EFL preservice teachers ’ research efficacy, as perceived competence to perform tasks in research, is crucial to their research engagement. This autobiographical narrative inquiry investigates the contribution of sca...EFL preservice teachers ’ research efficacy, as perceived competence to perform tasks in research, is crucial to their research engagement. This autobiographical narrative inquiry investigates the contribution of scaffolded research practice to a female EFL preservice teacher ’s research efficacy.The data were collected through conversations, notes, journals, and portfolios. The findings suggest that teacher research efficacy was pliable through scaffolded research practice. It emerged gradually over time, in different places with social and personal interaction. The factors contributing to the emerging research efficacy were: teacher educators ’ support, peers ’ support,and research participation. The study sheds light on teacher educators and EFL preservice teachers,with the intention of establishing an inquiry-based pedagogy for M.Ed. programs.展开更多
Supercapacitor-like Na-ion batteries have attracted much attention due to the high energy density of batteries and power density of capacitors.Titanium dioxide(TiO_(2)),is a promising anode material.Its performance is...Supercapacitor-like Na-ion batteries have attracted much attention due to the high energy density of batteries and power density of capacitors.Titanium dioxide(TiO_(2)),is a promising anode material.Its performance is however seriously hindered by its low electrical conductivity and the sluggish diffusion of sodium ions(Na^(+))in the TiO_(2)matrix.Herein,this work combines porous TiO_(2)nanocubes with carbon nanotubes(CNTs)to enhance the electrical conductivity and accelerate Na^(+)diffusivity for Na-ion batteries(NIBs).In this composite,an interwoven scaffolded TiO_(2)/CNTs framework is formed to provide abundant channels and shorter diffusion pathways for electrons and ions.The in-situ X-ray diffraction and cyclic voltammetry confirm the low strain and superior transport kinetics in Na^(+)intercalation/extraction processes.In addition,the chemically bonded TiO_(2)/CNTs hybrid provides a more feasible channel for Na^(+)insertion/extraction with a much lower energy barrier.Consequently,the TiO_(2)/CNTs composite exhibits excellent electrochemical performance with a capacity of 223.4 m Ah g^(-1)at 1 C and a capacity of 142.8 m Ah g^(-1)at 10 C(3.35 A g^(-1)).The work here reveals that the combination of active materials with CNTs can largely improve the utilization efficiency and enhance their sodium storage.展开更多
Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular pro...Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.展开更多
From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganu...From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.展开更多
Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold...Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC_(50))of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal“dead ends”and“safe bets”for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogeneoxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.展开更多
Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation...Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.展开更多
Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomime...Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.展开更多
The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.T...The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.展开更多
Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength(σ_(cf))of the resultant implants,thereby shortening their service lifes-pa...Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength(σ_(cf))of the resultant implants,thereby shortening their service lifes-pan.To resolve this issue,in the present,a step-wise graded porous Ti-6Al-7Nb scaffold was additively manufactured on optimally surface mechanical attrition treated(SMATed)Ti-6Al-7Nb(specifically de-noted as S-Ti6Al7Nb)using laser powder bed fusion(PBF)technology.The microstructure,bond strength,residual stress distribution,and corrosion fatigue behavior of porous scaffolds modified S-Ti6Al7Nb were investigated and compared with those of mechanically polished Ti-6Al-7Nb(P-Ti6Al7Nb),S-Ti6Al7Nb,and porous scaffolds modified P-Ti6Al7Nb.Results showed that corrosion fatigue of porous scaffolds modi-fied Ti-6Al-7Nb was propagation controlled.Moreover,the crack propagation behavior in the PBF scaf-fold’s fusion zone(FZ)and heat-affected zone(HAZ),exhibiting insensitivity to the microstructural con-figurations characterized by columnar prior-βgrain(PBG)boundaries and acicularα''martensites,cou-pled with the PBF-induced residual tensile stresses in these regions,resulted in a considerable decrease inσ_(cf) for porous scaffolds modified P-Ti6Al7Nb compared to P-Ti6Al7Nb.In contrast,step-wise graded porous scaffold-modified S-Ti6Al7Nb demonstrated an improvedσ_(cf) which was even higher than that of P-Ti6Al7Nb.Such an advancement in corrosion fatigue strength is primarily attributed to the presence of residual compressive stresses within the underlying S-Ti6Al7Nb substrate,extending beyond FZ and HAZ.These stresses increased the crack propagation threshold,leading to crack deflection/branching and increased crack-path tortuosity,thereby synergistically markedly enhancing the crack propagation resis-tance of porous scaffolds modified S-Ti6Al7Nb.展开更多
Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and hi...Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.展开更多
Introduction It is necessary for an ideal bioceramic scaffold to have a suitable structure.The structure can affect the mechanical properties of the scaffold(i.e.,elastic modulus and compressive strength)and the biolo...Introduction It is necessary for an ideal bioceramic scaffold to have a suitable structure.The structure can affect the mechanical properties of the scaffold(i.e.,elastic modulus and compressive strength)and the biological properties of the scaffold(i.e.,degradability and cell growth rate).Lattice structure is a kind of periodic porous structure,which has some advantages of light weight and high strength,and is widely used in the preparation of bioceramic scaffolders.For the structure of the scaffold,high porosity and large pore size are important for bone growth,bone integration and promoting good mechanical interlocking between neighboring bones and the scaffold.However,scaffolds with a high porosity often lack mechanical strength.In addition,different parts of the bone have different structural requirements.In this paper,scaffolds with a non-uniform structure or a hierarchical structure were designed,with loose and porous exterior to facilitate cell adhesion,osteogenic differentiation and vascularization as well as relatively dense interior to provide sufficient mechanical support for bone repair.Methods In this work,composite ceramics scaffolds with 10%akermanite content were prepared by DLP technology.The scaffold had a high porosity outside to promote the growth of bone tissue,and a low porosity inside to withstand external forces.The compressive strength,fracture form,in-vitro degradation performance and bioactivity of graded bioceramic scaffolds were investigated.The models of scaffolds were imported into the DLP printer with a 405 nm light.The samples were printed with the intensity of 8 mJ/cm^(2)and a layer thickness of 50μm.Finally,the ceramic samples were sintered at 1100℃.The degradability of the hierarchical gyroid bioceramic scaffolds was evaluated through immersion in Tris-HCl solution and SBF solution at a ratio of 200 mL/g.The bioactivity of bioceramic was obtained via immersing them in SBF solution for two weeks.The concentrations of calcium,phosphate,silicon,and magnesium ions in the soaking solution were determined by an inductively coupled plasma optical emission spectrometer.Results and discussion In this work,a hierarchical Gyroid structure HA-AK10 scaffold(sintered at 1100℃)with a radial internal porosity of 50%and an external porosity of 70%is prepared,and the influence of structural form on the compressive strength and degradation performance of the scaffold is investigated.The biological activity of the bioceramics in vitro is also verified.The mechanical simulation results show that the stress distribution corresponds to the porosity distribution of the structure,and the low porosity is larger and the overall stress concentration phenomenon does not appear.After soaking in SBF solution,Si—OH is firstly formed on the surface of bioceramics,and then silicon gel layer is produced due to the presence of calcium and silicon ions.The silicon gel layer is dissociated into negatively charged groups under alkaline environment secondary adsorption of calcium ions and phosphate ions,forming amorphous calcium phosphate,and finally amorphous calcium phosphate crystals and adsorption of carbonate ions,forming carbonate hydroxyapatite.This indicates that the composite bioceramics have a good biological activity in-vitro and can provide a good environment for the growth of bone cells.A hierarchical Gyroid ceramic scaffold with a bone geometry is prepared via applying the hierarchical structure to the bone contour scaffold.The maximum load capacity of the hierarchical Gyroid ceramic scaffold is 8 times that of the uniform structure.Conclusions The hierarchical structure scaffold designed had good overall compressive performance,good degradation performance,and still maintained a good mechanical stability during degradation.In addition,in-vitro biological experimental results showed that the surface graded composite scaffold could have a good in-vitro biological activity and provide a good environment for bone cells.Compared to the heterosexual structure,the graded scaffold had greater mechanical properties.展开更多
Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser m...Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser melting.Their forming quality,compression mechanical properties,and degradation behavior were investigated.Results indicate that the fabricated scaffolds exhibit good dimensional accuracy,and the surface chemical polishing treatment significantly improves the forming quality and reduces porosity error in porous scaffolds.Compared to the ones with rod structures(bcc,RD),the scaffolds with surface structures(G,P)have less powder particle adhesion.The G porous scaffold exhibits the best forming quality for the same design porosity.The predominant failure mode of scaffolds during compression is a 45°shear fracture.At a porosity of 75%,the compression property of all scaffolds meets the compressive property requirements of cancellous bone,while bcc and G structures show relatively better compression property.After immersion in Hank's solution for 168 h,the B-2-75% pore structure scaffold exhibits severe localized corrosion,with fractures in partial pillar connections.In contrast,the G-3-75% pore structure scaffold mainly undergoes uniform corrosion,maintaining structural integrity,and its corrosion rate and loss of compressive properties are less than those of the B-2-75%structure.After comparison,the G-pore structure scaffold is preferred.展开更多
Pyridazine has garnered increasing attention as a privileged scaffold and bioisosterism in drug discovery due to its unique structural characteristics.It can serve as a hydrogen bond acceptor when interacting with rec...Pyridazine has garnered increasing attention as a privileged scaffold and bioisosterism in drug discovery due to its unique structural characteristics.It can serve as a hydrogen bond acceptor when interacting with receptors due to its two adjacent nitrogen atoms.Upon conversion to pyridazinone,it exhibits the ability to act as both a hydrogen bond acceptor and donor,showcasing its versatility.This inherent flexibility has prompted extensive research exploring its bioactivity in pesticides and pharmaceuticals.In order to promote the development of pyridazine-based pesticides,this review provides a comprehensive summary of advancements for pyridazine-based pesticides on herbicidal(36.9%),insecticidal(26.2%),antifungal and antibacterial(24.6%),plant growth regulatory(10.8%),and antiviral activities(1.5%)from2000 to 2024.It serves as an invaluable reference and source of inspiration for agricultural scientists conducting future research.展开更多
The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel...The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.展开更多
Metallic scaffolds with lightweight,low elastic modulus,and high energy-absorbing capacity are widely utilized in industrial applications but usually require post-heat treatment to enhance their comprehen-sive mechani...Metallic scaffolds with lightweight,low elastic modulus,and high energy-absorbing capacity are widely utilized in industrial applications but usually require post-heat treatment to enhance their comprehen-sive mechanical properties.However,it is unclear how to utilize the impact ofβ-Nb on the surrounding matrix for NiTiNb ternary alloys to achieve strength-ductility-superelasticity enhancement.Here,we pre-pared rhomboidal dodecahedral NiTiNb porous scaffolds with a porosity of 85.9%by additive manufac-turing.Subsequently,annealing treatment was employed to drastically reduce the phase transformation temperatures and expand the thermal hysteresis.Interestingly,the 850℃ annealed scaffold exhibited exceeding double compressive strength of the as-built sample,with a remarkable improvement in ductil-ity and superelasticity.From the microstructure perspective,high-temperature annealing caused a further eutectic reaction of the unmelted Nb particles with the NiTi matrix and the transformation of mesh-likeβ-Nb into dispersedly distributed sphericalβ-Nb particles.The microstructure evolution after defor-mation indicated that stress-induced martensitic transformation occurred in the matrix away from the NiTi-Nb eutectic region whereas almost no martensite formed nearbyβ-Nb particles.Atom probe tomog-raphy characterization revealed an element diffusion zone in several nanometers surrounding theβ-Nb particle,where the substitution of Nb with Ti led to a higher Ni:Ti atomic ratio,lowering transforma-tion temperatures.Molecular dynamics simulations illustrated thatβ-Nb particles can not only entangle dislocations internally,acting as reinforcements but also hinder the twin growth,contributing to strain hardening.This work elucidates the influence ofβ-Nb particles on the deformation mechanism of the NiTi-Nb eutectic region through in-depth atomic-scale investigation,which can provide inspiration for the improvement of comprehensive mechanical properties of NiTiNb alloys.展开更多
Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffol...Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.展开更多
Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.T...Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.This study proposes a sinusoidal-based lattice structure for an ultralow and widely tunable modulus design,aiming to match diverse bone tissue requirements and enhance biomechanical compatibility.Parametric modeling and finite element analysis were used to evaluate the performance of this structure.Results show that,within the design range suitable for bone growth,the elastic modulus of this lattice structure is tunable over a wide range,from 0.09 to 32.67 GPa,outperforming existing porous structures.The lowest value closely matched the minimum mechanical properties of human cancellous bone among porous structures.Moreover,the structure exhibited distinct anisotropic characteristics,allowing for directional design based on mechanical requirements.The structure’s permeability ranged from 1.19×10^(-8) m^(2) to 2.3×10^(-7) m^(2),making it highly compatible with human cancellous bone and meeting the requirements of orthopedic implants.Samples with porosities ranging from 46% to 87% were successfully fabricated using powder bed fusion additive manufacturing,validating the simulation predictions.This tunable low-modulus lattice structure provides a novel approach for developing personalized orthopedic implants,particularly for patients with specialized needs such as osteoporosis,and can potentially enhance biomechanical compatibility and long-term stability.展开更多
Imaging detection of interlinked dual proteases is imperative for precise tumor imaging,which remains challenging due to limited modification position of specific substrate and possible steric hindrance.Herein,we have...Imaging detection of interlinked dual proteases is imperative for precise tumor imaging,which remains challenging due to limited modification position of specific substrate and possible steric hindrance.Herein,we have developed a unimolecular chemiluminescent probe(LGP-CL)tandemly activated by two proteases interlinked with liver cancer to achieve precise tumor imaging.Probe LGP-CL consists of a phenoxy-dioxetane scaffold caged by a tripeptide substrate(LGP,leucine-glycine-proline)as the sensing layer,which can be cleaved sequentially by aminopeptidase N(APN)and dipeptidyl peptidase IV(DPPIV)to turn on a strong chemiluminescent signal,and silenced by specific inhibitor of each enzyme,which accounts for an integrated logic gate(AND,OR and INHIBIT).The successful cleavage of dual proteases on the metabolic site depends on the proper structure of the tripeptide substrate,as confirmed by two probes design.Probe LGP-CL(LGP as the substrate)enables the excellent“dual-lock-dual-key”fit with a382-fold enhancement of chemiluminescent emission while no obvious signal is observed by using GPLCL(GPL as the substrate).By virtue of its rapid response(several minutes),high sensitivity and good cell viability,probe LGP-CL has been utilized to evaluate upregulated levels of proteases in vitro and in living systems,especially to distinguish liver tumor cells(Hep G2)from others(LO_(2),MCF-7,MCF-10a and RAW264.7).Overall,the newly developed CL probe may facilitate rapid investigation into the role played by proteases in liver diseases,enabling timely selection appropriate treatment.Therefore,our work not only sheds light on the rational design of optical probes for dual protease imaging,but provides a promising tool for clinical diagnosis and even drug discovery.展开更多
Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects w...Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.展开更多
Natural bones exhibit a substantial recoverable strain(ε_(rec))of 2%-4%and vary in mechanical and mass transfer properties across different body regions.Integrating these attributes is essential for the functionality...Natural bones exhibit a substantial recoverable strain(ε_(rec))of 2%-4%and vary in mechanical and mass transfer properties across different body regions.Integrating these attributes is essential for the functionality and therapeutic efficacy of metallic scaffolds used in bone defect treatment.This study presents innovative superelastic nickel-titanium(NiTi)scaffolds with a remarkable maximumε_(rec)of 6%-7%and extensive tuneability in elastic modulus,cyclic stress,compressive strength,specific damping capacity,and permeability.These impressive performance integrations are attributed to carefully designed structures featuring stable austenite phases with hierarchical micro structures and gyroid-sheet macro structures.Physical experiments and computational simulations illustrate that this unique structure combination promotes martensitic transformation during deformation and allows the tuning of mechanical and mass transfer properties without compromising superelasticity.The deformationrecoverable and performance-tuneable NiTi scaffolds are more adaptive than their conventional counterparts,offering a versatile solution for diverse bone implantation needs.In addition to scaffold applications,this study provides valuable insights for developing advanced multifunctional metamaterials applicable in other fields.展开更多
文摘EFL preservice teachers ’ research efficacy, as perceived competence to perform tasks in research, is crucial to their research engagement. This autobiographical narrative inquiry investigates the contribution of scaffolded research practice to a female EFL preservice teacher ’s research efficacy.The data were collected through conversations, notes, journals, and portfolios. The findings suggest that teacher research efficacy was pliable through scaffolded research practice. It emerged gradually over time, in different places with social and personal interaction. The factors contributing to the emerging research efficacy were: teacher educators ’ support, peers ’ support,and research participation. The study sheds light on teacher educators and EFL preservice teachers,with the intention of establishing an inquiry-based pedagogy for M.Ed. programs.
基金supported by the National Key R&D Program of China(2016YFA0202602,2016YFA0202603)the National Natural Science Foundation of China(U1663225)+1 种基金the 111 national project(Grant No.B20002)from Ministry of Science and Technologythe Ministry of Education and Sinopec Ministry of Science and Technology Basic Prospective Research Project(218025-9)。
文摘Supercapacitor-like Na-ion batteries have attracted much attention due to the high energy density of batteries and power density of capacitors.Titanium dioxide(TiO_(2)),is a promising anode material.Its performance is however seriously hindered by its low electrical conductivity and the sluggish diffusion of sodium ions(Na^(+))in the TiO_(2)matrix.Herein,this work combines porous TiO_(2)nanocubes with carbon nanotubes(CNTs)to enhance the electrical conductivity and accelerate Na^(+)diffusivity for Na-ion batteries(NIBs).In this composite,an interwoven scaffolded TiO_(2)/CNTs framework is formed to provide abundant channels and shorter diffusion pathways for electrons and ions.The in-situ X-ray diffraction and cyclic voltammetry confirm the low strain and superior transport kinetics in Na^(+)intercalation/extraction processes.In addition,the chemically bonded TiO_(2)/CNTs hybrid provides a more feasible channel for Na^(+)insertion/extraction with a much lower energy barrier.Consequently,the TiO_(2)/CNTs composite exhibits excellent electrochemical performance with a capacity of 223.4 m Ah g^(-1)at 1 C and a capacity of 142.8 m Ah g^(-1)at 10 C(3.35 A g^(-1)).The work here reveals that the combination of active materials with CNTs can largely improve the utilization efficiency and enhance their sodium storage.
基金supported by the Russian state-funded project for ICBFM SB RAS(grant number 125012300656-5)。
文摘Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.
基金Financial support from Beijing Natural Science Foundation(No.7232283)。
文摘From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82173699 and 32200531)Shanghai Jiao Tong University Trans-Med Awards Research,China(STAR Project No.:20230101)Shanghai Science and Technol-ogy Commission,China(Grant No.:23DZ2290600).
文摘Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC_(50))of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal“dead ends”and“safe bets”for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogeneoxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)the Shanxi Provincial Key Medical Scientific Research Project(No.2020XM06)+2 种基金the Shanxi Provincial Basic Research Project(Nos.202103021221006,20210302123040,and 202103021223069)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.
基金supported by the National Natural Science Foundation of China(No.82272297).
文摘Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.
基金supported by the National Natural Science Foundation of China(Grant No.52473121,52403370 and 52221006)Fundamental Research Funds for the Central Universities(buctrc202020,buctrc202312).
文摘The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.
基金the National Key Research and Development Program of China(Grant No.2023YFC2412600)the National Natural Science Foundation of China(Grant No.51971171)for financially supporting this work.
文摘Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength(σ_(cf))of the resultant implants,thereby shortening their service lifes-pan.To resolve this issue,in the present,a step-wise graded porous Ti-6Al-7Nb scaffold was additively manufactured on optimally surface mechanical attrition treated(SMATed)Ti-6Al-7Nb(specifically de-noted as S-Ti6Al7Nb)using laser powder bed fusion(PBF)technology.The microstructure,bond strength,residual stress distribution,and corrosion fatigue behavior of porous scaffolds modified S-Ti6Al7Nb were investigated and compared with those of mechanically polished Ti-6Al-7Nb(P-Ti6Al7Nb),S-Ti6Al7Nb,and porous scaffolds modified P-Ti6Al7Nb.Results showed that corrosion fatigue of porous scaffolds modi-fied Ti-6Al-7Nb was propagation controlled.Moreover,the crack propagation behavior in the PBF scaf-fold’s fusion zone(FZ)and heat-affected zone(HAZ),exhibiting insensitivity to the microstructural con-figurations characterized by columnar prior-βgrain(PBG)boundaries and acicularα''martensites,cou-pled with the PBF-induced residual tensile stresses in these regions,resulted in a considerable decrease inσ_(cf) for porous scaffolds modified P-Ti6Al7Nb compared to P-Ti6Al7Nb.In contrast,step-wise graded porous scaffold-modified S-Ti6Al7Nb demonstrated an improvedσ_(cf) which was even higher than that of P-Ti6Al7Nb.Such an advancement in corrosion fatigue strength is primarily attributed to the presence of residual compressive stresses within the underlying S-Ti6Al7Nb substrate,extending beyond FZ and HAZ.These stresses increased the crack propagation threshold,leading to crack deflection/branching and increased crack-path tortuosity,thereby synergistically markedly enhancing the crack propagation resis-tance of porous scaffolds modified S-Ti6Al7Nb.
基金supported by the Innovative Research Group Project of the National Natural Science Foundation of China(T2121004)Key Programme(52235007)National Outstanding Youth Foundation of China(52325504).
文摘Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.
文摘Introduction It is necessary for an ideal bioceramic scaffold to have a suitable structure.The structure can affect the mechanical properties of the scaffold(i.e.,elastic modulus and compressive strength)and the biological properties of the scaffold(i.e.,degradability and cell growth rate).Lattice structure is a kind of periodic porous structure,which has some advantages of light weight and high strength,and is widely used in the preparation of bioceramic scaffolders.For the structure of the scaffold,high porosity and large pore size are important for bone growth,bone integration and promoting good mechanical interlocking between neighboring bones and the scaffold.However,scaffolds with a high porosity often lack mechanical strength.In addition,different parts of the bone have different structural requirements.In this paper,scaffolds with a non-uniform structure or a hierarchical structure were designed,with loose and porous exterior to facilitate cell adhesion,osteogenic differentiation and vascularization as well as relatively dense interior to provide sufficient mechanical support for bone repair.Methods In this work,composite ceramics scaffolds with 10%akermanite content were prepared by DLP technology.The scaffold had a high porosity outside to promote the growth of bone tissue,and a low porosity inside to withstand external forces.The compressive strength,fracture form,in-vitro degradation performance and bioactivity of graded bioceramic scaffolds were investigated.The models of scaffolds were imported into the DLP printer with a 405 nm light.The samples were printed with the intensity of 8 mJ/cm^(2)and a layer thickness of 50μm.Finally,the ceramic samples were sintered at 1100℃.The degradability of the hierarchical gyroid bioceramic scaffolds was evaluated through immersion in Tris-HCl solution and SBF solution at a ratio of 200 mL/g.The bioactivity of bioceramic was obtained via immersing them in SBF solution for two weeks.The concentrations of calcium,phosphate,silicon,and magnesium ions in the soaking solution were determined by an inductively coupled plasma optical emission spectrometer.Results and discussion In this work,a hierarchical Gyroid structure HA-AK10 scaffold(sintered at 1100℃)with a radial internal porosity of 50%and an external porosity of 70%is prepared,and the influence of structural form on the compressive strength and degradation performance of the scaffold is investigated.The biological activity of the bioceramics in vitro is also verified.The mechanical simulation results show that the stress distribution corresponds to the porosity distribution of the structure,and the low porosity is larger and the overall stress concentration phenomenon does not appear.After soaking in SBF solution,Si—OH is firstly formed on the surface of bioceramics,and then silicon gel layer is produced due to the presence of calcium and silicon ions.The silicon gel layer is dissociated into negatively charged groups under alkaline environment secondary adsorption of calcium ions and phosphate ions,forming amorphous calcium phosphate,and finally amorphous calcium phosphate crystals and adsorption of carbonate ions,forming carbonate hydroxyapatite.This indicates that the composite bioceramics have a good biological activity in-vitro and can provide a good environment for the growth of bone cells.A hierarchical Gyroid ceramic scaffold with a bone geometry is prepared via applying the hierarchical structure to the bone contour scaffold.The maximum load capacity of the hierarchical Gyroid ceramic scaffold is 8 times that of the uniform structure.Conclusions The hierarchical structure scaffold designed had good overall compressive performance,good degradation performance,and still maintained a good mechanical stability during degradation.In addition,in-vitro biological experimental results showed that the surface graded composite scaffold could have a good in-vitro biological activity and provide a good environment for bone cells.Compared to the heterosexual structure,the graded scaffold had greater mechanical properties.
基金Science and Technology Planning Project of Inner Mongolia Science and Technology Department(2022YFSH0021)Key Research and Development Program of Shaanxi Province(2024SF2-GJHX-14,2021SF-296)。
文摘Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser melting.Their forming quality,compression mechanical properties,and degradation behavior were investigated.Results indicate that the fabricated scaffolds exhibit good dimensional accuracy,and the surface chemical polishing treatment significantly improves the forming quality and reduces porosity error in porous scaffolds.Compared to the ones with rod structures(bcc,RD),the scaffolds with surface structures(G,P)have less powder particle adhesion.The G porous scaffold exhibits the best forming quality for the same design porosity.The predominant failure mode of scaffolds during compression is a 45°shear fracture.At a porosity of 75%,the compression property of all scaffolds meets the compressive property requirements of cancellous bone,while bcc and G structures show relatively better compression property.After immersion in Hank's solution for 168 h,the B-2-75% pore structure scaffold exhibits severe localized corrosion,with fractures in partial pillar connections.In contrast,the G-3-75% pore structure scaffold mainly undergoes uniform corrosion,maintaining structural integrity,and its corrosion rate and loss of compressive properties are less than those of the B-2-75%structure.After comparison,the G-pore structure scaffold is preferred.
基金the financial support from the National Key Research and Development Program of China(No.2021YFD1700102)the National Natural Science Foundation of China(No.32472608)+3 种基金the Guizhou Provincial Fundation for Excellent Scholars Program(No.GCC[2023]069)the Central Government Guides Local Science and Technology Development Fund Projects(No.Qiankehezhongyindi[2024]007)the Guizhou Province Program of Major Scientific and Technological(No.Qiankehechengguo[2024]zhongda007)the Central Government Guides Local Science and Technology Development Fund Projects(No.Qiankehezhongyindi(2023)001)。
文摘Pyridazine has garnered increasing attention as a privileged scaffold and bioisosterism in drug discovery due to its unique structural characteristics.It can serve as a hydrogen bond acceptor when interacting with receptors due to its two adjacent nitrogen atoms.Upon conversion to pyridazinone,it exhibits the ability to act as both a hydrogen bond acceptor and donor,showcasing its versatility.This inherent flexibility has prompted extensive research exploring its bioactivity in pesticides and pharmaceuticals.In order to promote the development of pyridazine-based pesticides,this review provides a comprehensive summary of advancements for pyridazine-based pesticides on herbicidal(36.9%),insecticidal(26.2%),antifungal and antibacterial(24.6%),plant growth regulatory(10.8%),and antiviral activities(1.5%)from2000 to 2024.It serves as an invaluable reference and source of inspiration for agricultural scientists conducting future research.
基金supported by the National Key Research and Development Program of China(2019YFA0905200).
文摘The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.
基金financial supports of National Natural Science Foundation of China under Grant Nos.52274387 and 52311530772.
文摘Metallic scaffolds with lightweight,low elastic modulus,and high energy-absorbing capacity are widely utilized in industrial applications but usually require post-heat treatment to enhance their comprehen-sive mechanical properties.However,it is unclear how to utilize the impact ofβ-Nb on the surrounding matrix for NiTiNb ternary alloys to achieve strength-ductility-superelasticity enhancement.Here,we pre-pared rhomboidal dodecahedral NiTiNb porous scaffolds with a porosity of 85.9%by additive manufac-turing.Subsequently,annealing treatment was employed to drastically reduce the phase transformation temperatures and expand the thermal hysteresis.Interestingly,the 850℃ annealed scaffold exhibited exceeding double compressive strength of the as-built sample,with a remarkable improvement in ductil-ity and superelasticity.From the microstructure perspective,high-temperature annealing caused a further eutectic reaction of the unmelted Nb particles with the NiTi matrix and the transformation of mesh-likeβ-Nb into dispersedly distributed sphericalβ-Nb particles.The microstructure evolution after defor-mation indicated that stress-induced martensitic transformation occurred in the matrix away from the NiTi-Nb eutectic region whereas almost no martensite formed nearbyβ-Nb particles.Atom probe tomog-raphy characterization revealed an element diffusion zone in several nanometers surrounding theβ-Nb particle,where the substitution of Nb with Ti led to a higher Ni:Ti atomic ratio,lowering transforma-tion temperatures.Molecular dynamics simulations illustrated thatβ-Nb particles can not only entangle dislocations internally,acting as reinforcements but also hinder the twin growth,contributing to strain hardening.This work elucidates the influence ofβ-Nb particles on the deformation mechanism of the NiTi-Nb eutectic region through in-depth atomic-scale investigation,which can provide inspiration for the improvement of comprehensive mechanical properties of NiTiNb alloys.
基金supported by grants from the China Postdoctoral Science Foundation(Nos.2022TQ0397,2022MD723744,2022M710564,2022M720603)Natural Science Foundation of China(Nos.82272553,82102571,81974346,8210257,82472404)+8 种基金Chongqing Municipal Medical Youth Talent Support Program,Chongqing,China(No.YXQN202408)Natural Science Foundation of Chongqing,China(Nos.CSTB2022NSCQ-MSX0089,CSTB2022NSCQ-MSX0104,CSTB2024NSCQMSX0532)Joint Medical Research Project of Health Commission&Science and Technology Bureau of Chongqing,China(No.2024QNXM032)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(No.2023ZYD0071)National Natural Science Foundation of Sichuan(No.24NSFSC1274)Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee,Chongqing,China(Nos.CYS22389,CYB240224)National Natural Science Foundation of Sichuan(No.2024NSFSC0678)Research Project of the Affiliated Hospital of North Sichuan Medical College(Nos.2023ZD002,2023-2ZD001,2024JB001)Disciplines Construction Program of The Third Affiliated Hospital of Chongqing Medical University(Nos.KY23035,KY23041).
文摘Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.
基金supported by National Key R&D Program of China(Grant No.2022YFB4600500)Fundamental Research Funds for the Central Universities,and the Program for Innovation Team of Shaanxi Province(Grant No.2023-CX-TD-17).
文摘Porous designs effectively reduce stress shielding in metallic orthopedic implants.However,current porous structures often fail to adequately meet the needs of patients with osteoporosis and low-modulus body regions.This study proposes a sinusoidal-based lattice structure for an ultralow and widely tunable modulus design,aiming to match diverse bone tissue requirements and enhance biomechanical compatibility.Parametric modeling and finite element analysis were used to evaluate the performance of this structure.Results show that,within the design range suitable for bone growth,the elastic modulus of this lattice structure is tunable over a wide range,from 0.09 to 32.67 GPa,outperforming existing porous structures.The lowest value closely matched the minimum mechanical properties of human cancellous bone among porous structures.Moreover,the structure exhibited distinct anisotropic characteristics,allowing for directional design based on mechanical requirements.The structure’s permeability ranged from 1.19×10^(-8) m^(2) to 2.3×10^(-7) m^(2),making it highly compatible with human cancellous bone and meeting the requirements of orthopedic implants.Samples with porosities ranging from 46% to 87% were successfully fabricated using powder bed fusion additive manufacturing,validating the simulation predictions.This tunable low-modulus lattice structure provides a novel approach for developing personalized orthopedic implants,particularly for patients with specialized needs such as osteoporosis,and can potentially enhance biomechanical compatibility and long-term stability.
基金financial support by National Key R&D Program of China,MOST(No.2023YFC2510000)Shanghai Science and Technology(No.21N31900500)+2 种基金Shanghai Municipal Health Commission Project(No.202140016)Training Program for Outstanding Young Medical and Pharmaceutical Talents of Minhang District Health System(No.mwyjyx08)the Project of Basic Medicine funded by Fudan-Minhang Health Consortium(Nos.2021MHJC10 and 2023FM09)。
文摘Imaging detection of interlinked dual proteases is imperative for precise tumor imaging,which remains challenging due to limited modification position of specific substrate and possible steric hindrance.Herein,we have developed a unimolecular chemiluminescent probe(LGP-CL)tandemly activated by two proteases interlinked with liver cancer to achieve precise tumor imaging.Probe LGP-CL consists of a phenoxy-dioxetane scaffold caged by a tripeptide substrate(LGP,leucine-glycine-proline)as the sensing layer,which can be cleaved sequentially by aminopeptidase N(APN)and dipeptidyl peptidase IV(DPPIV)to turn on a strong chemiluminescent signal,and silenced by specific inhibitor of each enzyme,which accounts for an integrated logic gate(AND,OR and INHIBIT).The successful cleavage of dual proteases on the metabolic site depends on the proper structure of the tripeptide substrate,as confirmed by two probes design.Probe LGP-CL(LGP as the substrate)enables the excellent“dual-lock-dual-key”fit with a382-fold enhancement of chemiluminescent emission while no obvious signal is observed by using GPLCL(GPL as the substrate).By virtue of its rapid response(several minutes),high sensitivity and good cell viability,probe LGP-CL has been utilized to evaluate upregulated levels of proteases in vitro and in living systems,especially to distinguish liver tumor cells(Hep G2)from others(LO_(2),MCF-7,MCF-10a and RAW264.7).Overall,the newly developed CL probe may facilitate rapid investigation into the role played by proteases in liver diseases,enabling timely selection appropriate treatment.Therefore,our work not only sheds light on the rational design of optical probes for dual protease imaging,but provides a promising tool for clinical diagnosis and even drug discovery.
基金supported by the National Natural Science Foundation of China(No.82202450).
文摘Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.
基金supported by the RGC Theme-based Research Scheme Ao E/M-402/20National Natural Science Foundation of China/Hong Kong Research Grants Council Joint Research Scheme(Project No.N_City U151/23)+3 种基金Hong Kong JLFSRGC-Joint Laboratory Funding Scheme(Grant No.JLFS/E102/24)Guangdong Province Science and Technology Plan Project 2023B1212120008Shenzhen Science and Technology Project(Project No:ZDSYS201602291653165)the IMR-City U Joint Laboratory of Nanomaterials&Nanomechanics and Guangdong-Hong Kong Joint Laboratory of Modern Surface Engineering Technology。
文摘Natural bones exhibit a substantial recoverable strain(ε_(rec))of 2%-4%and vary in mechanical and mass transfer properties across different body regions.Integrating these attributes is essential for the functionality and therapeutic efficacy of metallic scaffolds used in bone defect treatment.This study presents innovative superelastic nickel-titanium(NiTi)scaffolds with a remarkable maximumε_(rec)of 6%-7%and extensive tuneability in elastic modulus,cyclic stress,compressive strength,specific damping capacity,and permeability.These impressive performance integrations are attributed to carefully designed structures featuring stable austenite phases with hierarchical micro structures and gyroid-sheet macro structures.Physical experiments and computational simulations illustrate that this unique structure combination promotes martensitic transformation during deformation and allows the tuning of mechanical and mass transfer properties without compromising superelasticity.The deformationrecoverable and performance-tuneable NiTi scaffolds are more adaptive than their conventional counterparts,offering a versatile solution for diverse bone implantation needs.In addition to scaffold applications,this study provides valuable insights for developing advanced multifunctional metamaterials applicable in other fields.
