Na^(+)transport mode from that of natural Na^(+)channels,which transports partially hydrated Na^(+)ions during transmembrane conduction.This study provides crucial insights on the chemical basis of ion selectivity in the field of ion channels.
